AMERICAN DIABETES ASSOCIATION-SELF-ASSESSMENT … Diabetes Association Self... · AMERICAN DIABETES...
Transcript of AMERICAN DIABETES ASSOCIATION-SELF-ASSESSMENT … Diabetes Association Self... · AMERICAN DIABETES...
AMERICAN DIABETES ASSOCIATION-SELF-ASSESSMENT PROGRAM:
CARDIOMETABOLIC RISK
Target Audience
All health care professionals involved in treating individuals with, or at risk for, diabetes, including
physicians, physician assistants, nurses, nurse practitioners, dietitians, pharmacists, and other health care
professionals.
Learning Objectives
I. Identify cardiometabolic risk (CMR) factors associated with the pathophysiology of cardiovascular
(CV) disease in persons with, or at risk for, prediabetes or type 2 diabetes.
II. Implement screening strategies for individuals with CMR into clinical practice to promote early
detection and prevention of prediabetes or diabetes.
III. Discuss how preventing CMR factors can positively impact CV health in persons with, or at risk
for, prediabetes or type 2 diabetes.
IV. List treatment options and define goals of treatment directed toward CMR factors.
V. Incorporate into clinical practice evidence‐based data from clinical trials and recommendations
from clinical practice guidelines toward the optimal management of individuals with CMR.
Abbreviations used throughout this program:
A1c=glycosylated hemoglobin A1c
ACC=American College of Cardiology
ACCOMPLISH=Avoiding Cardiovascular Events in Combination Therapy in Patients Living with
Systolic Hypertension
ACCORD=Action to Control Cardiovascular Risk in Diabetes
ACE=angiotensin converting enzyme
AHA=American Heart Association
AHEAD=Action for Health in Diabetes
ARB=angiotensin receptor blocker
Association=American Diabetes Association
ATP-III=Adult Treatment Panel
BMI=body mass index
BP=blood pressure
CMR=cardiometabolic risk
CABG=coronary arterial bypass graft
CRP=c-reactive protein
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CV=cardiovascular
DASH=Dietary Approaches to Stop Hypertension
DBP=diastolic blood pressure
DPP=Diabetes Prevention Program
DSME= diabetes self-management education
DSMS=diabetes self-management support
DSE=diabetes support education
FDA=Food and Drug Administration
FPG=fasting plasma glucose
GDM=gestational diabetes mellitus
HDL-C=high-density lipoprotein cholesterol
IFG=impaired fasting glucose
IGT=impaired glucose tolerance
INSPIRE ME IAA=International Study of the Prediction of Intra-Abdominal Adiposity and its
Relationship with CMR/Intra-Abdominal Adiposity
ILI=intensive lifestyle intervention
IPG=impaired fasting glucose
LDL-C=low-density lipoprotein cholesterol
NHANES=National Health and Nutrition Examination Survey
OHS=obesity-hypoventilation syndrome
OGTT=oral glucose tolerance test
OmniHeart=Optimal Macronutrient Intake Trial for Heart Health
OSA=obstructive sleep apnea
PCI=percutaneous coronary intervention
PTDS=post-traumatic stress disorder
REMS= risk evaluation and mitigation strategy
SBP=systolic blood pressure
SSB=sugar-sweetened beverages
TZD=thiazolidinedione
TOS=The Obesity Society
U.S.=United States
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VLDL=very low-density lipoprotein cholesterol
WHR=waist-to-hip ratio
WHtR=waist-to-height ratio
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CASE STUDY #1
HT, a 39-year old Japanese-American male, comes in for a routine check-up. In reviewing his medical
record, you note that he has had difficulty controlling his blood glucose over the past 20 years, with FPG
levels fluctuating between 95 mg/dL and 115 mg/dL. Over that time period, you have consistently
counseled him to increase his level of exercise, but his work schedule was so erratic that he did not. In
addition, his occupation (actor) required him to intermittently add excessive weight (30-40 pounds) and
then is forced to lose that weight in a short amount of time.
Physical exam: height, 5’10” (177.8 cm); weight, 180 lbs (84 kg); BMI, 25.8 kg/m2; waist circumference,
38 inches (96.5 cm); SBP, 126 mmHg; DBP, 80 mmHg (average of 3 readings).
Social history: 1-2 glasses of wine a day; denies tobacco use; no structured exercise program, although his
work does involve physical activity at times.
Lab results (within the past week): A1c, 6.0%; fasting blood glucose, 108 mg/dL; total cholesterol, 190
mg/dL; LDL-C, 124mg/dL; HDL-C, 34 mg/dL; triglycerides, 160 mg/dL
Medications: None
Assessment: HT has prediabetes, but is otherwise is healthy and in no acute distress.
Questions 1-15
1. IFG is a condition in which the FPG level is between:
A. 75 and 100 mg/dL
B. 100 and 125 mg/dL
C. 125 and 150 mg/dL
D. 140 and 199 mg/dL
E. >200 mg/dL
Answer: B
Rationale:
Individuals with IFG and/or IGT have been referred to as having prediabetes, indicating the relatively
high risk for the future development of diabetes. By definition, IFG is a condition in which FPG levels
range between 100 mg/dL (5.6 mmol/L) and 125 mg/dL (6.9 mmol/L) after an 8 to 12 hour fast. IGT is
defined as having 2-hour plasma glucose values from an OGTT of 140 mg/dL (7.8 mmol/L) to 199
mg/dL (11.0 mmol/L). If the 2-hour blood glucose rises to 200 mg/dl or above, a person has diabetes.
For A1c, clinical research studies that used this measurement to predict the progression to diabetes
demonstrated a strong, continuous association between A1c and subsequent diabetes. An A1c range of
6.0–6.5% had a 5-year risk of developing diabetes between 25 to 50%, with a relative risk 20 times higher
compared with an A1c of 5.0%. Other analyses suggest that an A1c of 5.7% is associated with diabetes
risk similar to that in the high-risk participants in the Diabetes Prevention Program (DPP). The American
Diabetes Association’s Standards of Care state that it is reasonable to consider an A1c range of 5.7–6.4%
as identifying individuals with prediabetes. Thus, HT’s A1c of 6.3% meets the criteria for prediabetes.
Reference(s):
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Ackermann RT, Cheng YJ, Williamson DF, Gregg EW. Identifying adults at high risk for diabetes and
cardiovascular disease using hemoglobin A1c National Health and Nutrition Examination Survey 2005-
2006. Am J Prev Med. 2011;40:11–17.
Zhang X, Gregg EW, Williamson DF, et al. A1C level and future risk of diabetes: a systematic review.
Diabetes Care. 2010;33:1665–1673.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
2. Prediabetes is a state in which:
A. One’s blood glucose level falls within the normal range.
B. A patient has IFG and/or IGT.
C. One’s blood glucose level is higher than normal, but not yet high enough to be diagnostic of diabetes.
D. Both b and c
E. All of the above
Answer: D
Rationale:
Recognizing clinical signs in individuals at risk for developing diabetes is a key to prevention. Two signs
that should alert clinicians are higher than normal blood glucose levels, based upon IFG, IGT, and/or an
elevated A1c level. Although these levels may not high enough to be classified as diabetes, many
clinicians disregard their significance. IFG and IGT should be viewed as risk factors for diabetes as well
as CV disease rather than clinical entities, as they are associated with obesity (especially abdominal or
visceral obesity), atherogenic dyslipidemia with high triglycerides and/or low HDL-C, and hypertension.
Thus, there is a relatively high risk for the future development of diabetes for individuals with IFG, IGT,
and/or elevated A1c despite not having diabetes by a clinical definition. This condition is called
prediabetes.
Reference(s):
Ferrannini E, Balkau B, Coppack SW, et al; RISC Investigators. Insulin resistance, insulin response, and
obesity as indicators of metabolic risk. J Clin Endocrinol Metab. 2007;92:2885-2892.
CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes
in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, CDC; 2011.
Available at http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed November 3, 2013.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care.
2014;37 Suppl 1:S81-90.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
3. Insulin resistance is a key feature in type 2 diabetes, as well as:
A. Dyslipidemia
B. Endothelial dysfunction
C. Obesity
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D. Acanthosis nigricans
E. All of the above
Answer: E
Rationale:
Insulin resistance is characterized by the impaired function of insulin to stimulate glucose disposal in
peripheral tissues and suppress hepatic glucose production. Insulin resistance is a key feature of type 2
diabetes, as well as dyslipidemia, obesity, hypertension, and endothelial dysfunction.
Reference(s):
Ferrannini E, Balkau B, Coppack SW, et al; RISC Investigators. Insulin resistance, insulin response, and
obesity as indicators of metabolic risk. J Clin Endocrinol Metab. 2007;92:2885-2892.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
4. Which of the following statement(s) are true?
A. CV disease risk escalates with increasing hyperglycemia and insulin resistance, which may occur
long before the clinical diagnosis of diabetes.
B. IFG confers a much greater risk of coronary heart disease, CV disease, and overall mortality than the
presence of the metabolic syndrome.
C. CMR only includes the major components of the metabolic syndrome and no other factors that affect
risk, such as lifestyle and genetic factors.
D. A and B above.
E. A and C above.
Answer: A
Rationale:
CMR is preferred term to denote both the cluster of risk factors traditionally known as metabolic
syndrome, which includes traditional parameters of CV disease risk (waist circumference, triglycerides,
HDL-C, blood pressure, IFG), as well as risk markers resulting from abdominal obesity (certain cytokines
and adipokines). The term captures all risk related to the metabolic changes associated with CV disease
and not just those fitting the metabolic syndrome definition. CV risk factors, such as hypertension,
diabetes, elevated cholesterol and atherogenic dyslipidemia, and cigarette smoking promote oxidative
stress to cause endothelial dysfunction, initiating a cascade of events. These events include alterations in
vasoactive mediators, inflammatory responses, and vascular remodeling, which culminate in target-organ
damage. Evidence indicates that these processes begin earlier in life than previously recognized,
indicating that CV disease occurs over decades, long before the clinical diagnosis of diabetes.
Reference(s)
Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical
evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors
through stable coronary artery disease). Circulation. 2006;114:2850-2870.
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Balkau B, Deanfield JE, Després JP, et al. International Day for the Evaluation of Abdominal Obesity
(IDEA): a study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000
primary care patients in 63 countries. Circulation. 2007;116:1942-1951.
5. The most common cause of acquired insulin resistance is:
A. BMI <23 kg/m2 without abdominal obesity
B. Abdominal (visceral) obesity
C. Increased subcutaneous fat deposition
D. CRP level <1.0 mg/L
E. FPG level <100 mg/dL
Answer: B
Rationale:
An important component of increased CMR is abdominal obesity (increased waist circumference), and is
caused by excess abdominal visceral fat. Approximately 85% of total adipose tissue mass is located
under the skin (subcutaneous fat), with the remainder, approximately 15%, being located within the
abdomen (intra-abdominal fat). The relative contribution of intra-abdominal fat mass to total body fat is
influenced by sex, age, race/ethnicity, physical activity, and total adiposity. The term “visceral fat” is
commonly used to describe intra-abdominal fat and includes both intraperitoneal fat (mesenteric and
omental fat), which drains directly into the portal circulation, and retroperitoneal fat, which drains into the
systemic circulation.
This excess visceral fat is more metabolically active than subcutaneous fat, has greater endocrine activity,
and causes greater adverse effect on metabolism and CV risk. Visceral fat also has a greater ability to
release cytokines and adipokines than subcutaneous fat. These cytokines and adipokines have an impact
on causing insulin resistance, elevating triglyceride and small-dense LDL-C levels, hyperinsulinemia, and
endothelial dysfunction, all of which can contribute to vascular damage. One study showed among
overweight/moderately obese men and women, after adjusting for BMI, increases in visceral adipose
tissue increased the risk for insulin resistance, whereas increases in subcutaneous adipose tissue decreased
the risk for insulin resistance.
A BMI of <25 kg/m2 is considered to be an optimal weight and not considered to be the most common
cause of insulin resistance, especially in the absence of abdominal obesity. CRP is a measurement of
inflammation and used to further evaluate underlying risk, but not a cause of insulin resistance. An
individual with a high-sensitivity-CRP level of <1.0 mg/L is considered at low risk.
Reference(s):
Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome.
Endocr Rev. 2000;21:697‐738.
Ballantyne CH, Nambi V. Markers of inflammation and their clinical significance. Atherosclerosis.
2005;6(suppl): 21-29.
Klein S, Allison DB, Heymsfield SB, et al; Association for Weight Management and Obesity Prevention;
NAASO; Obesity Society; American Society for Nutrition; American Diabetes Association. Waist
circumference and cardiometabolic risk: a consensus statement from Shaping America's Health:
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Association for Weight Management and Obesity Prevention; NAASO, the Obesity Society; the
American Society for Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647-
1652.
Cornier MA, Dabelea D, Hernandez TL, Lindstrom RC, Steig AJ, Stob NR, et al. The metabolic
syndrome. Endocr Rev. 2008;29:777–822.
McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral
depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011;96:E1756-1760.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
6. Excess fat within in the abdomen (visceral adiposity) is:
A. A traditional marker for CV disease risk
B. More strongly associated with CMR than overall weight or BMI
C. A less potent risk factor than BMI
D. Is less metabolically active than subcutaneous fat
E. A surrogate measure of increased insulin sensitivity
Answer: B
Rationale:
CMR comprises a cluster of risk factors that are good indicators of an individual’s overall risk for CV
disease and type 2 diabetes. CMR also includes visceral obesity and other markers not traditionally
considered in CV disease risk assessment. A more potent risk factor than BMI, excess fat within the
abdomen and other organs, as opposed to subcutaneous tissues, has been linked with glucose intolerance,
dyslipidemia, and hypertension, as well as insulin resistance. Visceral fat is more insulin resistant and
more metabolically active than subcutaneous fat and has been shown to release excess toxic cytokines,
proinflammatory molecules, and vasoactive hormones, as well as driving excess free fatty acids and
cortisol directly to the liver.
Reference(s):
Ferrannini E, Balkau B, Coppack SW, et al; RISC Investigators. Insulin resistance, insulin response, and
obesity as indicators of metabolic risk. J Clin Endocrinol Metab. 2007;92:2885-2892.
Smith JD, Borel AL, Nazare JA, et al. Visceral adipose tissue indicates the severity of cardiometabolic
risk in patients with and without type 2 diabetes: results from the INSPIRE ME IAA study. J Clin
Endocrinol Metab. 2012;97:1517-1525.
7. Which of the following is currently the most widely used index of abdominal (visceral) obesity?
A. BMI
B. Absolute waist circumference
C. A1c
D. Total cholesterol/HDL-C ratio
E. A and B above
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Answer: B
Rationale:
BMI is an index of general adiposity. Because waist measurement is more prone to errors than measuring
height and weight, it is recommended to use all three. BMI best illustrates an estimate of the level of
obesity, while waist measurement gives an estimate of visceral fat and risk of obesity-related diseases,
such as diabetes. The relationship between waist circumference and clinical outcomes is consistently
strong for diabetes risk, and waist circumference is a stronger predictor of diabetes than is BMI. But,
waist circumference can identify persons who are at greater CMR than those identified by BMI alone.
Beyond waist circumference, the waist-to-hip ratio is used to determine the severity of central obesity.
Although total cholesterol/HDL-C ratio is used as a marker for increased insulin resistance, it is not a
marker of visceral obesity.
The most recent ACC/AHA/TOS guidelines on obesity note that is not necessary to measure waist
circumference in patients with BMI >35, as this measurement will likely be elevated and it adds no
additional risk information. As an indication of increased CMR, these guidelines continue to recommend
using the current cutpoints: >35 inches (88 cm) for women and >40 inches (102 cm) for men. Thus, a
large waist circumference is a key surrogate measure of insulin resistance when assessing risk of incident
diabetes and CV disease.
Reference(s):
Yusuf S, Hawken S, Ounpuu S, et al; INTERHEART Study Investigators. Effect of potentially
modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study):
case-control study. Lancet. 2004;364:937–952.
Klein S, Allison DB, Heymsfield SB, et al; Association for Weight Management and Obesity Prevention;
NAASO; Obesity Society; American Society for Nutrition; American Diabetes Association. Waist
circumference and CMR: a consensus statement from shaping America's health: Association for Weight
Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for
Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647-1652.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
8. Based upon results from the from the International Study of the INSPIRE ME IAA study, what
was the impact of diabetes treatment for achieving the American Diabetes Association's
(Association’s) goals for HDL-C or triglycerides despite the presence of excess visceral adipose
tissue and liver fat?
A. Fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for
the two lipid parameters compared to patients with low visceral adipose tissue or liver fat
regardless of diabetes treatment.
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B. More patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for
the two lipid parameters compared to patients with low visceral adipose tissue or liver fat.
C. Fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for
HDL-C but not triglycerides compared to patients with low visceral adipose tissue or liver fat.
D. Fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s goals for
triglycerides but not HDL-C compared to patients with low visceral adipose tissue or liver fat.
E. None of the above
Answer: A
Rationale:
Both visceral adipose tissue and liver fat are strongly associated with insulin resistance and type 2
diabetes. In a cross-sectional analysis of baseline data (N = 3991) from the INSPIRE ME IAA study,
patients were divided into four groups: those without type 2 diabetes (n=1003 men, n=1027 women);
those with type 2 diabetes but not treated with diabetes medications (n=248 men, n=198 women); those
with type 2 diabetes and treated with diabetes medications but not yet using insulin (n=591 men, n=484
women), and those with type 2 diabetes and treated with insulin (n=233 men, n=207 women).
Results showed fewer patients with excess visceral adipose tissue or liver fat achieved the Association’s
goals for HDL-C or triglycerides compared to patients with low visceral adipose tissue or liver fat. Both
visceral adiposity (p = .02 men, p = .003 women) and liver fat (p = .0002 men, p = .0004 women) were
increased among patients who met fewer of the Association treatment criteria, regardless of type 2
diabetes treatment. Residual CMR exists among patients with type 2 diabetes characterized by elevated
VAT and LF.
Reference(s):
Smith J, Nazare JA, Borel AL, et al. Assessment of CMR and prevalence of meeting treatment guidelines
among patients with type 2 diabetes stratified according to their use of insulin and/or other diabetic
medications: results from INSPIRE ME IAA. Diabetes Obes Metab. 2013;15:629-641.
9. Which of the following is INCORRECT regarding how to measure waist circumference?
A. There is a uniformly-accepted approach when measuring waist circumference.
B. Measurement should be made around an individuals’ bare midriff, after they exhale while standing
without shoes, both feet touching, and arms hanging freely.
C. The measuring tape should be made of a material that is not easily stretched.
D. The tape should be placed perpendicular to the long axis of the body and horizontal to the floor and
applied with sufficient tension to conform to the measurement surface.
E. All of the above.
Answer: A
Rationale:
Waist circumference measurements should be made around a patient's bare midriff, after the patient
exhales while standing without shoes, both feet touching, and arms hanging freely. The measuring tape
should be made of a material that is not easily stretched, such as fiberglass. The tape should be placed
perpendicular to the long axis of the body and horizontal to the floor and applied with sufficient tension to
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conform to the measurement surface. Although not normally performed in the office, waist
circumference measurements are typically taken three times and recorded to the nearest 0.1 cm in a
research setting. And although specific techniques have been recommended for measuring waist
circumference in the clinical setting, there is no uniformly accepted approach. However, it is essential
that both healthcare practitioners, technicians, and patients use appropriate techniques for measuring waist
circumference, so reliable data can be obtained.
Reference(s):
Klein S, Allison DB, Heymsfield SB, et al; Association for Weight Management and Obesity Prevention;
NAASO; Obesity Society; American Society for Nutrition; American Diabetes Association. Waist
circumference and CMR: a consensus statement from Shaping America's Health: Association for
Weight Management and Obesity Prevention; NAASO, the Obesity Society; the American Society for
Nutrition; and the American Diabetes Association. Diabetes Care. 2007;30:1647-1652.
10. HT has a waist circumference of 38 inches. For a male, this measurement is less than the
guidelines cite as having an increased CMR due to abdominal obesity. What would be a more
accurate measure to determine an increased risk from abdominal obesity?
A. BMI
B. Waist-to-hip ratio
C. Waist-to-height ratio (index of central obesity)
D. Total cholesterol/HDL-C ratio
E. None of the above
Answer: C
Rationale:
Along with BMI, waist circumference and WHR are also associated with increased CMR and risk of
death. However, the WHtR (also referred to as the Index of Central Obesity) has emerged as a promising
index for identification of subjects at increased CMR in both adults and children, as the calculation takes
into account height, which is important particularly in shorter individuals and those of various ethnicities.
A proposed single value of <0.5 is recommend as a cutoff for increased risk, whether male or female,
adult or child, irrespective of ethnicity. Several studies support this conclusion.
Kodama et al showed that WHtR had a stronger association with incident diabetes than BMI and WHR.
Ashwell et al showed that WHtR had a better discriminatory power than BMI and WC in detecting
several CMR factors. And in a meta-analysis by Savva et al, the overall ratio of relative risks clearly
indicated WHtR is superior to BMI in detecting type 2 diabetes. Regarding ethnicity, the association of
WHtR with type 2 diabetes was stronger in both Asians and non-Asians, whether male or female.
Because of this, it is recommended WHtR be included in the routine screening and assessment of
overweight and obese children, and those with an elevated WHtR should undergo a further CMR
assessment.
With a WHtR of 0.54, HT is at increased CMR, despite having a waist circumference less than that
defined by the guidelines as a measure of increased CMR.
Reference(s):
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Savva SC, Tornaritis M, Savva ME, et al. Waist circumference and waist-to-height ratio are better
predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat
Metab Disord. 2000;24:1453–1458.
Ashwell M, Hsieh SD. Six reasons why the waist-to-height ratio is a rapid and effective global indicator
for health risks of obesity and how its use could simplify the international public health message on
obesity. Int J Food Sci Nutr. 2005;56:303–307.
Parikh RM, Joshi SR, Pandia K. Index of central obesity is better than waist circumference in defining
metabolic syndrome. Metab. Syndr. Relat. Disord. 2009;7:525–527.
Schneider HJ, Friedrich N, Klotsche J, et al. The predictive value of different measures of obesity for
incident cardiovascular events and mortality. J Clin Endocrinol Metab. 2010;95:1777-1785.
Schneider HJ, Klotsche J, Silber S, Stalla GK, Wittchen HU. Measuring abdominal obesity: effects of
height on distribution of cardiometabolic risk factors risk using waist circumference and waist-to-height
ratio. Diabetes Care. 2011;34:e7.
Kodama S, Horikawa C, Fujihara K, et al. Comparisons of the strength of associations with future type 2
diabetes risk among anthropometric obesity indicators, including waist-to-height ratio: a meta-analysis.
Am J Epidemiol. 2012;176:959–969.
Browning LM, Hsieh SD, Ashwell M. A systematic review of waist-to-height ratio as a screening tool for
the prediction of cardiovascular disease and diabetes: 0.5 could be a suitable global boundary value.
Nutr Res Rev. 2010;23:247–269.
Ashwell M, Gunn P, Gibson S. Waist-to-height ratio is a better screening tool than waist circumference
and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev.
2012;13:275-286.
Khoury M, Manlhiot C, McCrindle BW. Role of the waist/height ratio in the cardiometabolic risk
assessment of children classified by body mass index. J Am Coll Cardiol. 2013;62:742-751.
American Diabetes Association. Standards of Medical Care in Diabetes—2014. Diabetes Care.
2014;37:S81-S90.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
11. Based upon clinical evidence, each of the following race/ethnicities may require a lower cutoff
level for waist circumference EXCEPT:
A. African American
B. Japanese
C. Caucasian
D. South Asians
E. Hispanic Americans
Answer: C
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Rationale:
In various guidelines and the Association’s Standards of Care, cutoff values for waist circumference (>40
inches for men; ≥35 inches for women) were derived from values that correlated with a BMI ≥30 kg/m2.
The International Diabetes Federation recommends ethnic-specific values for determining cutoffs for
waist circumference of different ethnicities, such as South Asians, Japanese, and Chinese. Accordingly,
certain races/ethnicities in the U.S. may require a lower cutoff, including African Americans, Hispanic
Americans, South Asians, Chinese, and Japanese because of a greater risk for developing CMR.
Reference(s):
National Institutes of Health, National Heart, Lung, and Blood Institute: Clinical guidelines on the
identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. Obes
Res. 1998;6(Suppl. 2): 51S–209S.
Okosun IS, Liao Y, Rotimi CN, Prewitt TE, Cooper RS. Abdominal adiposity and clustering of multiple
metabolic syndrome in white, black and Hispanic Americans. Ann Epidemiol. 2000;10:263-270.
Carnethon MR, Loria CM, Hill JO, Sidney S, Savage PJ, Liu K. Risk factors for the metabolic syndrome:
the Coronary Artery Risk Development in Young Adults (CARDIA) Study, 1985-2001. Diabetes Care.
2004;27:2707-2715.
Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic
syndrome--a new worldwide definition. Lancet. 2005;366:1059-1062.
Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an
American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement.
Circulation. 2005;112:2735-2752.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
Case 1 Continuation
12. You discuss with HT some treatment options, including increasing his physical activity,
intensity of exercise, weight management, and diet. In a person with prediabetes, weight
management and routine exercise:
A. Are seldom advised for patients with clear CMR
B. Can delay or prevent the onset of diabetes
C. Improve risk factors for CV disease
D. Both b and c
E. All of the above
Answer: D
Rationale:
Persons with prediabetes, including those with regular access to health care, might benefit from
educational efforts aimed at increasing awareness that they are at risk for developing type 2 diabetes, as
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they can reduce that risk by making modest lifestyle changes. Evidence-based lifestyle programs that
encouraged dietary changes, moderate-intensity physical activity, and modest weight loss for persons diet
with prediabetes have shown a delay or prevention of type 2 diabetes. Exploratory analysis from the
Look AHEAD study results showed ILI was associated with a greater likelihood of partial remission of
type 2 diabetes compared with DSE. In the DPP, the incidence of type 2 diabetes in persons at high risk
was reduced by 58% in the lifestyle intervention group and 31% in the metformin group, as compared
with placebo; the lifestyle intervention was significantly more effective than metformin.
Reference(s):
Knowler WC, Barrett-Conner E, Fowler SE, et al; Diabetes Prevention Program Research Group.
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med.
2002;346:393–403.
Gregg EW, Chen H, Wagenknecht LE; Look AHEAD Research Group. Association of an intensive
lifestyle intervention with remission of type 2 diabetes. JAMA. 2012;308:2489-2496.
13. The American Diabetes Association recommends a structured program that emphasizes lifestyle
changes for individuals at high risk for developing type 2 diabetes. This type of program includes
which of the following:
A. Regular physical activity of less than 90 minutes per week.
B. Moderate physical activity of at least 150 minutes per week.
C. Dietary strategies that include only a reduction in calories to achieve a targeted body weight loss of
3%.
D. Dietary strategies that include both a reduction in calories and reduced intake of dietary fat to achieve
a targeted body weight loss of 7%.
E. B and D above
Answer: E
Rationale:
Evidence-based lifestyle programs that encouraged dietary changes, moderate-intensity physical activity,
and modest weight loss for persons with prediabetes have shown a delay or prevention in the onset of type
2 diabetes. The Association recommends structured programs that emphasize lifestyle changes for
individuals at high risk for developing type 2 diabetes. These programs should include moderate physical
activity of 150 min per week or intense physical activity of 90 minutes per week, and dietary strategies
(reduced calories and reduced intake of dietary fat) in order to achieve a targeted body weight loss of 7%.
Reference(s):
Knowler WC, Barrett-Conner E, Fowler SE, et al; Diabetes Prevention Program Research Group.
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med.
2002;346:393–403.
Gregg EW, Chen H, Wagenknecht LE; Look AHEAD Research Group. Association of an intensive
lifestyle intervention with remission of type 2 diabetes. JAMA. 2012;308:2489-2496.
Page 15 of 69
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Case 1 Continuation
It is important that HT is exercising, but he is only maintaining his weight, not losing nor gaining.
And his latest A1c is 6.3%. He asks what more can be done to reverse his prediabetes and prevent
type 2 diabetes.
14. As noted, exercise and weight reduction are important for preventing type 2 diabetes. What
percent of individuals with prediabetes who do not lose weight and/or do not engage in moderate
physical activity will progress to type 2 diabetes during the average 3 years of follow-up?
A. 1%
B. 4%
C. 11%
D. 17%
E. 21%
Answer: C
Rationale:
There is a relatively high risk for the future development of diabetes for individuals with IFG, IGT, and/or
elevated A1c despite not having diabetes by a clinical definition, a condition called prediabetes. In 2010,
approximately one in three U.S. adults aged ≥20 years (an estimated 79 million persons) had prediabetes.
Of these, only 11% of persons with prediabetes were aware that they had the condition. And each year
approximately 11% of persons with prediabetes who do not lose weight and/or do not engage in moderate
physical activity will progress to type 2 diabetes.
Reference(s):
CDC. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes
in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, CDC; 2011.
Available at http://www.cdc.gov/diabetes/pubs/factsheet11.htm. Accessed October 9, 2013.
Geiss LS, James C, Gregg EW, et al. Diabetes risk reduction behaviors among U.S. adults with
prediabetes. Am J Prev Med. 2010;38:403–409.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care.
2014;37 Suppl 1:S81 - 90.
Centers for Disease Control and Prevention (CDC). Awareness of prediabetes - United States, 2005-2010.
MMWR Morb Mortal Wkly Rep. 2013;62:209-212.
15. In addition to exercise as a cornerstone therapy for diabetes prevention, the Association’s
Standards of Care recommends healthcare practitioners consider which of the following for
individuals with IFG, IGT, and an A1c of 5.7–6.4%?
A. Sulfonylurea
B. DPP-4 antagonist
C. Metformin
Page 16 of 69
D. GLP-1 receptor agonist
E. Alpha-glucosidase inhibitor
Answer: C
Rationale:
Metformin has been shown to activate the key regulatory enzymes that may prevent the transition from
prediabetes to type 2 diabetes. In one study, insulin sensitivity was considerably higher after 12 weeks of
exercise training and/or metformin for individuals with prediabetes. Other evidence showed a greater
weight loss (2-5 kg) occurred with the addition of metformin compared with lifestyle modification alone.
The DPP also demonstrated that either lifestyle modification (i.e., low-fat diet and increased physical
activity) or metformin can reduce the transition from prediabetes to type 2 diabetes.
In addition to exercise as a cornerstone therapy for diabetes prevention, the Association’s Standards of
Care also recommends healthcare practitioners consider metformin therapy for individuals with IGT, IFG,
or an A1c of 5.7–6.4%, especially for those with BMI ≥35 kg/m2, aged 60 years or older, and women with
prior GDM.
Reference(s):
Malin SK, Gerber R, Chipkin SR, Braun B. Independent and combined effects of exercise training and
metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012;35:131-136.
Atabek ME, Pirgon O. Use of metformin in obese adolescents with hyperinsulinemia: a 6-month,
randomized, double-blind, placebo-controlled clinical trial. J Pediatr Endocrinol Metab. 2008;21:339–
348.
Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in
adolescents with insulin resistance. J Pediatr. 2008;152:817–822.
The Diabetes Prevention Program Research Group. Role of insulin secretion and sensitivity in the
evolution of type 2 diabetes in the diabetes prevention program: effects of lifestyle intervention and
metformin. Diabetes. 2005;54:2404–2414.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Page 17 of 69
Case Study #2
FD, a 68-year-old African American male, comes in for a routine clinic visit. He was diagnosed with
essential hypertension 8 years ago with a SBP, 146 mmHg; DBP, 98 mmHg; currently, his BP is
controlled on medication.
Social history: 40-year history as a 1 pack-per-day smoker; no family history of premature coronary
disease. Was a business executive in the pharmaceutical industry; he is currently employed as a
consultant in healthcare. Physical activity is limited to 20 minutes per day of walking to and from work.
Diet is erratic, frequently dining out with clients, including 2-3 glasses of wine a day.
Physical examination: SBP/DPB, 138/87 mmHg (average of 3 readings); body mass index (BMI), 31
kg/m2; waist circumference, 42 inches (102.9 cm).
Recent lab data: fasting lipid panel is notable for total cholesterol, 218 mg/dL; LDL-C, 144 mg/dL; HDL-
C, 29 mg/dL; triglycerides, 226 mg/dL; FPG, 115 mg/dL.
Medications: amlodipine 5 mg once daily.
Assessment: FD is an obese African American with essential hypertension, dyslipidemia, and several
factors contributing to CMR.
Questions 16-35
16. Which of the following are modifiable CMR factors?
A. Race/ethnicity
B. Family history
C. Hypertension
D. Age
E. Gender
Answer: C
Rationale:
CV disease is the leading cause of death in the U.S. and many parts of the world. Modifiable CV and
CMR factors include obesity, tobacco use, physical inactivity, unhealthy diet, hypertension, abnormal
lipid metabolism (e.g. elevated LDL-C), as well as a cluster of interrelated metabolic risk factors, such as
inflammation/hypercoagulation and insulin resistance.
FD has a total of 7 modifiable CMR factors. Of those listed above, he has hypertension; family history,
racial/ethnicity, gender, and age are non-modifiable. His other modifiable CMR factors include
physically inactive (walks only 20 minutes per day), being overweight, has dyslipidemia, smokes, eats an
unhealthy diet, and is insulin resistant. He probably has some level of vascular inflammation based upon
his an elevated triglyceride/HDL-C ratio (indicating insulin resistance), but a CRP level would help to
determine the presence of that risk factor.
Reference(s):
Grundy SM. Primary prevention of coronary heart disease: integrating risk assessment with intervention.
Circulation. 1999;100:988-998.
Page 18 of 69
Cannon CP. Cardiovascular disease and modifiable cardiometabolic risk factors. Clin Cornerstone.
2008;9:24-38.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
17. Each of the following statements is correct regarding CMR in different ethnicities EXCEPT:
A. CV disease, diabetes and related risk factors occur at higher rates among certain racial and ethnic
groups, including African Americans and Hispanic Americans.
B. African American men and women have the highest age-adjusted prevalence of high blood pressure.
C. African American women have the highest age-adjusted prevalence of abdominal obesity.
D. Conventional risk criteria does not need to be adjusted to accommodate for differences across ethnic
groups and, in turn, gain a more accurate assessment of CMR and existing disease.
E. Death rates from heart disease are higher among adults that are African American than Caucasians.
Answer: D
Rationale:
The prevalence, impact, and control of diabetes and CV disease differ across racial and ethnic subgroups
of the U.S. population. For example, in African Americans, hypertension is more common, more severe,
and develops at an earlier age. This group also has a greater prevalence of other risk factors, especially
obesity. However, much of the disparity among ethnic groups may be attributable to differences in
socioeconomic condition, access to health care, or attitudes toward health-related information.
Demographic factors also influence the likelihood of other risk factors for type 2 diabetes and CV disease.
Overweight and obesity correlate with a higher incidence of type 2 diabetes, hypertension, and heart
disease. Hispanics, Native Americans, and African Americans are all more likely than Caucasians to be
overweight or obese, even as children, so their overall risk as demographic groups for developing diabetes
and/or CV disease is greater than that of the Caucasian population.
Reference(s):
Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High
Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7
report. JAMA. 2003;289:2560–2572.
Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults,
1999–2000. JAMA. 2002; 288:1723–1727.
Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from
the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–372.
Park Y-W, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome:
prevalence and associated risk factor findings in the US population from the Third National Health and
Nutrition Examination Survey, 1988–1994. Arch Intern Med. 2003;163:427–436.
Page 19 of 69
18. Which of the following statements is CORRECT regarding CMR?
A. Only pharmacologic interventions have been proven to benefit patients with CMR.
B. Treatment goals for patients with CMR include achieving targets for blood glucose, blood pressure,
and dyslipidemia.
C. All patients with elevated high-density lipoprotein cholesterol need to be treated aggressively with
lifestyle modifications and adjunctive drug therapies.
D. Research results are inconclusive in the need for primary prevention of obesity beginning in
childhood.
E. The risk of myocardial infarction, strokes, and CV death is not increased.
Answer: B
Rationale:
The primary treatment of elevated CMR is lifestyle modification, as it has been shown to provide benefit
in patients with CMR. In addition to glycemic control, both national and international guidelines on
management of diabetes emphasize control of blood pressure, dyslipidemia, and obesity. The
INTERHEART study revealed nine easily measurable and modifiable risk factors (abnormal lipids;
smoking; hypertension; diabetes; abdominal obesity; psychosocial factors; decreased consumption of
fruits, vegetables, and alcohol; decreased physical activity) account for most of the risk for myocardial
infarction in all regions of the world, irrespective of gender and age. For individuals with CMR, the risk
of myocardial infarction, strokes, and CV death is 13 times higher than for those without CMR.
Reference(s):
UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 16: Overview of 6 years’ therapy
of type II diabetes: a progressive disease. Diabetes. 1995;44:1249-1258.
Yusuf S, Hawken S, Ounpuu S, et al, for the INTERHEART Study Investigators. Effect of potentially
modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study):
case control study. Lancet. 2004;364:937-952.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
19. Which factor(s) play(s) a clear role in increasing a person’s CMR, but are not included in the
traditional classification of metabolic syndrome?
A. HDL-C levels
B. Tobacco use
C. Hypertension
D. Waist circumference
E. All of the above
Answer: B
Rationale:
There are many individuals who have a constellation of major risk factors, life-habit risk factors, and
emerging risk factors that constitute a condition called the metabolic syndrome. Factors characteristic of
Page 20 of 69
this syndrome include abdominal obesity, atherogenic dyslipidemia (elevated triglyceride, small LDL
particles, low HDL cholesterol, raised SBP/DBP, insulin resistance (with or without glucose intolerance),
and prothrombotic and proinflammatory states.
The term metabolic syndrome serves a useful purpose in that it emphasizes risk factor clustering and the
importance of insulin resistance. However, it does not include other factors known to be strongly
correlated with CV risk. CMR encompasses those risk factors that predispose an individual for diabetes
and CV disease. It includes those factors in the definition of metabolic syndrome, as well as age, tobacco
use, and LDL-C.
Reference(s):
Eckel RH, Kahn R, Robertson RM, Rizza RA. Preventing cardiovascular disease and diabetes: a call to
action from the American Diabetes Association and the American Heart Association. Circulation
2006;113:2943-2946.
Leiter LA, Fitchett DH, Gilbert RE, Gupta M, Mancini GB, McFarlane PA, et al. Cardiometabolic risk in
Canada: a detailed analysis and position paper by the cardiometabolic risk working group. Can J
Cardiol. 2011;27(2):e1–33.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce
cardiovascular risk: a report of the American College of Cardiology American/Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
20. The Association’s Standards of Care endorse the preferred use of which of the following as a
treatment target when triglycerides levels are >200 mg/dL because of ease of calculation and does
not rely on any statistical estimates?
A. LDL-C levels
B. HDL-C levels
C. Non-HDL-C levels
D. Triglyceride/VLDL cholesterol ratio
E. LDL-C/HDL-C ratio
Answer: C
Rationale:
Unlike LDL-C, non-HDL-C represents the cholesterol content that is present in all the atherogenic
lipoproteins. Non-HDL-C was added in ATP-III as a secondary treatment target in patients with elevated
triglycerides (>200 mg/dL), with a treatment target being 30 mg/dL above the LDL-C treatment target.
The addition of non-HDL-C as a treatment target reflects the recognition of this calculated value as a
predictive factor in CV disease. The Association’s Standards of Care still endorses this parameter.
The more recent ACC/AHA Guidelines on the management of cholesterol, however, makes no
recommendation either for or against specific non-HDL–C goals for the primary or secondary prevention
of arteriosclerotic CV disease.
Page 21 of 69
Reference(s):
Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol in Adults (Adult Treatment
Panel III) Executive Summary of The Third Report of The National Cholesterol Education Program
(NCEP). JAMA. 2001:2486–2497.
Lu W, Resnick HE, Jablonski KA, et al. Non-HDL cholesterol as a predictor of cardiovascular disease in
type 2 diabetes: the Strong Heart Study. Diabetes Care. 2003;26:16-23.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of
cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood
cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of
Cardiology/American Heart Association. Circulation 2013; available at: http://circ.ahajournals.org.
21. What formula is used to calculate non-HDL-C?
A. LDL-C level minus HDL-C level
B. Triglyceride level minus LDL-C level
C. Total cholesterol level minus HDL-C level
D. Total cholesterol level minus LDL-C level
E. Triglyceride level divided by 3 plus LDL-C level
Answer: C
Rationale:
Non-HDL-C is calculated as subtracting the HDL cholesterol level from the total cholesterol level (TC
minus HDL cholesterol). It can also be calculated by dividing the triglyceride level by 5 and add that
value to the LDL cholesterol level. The reference ranges for non-HDL-C are based on National
Cholesterol Education III guidelines:
* Desirable: <130 mg/dL
* Borderline high: 139-159 mg/dL
* High: 160-189 mg/dL
* Very high: ≥190 mg/dL
Reference(s):
Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol In Adults (Adult Treatment
Panel III) Executive Summary of The Third Report of The National Cholesterol Education Program
(NCEP). JAMA. 2001:2486–2497.
Lu W, Resnick HE, Jablonski KA, et al. Non-HDL cholesterol as a predictor of cardiovascular disease in
type 2 diabetes: the Strong Heart Study. Diabetes Care. 2003;26:16-23.
Page 22 of 69
22. The more inclusive paradigm of CMR recognizes that:
A. Every risk factor should be weighted equally
B. The whole is not greater than the sum of its parts; that is, each risk factor has differential effects on
future CV disease risk
C. Most markers have similar predictive importance for CV disease across all patients
D. None of the above
E. All of the above
Answer: B
Rationale:
CMR is continuous. That is, individuals have varying levels of CMR depending on the number and
severity of their risk factors. When assessing a patient for comprehensive risk, a thorough documentation
of the patient’s history should be done, including documentation of age, ethnicity, smoking status,
physical activity level, diet, family history of premature CV disease risk or type 2 diabetes, and
comorbidities. In addition, physical examination should include measurement of waist circumference and
blood pressure (average of 3 readings), and calculation of body mass index. Lab results should include a
fasting lipid panel, FPG, and creatinine or estimated glomerular filtration rate. A majority of these
encompass CMR.
Evaluating patients for all contributory risk factors means there is more likelihood of identifying patients
at high risk for CV disease or diabetes, allowing clinicians to intervene sooner with education and
treatment. However, CMR recognizes that not all risk factors can be weighted equally, given their
differential effects on future risk of CV disease or diabetes.
Reference(s):
Vasudevan AR, Ballantyne CM. Cardiometabolic risk assessment: an approach to the prevention of
cardiovascular disease and diabetes mellitus. Clin Cornerstone. 2005;7:7-16.
Dzau VJ, Antman EM, Black HR, et al. The cardiovascular disease continuum validated: clinical
evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors
through stable coronary artery disease). Circulation. 2006;114:2850-2870.
23. Which of the following are major risk factors for developing type 2 diabetes?
A. Overweight/obesity
B. Increase in insulin sensitivity
C. Increased physical activity
D. Elevated HDL-C level
E. All of the above
Answer: A
Rationale:
Recognizing clinical signs and identifying risk factors in individuals at risk for developing diabetes are
essential for preventing the onset of the disease. These signs/risk factors include insulin resistance, a lack
of physical activity, and reduced HDL-C level. Having a BMI >25 kg/m2 is defined as being overweight;
Page 23 of 69
a BMI >30 kg/m2 is defined as being obese. An elevated BMI is a risk factor for developing type 2
diabetes and should be assessed along with other risk factors to determine an individual’s level of CMR.
Reference(s):
Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease.
Nature. 2006;444:875–880.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
24. According to the Association’s Standards of Care, which of the following lipid parameters is a
more accurate predictor of CV risk than serum total cholesterol levels, and thus is often the initial
target for treatment?
A. HDL-C
B. LDL-C
C. Triglycerides
D. VLDL-C
E. All of the above
Answer: B
Rationale:
Lipoprotein measurements are used to better assess CMR and prescribe tailored therapies to control blood
lipids to reduce the risk of disease and related complications. Of these, LDL-C has traditionally been
considered a more accurate predictor of CV risk than serum total-C level and is often the initial target for
therapy, according to the Association’s Standards of Care. High levels of LDL-C can lead to and advance
atherosclerosis.
However, the recent ACC/AHA Guidelines on Assessing CV risk employ a formula of various
parameters, including gender, age, racial background (either Caucasian or African American, but not
other ethnicities), SBP and blood pressure treatment, a ratio of total cholesterol to HDL-C, and the
presence or absence of diabetes and tobacco use. The guideline committee did not employ LDL-C as a
component of the risk calculator, nor does it make any recommendations either for or against specific
LDL–C goals for the primary or secondary prevention of atherosclerotic CV disease.
Reference(s):
Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol in Adults (Adult Treatment
Panel III) Executive Summary of the Third Report of The National Cholesterol Education Program
(NCEP). JAMA. 2001:2486–2497.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of
cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
Page 24 of 69
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood
cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of
Cardiology/American Heart Association. Circulation 2013; available at: http://circ.ahajournals.org.
Case 2 Continuation
25. You discuss with FD the risk of being overweight. What does research data reveal about
survival in individuals with a BMI of 30-35 kg/m2?
A. Life expectancy is decreased by 1-2 years
B. Life expectancy is decreased by 2-4 years
C. Life expectancy is decreased by 8-10 years
D. Life expectancy is not changed compared to patients with BMI of 25 kg/m2
E. Hazard is equivalent to smoking
Answer: B
Rationale:
In a collaborative analyses of baseline BMI versus mortality from 57 prospective studies, results revealed
that median survival is decreased by 0–1 year for people who would, by about age 60 years, reach a BMI
of 25–27·5 kg/m2, decreased by 1–2 years for those who would reach 27·5–30 kg/m2, and decreased by
2–4 years for those who would become obese (30–35 kg/m2). There was less information available for
those with a BMI >35 kg/m2, although median survival appears to be decreased by approximately 8–10
years in those who would become morbidly obese, that is a BMI of 40–50 kg/m2.
Reference(s):
Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000
adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-1096.
26. How does a body mass index (BMI) increase of 5 kg/m2 impact SBP and DBP?
A. SBP is increased but DBP is decreased
B. Neither SBP nor DBP are affected
C. SBP is decreased but DBP is increased
D. Both SBP and DBP are increased
E. SBP and DBP are increased in males but not in females
Answer: D
Rationale:
In collaborative analyses of baseline BMI versus mortality from 57 prospective studies, results revealed
that BMI (15–50 kg/m2) was associated positively (and nearly linearly) with both SBP and DBP. Results
showed that on average across all ages (15–89 years), every increase in BMI of 5 kg/m2 was associated
with at least 5 mm Hg increase in SBP and approximately a 4 mmHg increase in DBP in both males and
females.
Reference(s):
Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000
adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373:1083-1096.
Page 25 of 69
27. At the start of FD’s appointment, you take his BP. He comments that you do it differently than
others who have taken his BP. Which of the following is CORRECT according to guidelines for the
measurement of BP?
A. Measured while the patient is standing
B. Feet dangling from the exam table without supporting the arm
C. Immediately upon entering the exam room
D. Cuff size should be appropriate for the upper arm circumference
E. Elevated values should be confirmed later in the day
Answer: D
Rationale:
Measurement of blood pressure in the office should be done by a trained individual and follow the
guidelines established for persons who do not have diabetes. These guidelines include taking
measurements while patient is in a seated position and taken after 5 min of rest, feet are on the floor, and
the cuffed arm is being supported at heart level. The cuff size should be appropriate for the upper arm
circumference. If any blood pressures are elevated, those values should be confirmed on a separate day.
Reference(s):
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
28. Which of the following statements is TRUE regarding the age-specific relevance of blood
pressure to vascular mortality in the general population?
A. A higher risk for CV events and mortality begins at a SBP/DBP of >115/75 mmHg and doubles for
every 20-mmHg SBP or 10-mmHg DBP increase.
B. A lower risk for CV events and mortality begins at a SPB/DBP of >115/75 mmHg and declines for
every 20-mmHg SBP or 10-mmHg DBP decrease.
C. A lower risk for CV events and mortality begins at a SBP/DBP of >120/80 mmHg and doubles for
every 20-mmHg SBP or 10-mmHg DBP increase.
D. A higher risk for CV events and mortality begins at a SBP/DBP of >135/85 mmHg and triples for
every 10-mmHg SBP or 5-mmHg DBP increase.
E. There is no increase in the risk of CV events and mortality related to increases in blood pressure.
Answer: A
Rationale:
Although much of the focus on CV disease risk has been on frank hypertension, it is clear that risks for
CV disease increase at higher BP levels, even within the so-called normal range. An epidemiologic
pooling study of nearly 1 million men and women revealed that risk of mortality from CV disease
increases in a continuous fashion at SBP levels starting as low as 115 mmHg and DBP as low as 75
mmHg.
Within each decade of age at death, the proportional difference in the risk of vascular death associated
with a given absolute difference in usual blood pressure is about the same down to at least 115 mmHg
Page 26 of 69
usual SBP and 75 mm Hg usual DBP, below which there is little evidence. At ages 40-69 years, each
difference of 20 mmHg usual SBP (or, approximately equivalently, 10 mmHg usual DBP is associated
with more than a twofold difference in the stroke death rate, and with twofold differences in the death
rates from ischemic heart disease and from other vascular causes.
Reference(s):
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific
relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million
adults in 61 prospective studies. Lancet. 2002;360:1903–1913.
29. The ACCORD trial examined whether blood pressure lowering to SBP <120 mmHg provides
greater CV protection than a SBP level of 130–140 mmHg in patients with type 2 diabetes at high
risk for CV disease. Which of the following prespecified endpoint(s) was significantly reduced by
intensive blood pressure treatment?
A. All-cause mortality
B. Stroke and non-fatal stroke
C. CV mortality
D. Non-fatal myocardial infarction
E. All of the above
Answer: B
Rationale:
In ACCORD, blood pressure (BP) achieved in the intensive group was 119/64 mmHg and in the standard
group 133/70 mmHg; the goals were attained with an average of 3.4 hypertensive medications per
participant in the intensive group and 2.1 in the standard therapy group. The hazard ratio for the primary
end point (nonfatal MI, nonfatal stroke, and CV death) in the intensive group was 0.88 (p = .20). Of the
prespecified secondary end points, only stroke (p = .01) and nonfatal stroke (p = .03) were statistically
significantly reduced by intensive BP treatment.
Reference(s):
Cushman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-
pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575–1585.
30. With lifestyle modification, diet is a key component of managing a hypertensive patient with
several CMR factors. Which diet would you recommend for FD to adopt to reduce his blood
pressure?
A. A DASH eating plan
B. A Mediterranean diet eating plan
C. A variation of DASH with 10% protein replacement
D. Any of the above
E. None of the above
Answer: D
Rationale:
Page 27 of 69
Non-pharmacological therapy is reasonable in individuals with diabetes who have mildly elevated blood
pressure (SBP >120 mmHg or DBP >80 mmHg). If the blood pressure is confirmed to be ≥140 mmHg
SBP and/or ≥80 mmHg DBP, pharmacological therapy should be initiated along with non-
pharmacological therapy.
The most common food in Mediterranean-style diets are a higher intake of in fruits (particularly fresh),
vegetables (emphasizing root and green varieties), whole grains (cereals, breads, rice, or pasta), and fatty
fish (rich in omega–3 fatty acids); lower in red meat (and emphasizing lean meats); substituted lower-fat
or fat-free dairy products for higher-fat dairy foods; and used oils (olive or canola), nuts (walnuts,
almonds, or hazelnuts) or margarines blended with rapeseed or flaxseed oils in lieu of butter and other
fats. When compared to individuals given minimal advice on dietary patterns, middle-aged or older
adults with type 2 diabetes or at least 3 CVD risk factors who were counseled on a Mediterranean low-fat
dietary pattern reduced BP by 6–7/2–3 mmHg. In an observational study of healthy younger adults,
adherence to a Mediterranean pattern was associated with lower SBP/DBP (2–3/1–2 mmHg).
The DASH dietary pattern is high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish,
and nuts, and rich in potassium, magnesium, and calcium, as well as protein and fiber. It is low in
saturated fat, total fat, and cholesterol, sweets, SSBs, and red meats. In one study of adults with a
SBP/DBP of 120–159/80–95 mmHg, whose body weight and sodium intake were kept stable, the DASH
dietary pattern, when compared to a typical American diet of the 1990s, lowered SBP/DBP by 5–6/3
mmHg. The effect was seen in women and men, African American and non-African American adults,
older and younger adults, and hypertensive and non-hypertensive adults.
In OmniHeart, variations of the DASH dietary pattern were compared to DASH. One dietary pattern
replaced 10% of total daily energy with protein rather than carbohydrate; the other pattern replaced the
same amount of carbohydrate with unsaturated fat. In adults with SBP/DBP of 120–159/80–95 mmHg,
modifying the DASH dietary pattern by replacing 10% of calories from carbohydrates with the same
amount of either protein or unsaturated fat (8% monounsaturated and 2% polyunsaturated) lowered SBP
by 1 mmHg compared to the DASH dietary pattern. Among adults with SBP/DBP 140–159/90–95
mmHg, these replacements lowered SBP by 3 mmHg relative to DASH.
The Association’s Standards of Care recommend lifestyle therapy for elevated blood pressure, which
consists of weight loss (if overweight); a DASH-style dietary pattern including reducing sodium and
increasing potassium intake; moderation of alcohol intake; and increased physical activity.
Reference(s):
Sacks FM, Svetkey LP, Vollmer WM, et al; DASH-Sodium Collaborative Research Group. Effects on
blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH)
diet. N Engl J Med. 2001;344:3–10.
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce
cardiovascular risk: a report of the American College of Cardiology American/Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Page 28 of 69
31. Which of the following statements is CORRECT regarding the daily requirement of sodium for
individuals with hypertension?
A. Consume up to 4,000 mg of sodium per day.
B. Reduce sodium intake to below 1,500 mg per day.
C. Consume no more than 2,400 mg of sodium per day.
D. There is no maximum daily amount of sodium.
E. None of the above.
Answer: B
Rationale:
Reduction of sodium intake can lower BP an additional 2-8 mmHg. The most recent ACC/AHA
guidelines recommend individuals with hypertension reduce their intake of sodium by at least 1,000 mg
per day since that will lower BP, even if the desired level of sodium intake is not achieved, which is no
more than 2,400 mg of sodium/day. If needed, further reduction of sodium intake to 1,500 mg per day is
desirable, since it is associated with even greater reduction in BP. The Association’s Standards of Care
recommend individuals with diabetes and hypertension reduce their sodium intake to below 1,500
mg/day.
Reference(s):
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce
cardiovascular risk: a report of the American College of Cardiology American/Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
32. FD is taking amlodipine, a non-dihydropyridine calcium channel blocker (CCB) for BP control.
For patients with CMR and elevated blood pressure, which class of drugs is recommended as the
first choice treatment?
A. ACE inhibitor or ARB
B. Alpha blocker
C. Beta blocker
D. Non-dihydropyridine CCB
E. Diuretic
Answer: A
Rationale:
Lowering of BP with regimens based on a variety of antihypertensive drugs, including ACE inhibitors,
ARBs, β-blockers, diuretics, and calcium channel blockers, has been shown to be effective in reducing
CV events. The Association’s Standards of Care recommend pharmacological therapy for patients with
diabetes and hypertension should be with a regimen that includes either an ACE inhibitor or an ARB. If
one class is not tolerated, the other should be substituted. This conclusion is substantiated by results from
a recent meta-analysis that showed ACE inhibitors may produce better outcomes in patients with diabetes
Page 29 of 69
than other antihypertensive medications. A meta-analysis of 63 randomized clinical trials reporting all-
cause mortality, dialysis requirement and serum creatinine levels in persons with diabetes who received
antihypertensive therapies evaluated treatments included ACE inhibitors, ARBs, alpha- and beta-blockers,
calcium-channel blockers and diuretics, alone or in combination. Results indicated ACE inhibitors
significantly decreased doubling of creatinine compared with placebo by 42%, whereas beta-blockers
significantly increased mortality risk.
Reference(s):
Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High
Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7
report. JAMA. 2003;289:2560–2572.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Wu HY, Huang JW, Lin HJ, et al. Comparative effectiveness of renin-angiotensin system blockers and
other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-
analysis. BMJ. 2013;347:f6008.
Go AS, Bauman M, Coleman King et al. An effective approach to high blood pressure control: a science
advisory from the American Heart Association, the American College of Cardiology, and the Centers
for Disease Control and Prevention. Hypertension. 2013 Nov 15. [Epub ahead of print]
33. If BP is not controlled on monotherapy, combination antihypertensive therapy is recommended.
In the action plan of your progress notes, which combination would you recommend if FD’s BP is
not controlled in the future?
A. ACE inhibitor or ARB plus dihydropyridine CCB
B. Switch to an ACE inhibitor or ARB plus thiazide diuretic
C. ARB plus thiazide diuretic
D. Beta blocker plus thiazide diuretic
E. Alpha blocker plus dihydropyridine CCB
Answer: B
Rationale:
The American Society of Hypertension/International Society of Hypertension and National Institute for
Health and Clinical Excellence guidelines recommend a RAAS inhibitor (ACE inhibitor or ARB) plus a
CCB, whereas the ACC/AHA guidelines on the science advisory from the ACC/AHA/CDC underline the
pivotal role of thiazide diuretics. The combination of a RAAS inhibitor with a CCB demonstrated the
best efficacy in reducing CV endpoint. In ACCOMPLISH, the combination of an ACE inhibitor and CCB
was shown to be beneficial in reducing the primary composite endpoint of CV events plus death from CV
causes versus an ACE inhibitor plus thiazide diuretic. However, a subgroup analysis revealed the
combination of an ACE inhibitor with a diuretic was more beneficial for those of African American origin
or individuals with systolic heart failure.
Page 30 of 69
Reference(s):
National Clinical Guideline Centre. Hypertension. Clinical management of primary hypertension in
adults. London (UK): National Institute for Health and Clinical Excellence (NICE); 2011 Aug. 36 p.
(Clinical guideline; no. 127). Available at: http://www.guideline.gov/content.aspx?id=34824. Accessed
November 17, 2013.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Wu HY, Huang JW, Lin HJ, et al. Comparative effectiveness of renin-angiotensin system blockers and
other antihypertensive drugs in patients with diabetes: systematic review and bayesian network meta-
analysis. BMJ. 2013;347:f6008.
Go AS, Bauman M, King SM, Fonarow GC, Lawrence W, Williams KA, Sanchez E. An Effective
Approach to High Blood Pressure Control: A Science Advisory from the American Heart Association,
the American College of Cardiology, and the Centers for Disease Control and Prevention. Hypertension.
2013 Nov 15. [Epub ahead of print].
Case 2 Continuation
34. Part of your discussion with FD involves smoking cessation and its impact on his long-term
treatment goals. With smoking cessation, what percent reduction in mortality could be expected
for an individual with CHD?
A. 10%
B. 23%
C. 36%
D. 41%
E. 63%
Answer: C
Rationale:
The results of the INTERHEART study showed smoking even one cigarette per day can increase the risk
of myocardial infarction (MI) by 5%. And results from a meta-analysis of the medical literature by
Critchley et al revealed a 36% reduction in crude relative risk (RR) of mortality for patients with coronary
heart disease (CHD) who quit compared with those who continued smoking. Thus, smoking cessation is
associated with a substantial reduction in risk of all-cause mortality among patients with CHD.
Reference(s):
Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with
coronary heart disease: a systematic review. JAMA. 2003;290:86-97.
Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk
factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control
study. Lancet. 2004;364:937–952.
Page 31 of 69
35. You want to test FD for type 2 diabetes. His FPG is 115 mg/dL. Each of the following would
help to differentiate whether or not FD has diabetes EXCEPT:
A. A1c ≥6.5% performed in a laboratory using a method that is NGSP certified and standardized to the
DCCT assay.
B. FPG (defined as no caloric intake for at least 8 hours) ≥126 mg/dL (7.0 mmol/L).
C. A 2-hour plasma glucose level during a 75-gram OGTT of 140 mg/dL (7.8 mmol/L) to 199 mg/dL
(11.0 mmol/L).
D. A 2-hour plasma glucose ≥200mg/dL (11.1mmol/L) during a 75-gram OGTT.
E. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma
glucose≥200 mg/dL (11.1 mmol/L).
Answer: C
Rationale:
This patient has an elevated FPG value between 100 and 125 mg/dL, also known as IFG, and the presence
of IFG is highly predictive of type 2 diabetes and should be confirmed by an OGTT. If the OGTT 2-hour
plasma glucose value is between 140 and 199 mg/dL, then the patient has IGT and prediabetes
encompasses both IFG and IGT. A plasma glucose value of ≥200 mg/dL after an OGTT confirms a
diagnosis of type 2 diabetes. An A1c measurement of >6.5% confirms the diagnosis of type 2 diabetes.
According to the Association’s Standards of Care, criteria for diagnosing diabetes are:
Criteria Comment
A1c >6.5%. The test should be performed in a laboratory using a
method that is NGSP certified and standardized to
the DCCT assay.*
OR
FPG >126 mg/dL (7.0 mmol/L) Fasting is defined as no caloric intake for at least 8
hours.*
OR
2-h plasma glucose >200mg/dL
(11.1mmol/L) during an OGTT
The test should be performed as described by the
WHO, using a glucose load containing the equivalent
of 75 g anhydrous glucose dissolved in water.*
OR
A random plasma glucose >200
mg/dL (11.1 mmol/L)
For persons with classic symptoms of hyperglycemia
or hyperglycemic crisis
* In the absence of unequivocal hyperglycemia, result should be confirmed by repeat
testing
Reference(s):
Page 32 of 69
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Case 2 Continuation
FD’s lab results come back and his FPG is 118 mg/dL and A1c is 6.2%. You assess that he does not have
type 2 diabetes and ask him to return in 6 months so you can reassess his adherence to your
recommendations of lifestyle modifications and management of his hypertension.
Page 33 of 69
Case Study #3
MR, a 37-year-old Hispanic male, comes in for an employment physical. He is currently employed as a
garage mechanic, but is applying for a position as manager of a parts department in an automobile
dealership. He states has been overweight since childhood, as were his parents, but cannot lose weight,
although he has tried many times. When trying to lose weight, he employed fad diets, some of which
were successful. Once he lost as much as 20 pounds, but eventually regained the weight and rebounded
past his baseline. MR does not exercise and leads a fairly sedentary life both at home and at work.
His family has recently begun to express concern about his risk of developing type 2 diabetes, and they
have convinced him to seek medical consultation. The patient states he has not seen a physician in 2
years because he has not adhered to either his hypertension or cholesterol-lowering therapy.
Past medical history: hypertension and hypercholesterolemia; no surgeries.
Family history: both mother and father are alive and both are diagnosed with hypertension and type 2
diabetes.
Physical Examination: height, 5’11” (180.3 cm); weight, 362 pounds (164.5 kg); body mass index (BMI),
46.2 kg/m2; waist circumference, 47 inches (119.3 cm); BP, 152/104 mmHg; heart rate, 82 bpm.
Laboratory results: total cholesterol 273 mg/dL; LDL-C 181 mg/dL; HDL-C, 37 mg/dL; triglycerides,
300 mg/dL; FPG, 113 mg/dL.
Social history: does not exercise; denies tobacco, illicit drug use; he drinks one or two beers a day after
work with his friends.
Medications: telmisartan 80 mg once daily; simvastatin 20 mg once daily (prescribed but non-adherent
with both).
Assessment: MR is a morbidly obese male, alert and oriented, in no acute distress. He is non-adherent to
antihypertensive and lipid-lowering therapies.
Questions 36-47
36. What is the most poorly controlled risk factor for individuals with type 2 diabetes?
A. A1c
B. Postprandial plasma glucose
C. Body weight
D. Waist circumference
E. FPG
Answer: C
Rationale:
With a population-based mean BMI remaining in the obese range (33 kg/m2) and waist circumference in
the range defining abdominal obesity, excess body weight remains the most poorly controlled risk factor
in those with type 2 diabetes. Study results show only 11% patients have a BMI <25 kg/m2 and 16%
meet the recommended waist circumference levels of ≤40 inches in males and ≤35 inches in females.
Page 34 of 69
This has implications for long-term control of A1c and therefore the development of diabetes-related
complications, including CVD, CKD, retinopathy and neuropathy
Reference(s):
Ross SA, Dzida G, Vora J, et al. Impact of weight gain on outcomes in type 2 diabetes. Curr Med Res
Opin. 2011;27:1431–1438.
Wong ND, Patao C, Wong K, Malik S, Franklin SS, Iloeje U. Trends in control of cardiovascular risk
factors among US adults with type 2 diabetes from 1999 to 2010: Comparison by prevalent
cardiovascular disease status. Diab Vasc Dis Res. 2013;10:505-513.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
37. When taking this patient’s history of weight gain and loss over time, questions that should be
asked include:
A. Family history of obesity
B. Dietary habits
C. Level of physical activity
D. Details of previous weight loss attempts
E. All of the above
Answer: E
Rationale:
To determine a direction for management of a person’s obesity, clinicians need to assess weight and
lifestyle histories to determine potential contributory factors as to why they are obese. This assessment
includes asking questions about history of weight gain and loss over time, details of previous weight loss
attempts, dietary habits, physical activity, family history of obesity, and other medical conditions or
medications that may affect weight. The answer can provide useful information about the origins of or
maintaining factors for overweight and obesity, including success and difficulties with previous weight
loss or maintenance efforts, as well as assist the clinician in determining any adjustments to the patient’s
medical regimen and weight management efforts.
Reference(s):
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
Page 35 of 69
38. For obese individuals with type 2 diabetes, most common perceived barriers to exercise include:
A. Lack of time and physical discomfort
B. Easily measure results
C. Can vary the goals depending on their desired outcome
D. Self-evaluation of progress
E. Goals can be re-evaluated and adjusted periodically to maintain the desired therapeutic effect
Answer: A
Rationale:
The promotion of physical activity requires some understanding of the principles of behavior change and
of habit development. Additionally, barriers to physical activity and correlates of success with long-term
exercise should be considered. Five components of behavior change and self-regulation include: the
setting of realistic and simple goals, self-monitoring of personal behaviors linked to goal attainment,
feedback about progress toward goals, self-evaluation of progress, and corrective behavior leading to
effective movement toward goals.
For obese individuals with type 2 diabetes, the most common perceived barriers to exercise were lack of
time and physical discomfort, although these barriers varied with age, gender and marital status.
Exercises that are most likely to be successful in the long term are moderate in intensity, relatively
inexpensive, simple, and convenient and include a social component. Parameters for a successful
exercise program include being patient-appropriate, considers co-morbidities, is measurable, in a form
that allows the HCP to address barriers and patient adherence, will vary depending on the desired
outcomes, and is reevaluated and adjusted periodically to maintain the desired therapeutic effect.
Reference(s):
Egan AM, Mahmood WA, Fenton R, et al. Barriers to exercise in obese patients with type 2 diabetes.
QJM. 2013 Mar 23. [Epub ahead of print].
Williams MV, Davis T, Parker RM, Weiss BD. The role of health literacy in patient-physician
communication. Fam Med. 2002;34:383-289.
Brawley LR, Rejeski WJ, King AC. Promoting physical activity for older adults: the challenges for
changing behavior. Am J Prev Med. 2003;25(3 suppl 2):172–183.
Fletcher GF, Ades PA, Kligfield P, et al; American Heart Association Exercise, Cardiac Rehabilitation,
and Prevention Committee of the Council on Clinical Cardiology, Council on Nutrition, Physical
Activity and Metabolism, Council on Cardiovascular and Stroke Nursing, and Council on Epidemiology
and Prevention. Exercise standards for testing and training: a scientific statement from the American
Heart Association. Circulation. 2013;128:873-934.
39. MR was able to lose weight but was not able to maintain that weight loss. Factors that
contribute to a person’s inability to retain maximal weight loss include:
A. Socioeconomic status
B. An unsupportive environment
Page 36 of 69
C. Compensatory changes in circulating hormones that encourage weight regain after weight loss is
achieved
D. A and B above
E. All of the above
Answer: E
Rationale:
Long-term maintenance of weight, following weight reduction, is possible; however, research suggests an
intensive program with long-term support is required. As a result, many individuals will regain a portion
of their initial weight loss. Factors contributing to the individual’s inability to retain maximal weight loss
include socioeconomic status, an unsupportive environment, and physiological changes, such as
compensatory changes in circulating hormones that encourage weight regain after weight loss is achieved.
Reference(s):
Franz MJ, VanWormer JJ, Crain AL, et al. Weight-loss outcomes: a systematic review and meta-analysis
of weight-loss clinical trials with a minimum 1-year follow-up. J Am Diet Assoc. 2007;107:1755–1767.
Warshaw HS. Nutrition therapy for adults with type 2 diabetes. In: American Diabetes Association Guide
to Nutrition Therapy for Diabetes. Franz MJ, Evert AB, Eds. Alexandria, VA, American Diabetes
Association, 2012, p. 117–142.
Look AHEAD Research Group. Cardiovascular effects of intensive lifestyle intervention in type 2
diabetes. N Engl J Med. 2013;369:145–154.
40. In the Look AHEAD study, weight loss strategies associated with lower BMI in overweight or
obese individuals with type 2 diabetes included:
A. Weekly self-weighing
B. Skipping breakfast
C. Increased intake of fast foods
D. Increasing physical activity
E. A and D above
Answer: E
Rationale:
In the Look AHEAD study, weight loss strategies associated with lower BMI in overweight or obese
individuals with type 2 diabetes included weekly self-weighing, regular consumption of breakfast, and
reduced intake of fast foods. Other successful strategies included increasing physical activity, reducing
portion sizes, using meal replacements (as appropriate), and encouraging individuals with diabetes to eat
those foods with the greatest consensus for improving health.
Reference(s):
Raynor HA, Jeffery RW, Ruggiero AM, et al; Look AHEAD (Action for Health in Diabetes) Research
Group. Weight loss strategies associated with BMI in overweight adults with type 2 diabetes at entry
into the Look AHEAD (Action for Health in Diabetes) trial. Diabetes Care. 2008;31:1299–1304.
Page 37 of 69
41. According to guidelines for the management of obesity, what is the initial goal recommended for
weight reduction?
A. 1% to 3%
B. 3% to 5%
C. 5% to 10%
D. 12% to 15%
E. >15%
Answer: C
Rationale:
Although 3% to 5% of body weight may lead to clinically meaningful reductions, in some risk factors for
CV disease, larger weight losses produce greater benefits. The latest ACC/AHA/TOS guidelines
recommend a 5% to 10% reduction of baseline body weight within 6 months as an initial goal. The
Association’s Standards of Care note at least a 7% of reduction in body weight is recommended.
Reference(s):
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
42. MR has a history of hypertension. Each of the following has been shown to be implicated in the
pathophysiology of obesity-related hypertension EXCEPT:
A. Increase in adiponectin
B. Increases in leptin levels
C. Renin-angiotensin-aldosterone system
D. Obstructive sleep apnea
E. Impairment in salt excretion
Answer: A
Rationale:
Obesity predisposes the kidney to reabsorb sodium by neural (SNS), hormonal (aldosterone and insulin),
and renovascular (angiotensin II) mechanisms. Leptin is produced in adipocytes and secreted into
plasma, where the circulating concentration reflects the fat mass of the individual. A potent appetite
suppressant, leptin, like insulin, stimulates the SNS. With regard to the RAAS, several mechanisms have
been thought to underlie its activation in obesity, including SNS stimulation of renin release and
angiotensinogen production in adipose tissue, especially intra-abdominal adipocytes.
Other factors that may be implicated in the pathophysiology of obesity-related hypertension include a
decrease in adiponectin, and obstructive sleep apnea, which stimulates the SNS. One study showed a
Page 38 of 69
significant negative correlation between plasma adiponectin concentration and mean, SBP, and DBP,
which suggests a decrease adiponectin level contributes to the clinical course of essential hypertension.
Obstructive sleep apnea, a well-recognized complication of obesity, is associated with increased SNS
activity; this activity persists during daytime wakefulness. Obesity-related hypertension can also be
caused by a decrease in natriuretic peptides, resulting in a consequent impairment in salt excretion.
Reference(s):
Adamczak M, Wiecek A, Funahashi T, et al. Decreased plasma adiponectin concentration in patients with
essential hypertension. Am J Hypertens. 2003;16:72–75.
Ahmed SB, Fisher ND, Stevanovic R, Hollenberg NK. Body mass index and angiotensin-dependent
control of the renal circulation in healthy humans. Hypertension. 2005;46:1316–1320.
Goodfriend TL. Obesity, sleep apnea, aldosterone, and hypertension. Curr Hypertens Rep. 2008;10:222–
226.
Sarzani R, Salvi F, Dessi-Fulgheri P, Rappelli A. Renin-angiotensin system, natriuretic peptides, obesity,
metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens. 2008;26:831–843.
43. Based upon his BMI category, MR is a candidate for which of the following interventions?
A. Diet and exercise
B. Diet, exercise, and behavioral counseling
C. Diet, exercise, and behavioral counseling; then pharmacotherapy
D. Diet, exercise, and behavioral counseling; then bariatric surgery
E. Diet, exercise, and behavioral counseling; pharmacotherapy; then bariatric surgery
Answer: E
Rationale:
Among overweight and obese adults, analyses of continuous BMI show that the greater the BMI, the
higher the risk of fatal CHD and combined fatal and nonfatal CHD in both men and women. With dietary
intervention in overweight and obese adults, average weight loss is maximal at 6 months with smaller
losses maintained for up to 2 years, while treatment and follow-up tapers. Weight loss achieved by
dietary techniques aimed at reducing daily energy intake ranges from 4 to 12 kg at 6-month follow-up.
Thereafter, slow weight regain is observed, with total weight loss at 1 year of 4 kg to 10 kg and at 2 years
of 3 kg to 4 kg.
The principal components of an effective high-intensity, on-site comprehensive-lifestyle intervention
includes prescription of a moderately-reduced calorie diet; a program of increased physical activity; and
the use of behavioral strategies to facilitate adherence to diet and activity recommendations. All 3
components should be included in the intervention.
If patients are unable to lose enough weight to meet weight or targeted health outcome goals with their
current treatment, consider offering or referring them for more intensive behavioral treatment than
currently being attempted, an alternate diet including options for meal replacement, referral to a nutrition
professional and the addition of obesity pharmacotherapy may be appropriate. The clinician should also
assess the patient’s medication regimen for drugs that may contribute to weight gain and consider
Page 39 of 69
adjustments if medically appropriate. If patients are unable to lose enough weight to meet weight or
targeted health outcome goals with their current treatment, consider offering or referring for more
intensive behavioral treatment than currently being attempted, and the patient may be referred for
evaluation for bariatric surgery.
According to the most recent clinical practice guidelines, those eligible for a bariatric surgical procedure
include individuals with a BMI >40 kg/m2 who have no coexisting medical problems and for which the
procedure would not be associated with excessive risks. In addition, individuals with a BMI >35 kg/m2
and 1 or more severe obesity-related co-morbidities, which include (but not inclusive of) type 2 diabetes,
hypertension, hyperlipidemia, OSA, OHS, or considerably impaired quality of life, may also be offered a
bariatric procedure.
Although those with BMI of 30–34.9 kg/m2 and with diabetes or at CMR may also be offered a bariatric
procedure, current evidence is limited by the number of subjects studied and lack of long-term data
demonstrating a net benefit. According to these guidelines, there is insufficient evidence for
recommending a bariatric surgical procedure independent of BMI criteria specifically for glycemic
control alone, lipid lowering alone, or CV disease risk reduction alone.
The following table outlines when weight-loss surgery is recommended after lifestyle modification and
pharmacotherapy.
Treatment Body Mass Index (Kg/m2)
25-26.9 27-29.9 30-34.9 35.0-39.9 >40
Diet, physical activity,
behavioral therapy Yes with comorbidities* Yes Yes Yes
Pharmacotherapy NO Yes with
comorbidities* Yes Yes Yes
Weight-loss surgery NO NO Yes Yes Yes
* Include but not limited to type 2 diabetes, hypertension, hyperlipidemia, OSA, OHS
According to the 2008 NIH guidelines, based upon his BMI, MR is a candidate for diet, exercise, and
pharmacotherapy for the management of his abdominal obesity, and a candidate for bariatric surgery if
these other interventions fail to accomplish his target weight goal.
Reference(s):
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
Mechanick JI, Youdim A, Jones DB, et al. Clinical practice guidelines for the perioperative nutritional,
metabolic, and nonsurgical support of the bariatric surgery patient-2013 update: co-sponsored by
Page 40 of 69
American Association of Clinical Endocrinologists, the Obesity Society, and American Society for
Metabolic & Bariatric Surgery. Endocr Pract. 2013;19:337-372.
National Institutes of Health, National Heart, Lung, and Blood Institute, North American Association for
the Study of Obesity. The Practical Guide: Identification, Evaluation and Treatment of Overweight and
Obesity in Adults. Rockville, MD: National Press Office; October 2000. NIH publication 00-4084.
Available at: http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf . Accessed November 13, 2013.
Case 3 Continuation
44. MR has implemented improved nutrition, physical activity, and behavior therapy. Which of the
following diets has been shown to improve CV risk factors, such as lipids, triglycerides, and blood
pressure in persons with diabetes?
A. Mediterranean
B. Vegetarian
C. Low fat
D. DASH
E. A and D above
Answer: E
Rationale:
Although mostly studied in the Mediterranean region, the Mediterranean-style eating pattern has been
observed to improve lipids, blood pressure, and triglycerides in persons with diabetes, as well as lowering
combined end points for CV disease events and stroke when supplemented with mixed nuts (including
walnuts, almonds, and hazelnuts) or olive oil. And for those following an energy-restricted
Mediterranean-style eating pattern, improvements in glycemic control were also achieved.
In a review of vegetarian and low-fat vegan studies in individuals with type 2 diabetes, diets ranging in
duration from 12 to 74 weeks did not consistently improve CV risk factors or glycemic control except
when energy intake was restricted and a loss of weight was measured.
There is limited evidence on the effects of the DASH eating plan on health outcomes specifically in
individuals with diabetes. One small study in individuals with type 2 diabetes revealed the DASH eating
plan, which included a sodium restriction of 2,300 mg/day, improved A1c, blood pressure, and other CV
risk factors. Despite this limited evidence, however, one would expect benefits of the DASH eating plan
in controlling blood pressure and lowering risk for CV disease that is seen for the general population
would also be beneficial for persons with diabetes.
Reference(s):
Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2
diabetes in adults. J Am Diet Assoc. 2010;110:1852–1889.
Esposito K, Maiorino MI, Ciotola M, et al. Effects of a Mediterranean-style diet on the need for
antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial.
Ann Intern Med. 2009;151:306–314.
Page 41 of 69
Elhayany A, Lustman A, Abel R, Attal-Singer J, Vinker S. A low carbohydrate Mediterranean diet
improves cardiovascular risk factors and diabetes control among overweight patients with type 2
diabetes mellitus: a 1-year prospective randomized intervention study. Diabetes Obes Metab.
2010;12:204–209.
Estruch R, Ros E, Salas-Salvadó J, et al; PREDIMED Study Investigators. Primary prevention of
cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279–1290.
Wheeler ML, Dunbar SA, Jaacks LM, et al. Macronutrients, food groups, and eating patterns in the
management of diabetes: a systematic review of the literature, 2010. Diabetes Care. 2012;35:434–445.
Sacks FM, Svetkey LP, Vollmer WM, et al., DASH-Sodium Collaborative Research Group. Effects on
blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH)
diet. N Engl J Med. 2001;344:3–10.
Azadbakht L, Fard NR, Karimi M, et al. Effects of the Dietary Approaches to Stop Hypertension (DASH)
eating plan on CV risks among type 2 diabetic patients: a randomized crossover clinical trial. Diabetes
Care. 2011;34:55–57.
Festa A, D’Agostino R Jr, Howard G, et al. Chronic subclinical inflammation as part of the insulin
resistance syndrome: the insulin resistance atherosclerosis study (IRAS). Circulation 2000;102:42–7.
45. From a nutritional perspective, intake of which of the following has a direct effect on
postprandial glucose levels in people with diabetes and is the primary macronutrient of concern in
glycemic management?
A. Fats
B. Carbohydrates
C. Protein
D. A and B above
E. All of the above
Answer: B
Rationale:
The primary micronutrient of concern in the glycemic management is carbohydrate. A meta-analysis
showed that at 6 months, low-carbohydrate diets were associated with greater improvements in
triglyceride and HDL-C concentrations than low-fat diets; however, LDL cholesterol was significantly
higher on the low-carbohydrate diets.
Reference(s):
Franz MJ, Powers MA, Leontos C, et al. The evidence for medical nutrition therapy for type 1 and type 2
diabetes in adults. J Am Diet Assoc. 2010;110:1852–1889.
46. Which of the following statements is CORRECT regarding the effectiveness of nutritional
therapy?
A. As an effective component of an overall treatment plan, nutrition therapy is recommended only for
individuals with type 2 diabetes.
Page 42 of 69
B. Individuals who have diabetes should receive individualized medical nutritional therapy (MNT) as
needed to achieve treatment goals, preferably provided by an RD familiar with the components of
diabetes MNT.
C. For individuals using fixed daily insulin doses, consistent carbohydrate intake with respect to time
and amount has no impact for improving glycemic control and/or reduce the risk for hypoglycemia.
D. Despite cost savings from diabetes nutrition therapy, evidence shows no improved outcomes such as
reduction in A1c.
E. Individuals with diabetes should receive DSME according to national standards and DSMS only
when the diagnosis of diabetes is made.
Answer: B
Rationale:
DSME and DSMS are critical elements of care for all individuals with either type 1 or type 2 diabetes,
and are necessary to improve outcomes in a disease that is largely self-managed. According to the latest
nutrition therapy recommendations, individuals who have diabetes should receive individualized MNT as
needed to achieve treatment goals, preferably provided by a registered dietician familiar with the
components of diabetes MNT. For those administering fixed daily doses of insulin, consistent
carbohydrate intake with respect to time and amount can result in improved glycemic control and reduce
the risk for hypoglycemia. Persons with diabetes should receive DSME according to national standards
and DSMS when their diabetes is diagnosed and as needed thereafter. In addition, diabetes nutrition
therapy can result in cost savings and improved outcomes such as reduction in A1c.
Reference(s):
Haas L, Maryniuk M, Beck J, et al. 2012 Standards Revision Task Force. National Standards for Diabetes
Self-Management Education and Support. Diabetes Care. 2012;35:2393–2401.
Evert AB, Boucher JL, Cypress M, et al. Nutrition therapy recommendations for the management of
adults with diabetes. Diabetes Care. 2013;36:3821-3842.
47. After instituting lifestyle modifications, MR still has a BMI of 39 kg/m2. Your treatment plan is
to next initiate pharmacotherapy if he had not achieved his target weight. Which of the following
drugs are NOT APPROVED for the long-term management of abdominal obesity?
A. Orlistat
B. Sibutramine
C. Lorcaserin
D. Phenteramine-topiarmate
E. C and D above
Answer: B
Rationale:
There are currently 3 FDA-approved drugs for the long-term management of abdominal obesity: orlistat,
lorcaserin, and phenteramine-topiarmate. Each are indicated as an adjunct to a reduced-calorie diet and
increased physical activity for chronic weight management in adult patients with an initial body mass
index (BMI) of:
Page 43 of 69
30 kg/m² or greater (obese), or
27 kg/m² or greater (overweight) in the presence of at least one weight related comorbid
condition, such as hypertension, dyslipidemia, type 2 diabetes.
If after 12 weeks on a maximal dose of the medication the patient has not lost at least 5% of initial body
weight, the provider should reassess the risk-to-benefit ratio of that medication for the patient, and
consider discontinuation of that drug.
Orlistat, a pancreatic lipase inhibitor that targets intestinal lipases, prevents the hydrolysis of triglycerides
and absorption of fatty acids and monoacylglycerols from the gut. In a multicenter 57-week study versus
placebo, orlistat demonstrated an 8.9% decrease in body weight (p < .05), an 0.18% decrease in A1c (p <
.05), and a significant decrease in FPG levels (p < .05).
Lorcaserin affects central serotonin subtype 2A receptors, resulting in decreased food intake and
increased satiety. It has been studied in obese patients with type 2 diabetes, producing approximately an
average weight loss of 5.5 kg over the course of 12 months.
The effect of phentermine on chronic weight management is likely mediated by release of catecholamines
in the hypothalamus, resulting in reduced appetite and decreased food consumption, but other metabolic
effects may also be involved; the exact mechanism of action is not known. The effects of topiramate may
be due to its effects on both appetite suppression and satiety enhancement, induced by a combination of
pharmacologic effects. The phentermine-controlled-release topiramate formulation has been shown to
decrease weight by an average of 12.2 kg over 52–104 weeks of treatment in various clinical studies.
Because of its effects on intestinal lipases, orlistat also causes socially unacceptable side effects, which
include oily spotting, increased flatus with discharge, and fecal urgency. Thus, fat-soluble vitamin levels
must be carefully monitored. Lorcaserin has been reported to increase the risk of psychiatric, cognitive,
and serotonergic adverse effects and phentermine–topiramate may increase the risk of metabolic acidosis,
glaucoma, and psychiatric and cognitive adverse effects.
FDA approval of phentermine–topiramate required a REMS, which includes a medication guide, a patient
brochure, and a formal training program for prescribers. This program informs both patients and
prescribers of the teratogenic risk and stress the need for women of reproductive potential to use effective
forms of contraception. REMS also permits only specially certified pharmacies to dispense phentermine–
topiramate.
Sibutramine is a central inhibitor of norepinephrine and serotonin reuptake and, to a lesser extent,
dopamine reuptake. Although shown to significantly decrease abdominal adiposity, lower triglyceride
and raise serum HDL-C levels, it was removed from the market due to unacceptable side effects,
specifically myocardial infarction and stroke.
Reference(s):
James WP, Astrup A, Finer N, et al, for the STORM Study Group. Effect of Sibutramine on weight
maintenance after weight loss: a randomised trial. Sibutramine Trial of Obesity Reduction and
Maintenance. Lancet. 2000;356:2119-2125.
Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database
Syst Rev. 2003:CD004094.
Page 44 of 69
Henness S, Perry CM. Orlistat: A review of its use in the management of obesity. Drugs. 2006;66:1625-
1656.
Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for
weight management. N Engl J Med. 2010;363:245–256.
Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese
adults: a randomized controlled trial. Obesity. 2011;20:330–342.
Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus
topiramate combination on weight and associated comorbidities in overweight and obese adults
(CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341–1352.
Colman E, Golden J, Roberts M, Egan A, Weaver J, Rosebraugh C. The FDA’s assessment of two drugs
for chronic weight management. N Engl J Med. 2012;367:1577–1579.
Taylor JR, Dietrich E, Powell J. Lorcaserin for weight management. Diabetes Metab Syndr Obes.
2013;6:209-216.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
Page 45 of 69
Case Study #4:
ERL, a 12-year-old Caucasian male, comes in for a school physical accompanied by his mother.
Physical exam: height, 5’5” (165 cm); weight, 195 lbs (88.6 kg); BMI, 32.5 kg/m2; waist circumference:
32” (81.3 cm); SPB: 132 mmHg; DBP: 80 mmHg (average of 3 readings); pulse: 84 beats per minute
(average of 3 readings).
Family history: Both parents are alive, but overweight due to lack of physical activity; both employed full
time as computer programmers; father has hypertension and diabetes; mother was told she has
prediabetes. Neither parent exercises nor are involved in any structured activity program.
Social history: ERL denies tobacco use, alcohol intake, or illicit drug use; has no structured exercise
program as his school discontinued gym classes; spends 3-4 hours a day playing video games; another
couple of hours a day on the computer doing his homework. He enjoys snack foods, especially potato
chips and drinking sugar sweetened beverages.
Lab results (within the past week): A1c, 6.4%; FPG, 105 mg/dL; total cholesterol, 240 mg/dL; LDL-C,
165 mg/dL; HDL-C, 31 mg/dL; triglycerides, 220 mg/dL.
Medications: None; all of his vaccinations are up-to-date.
You document ERL has several factors related to CMR and prescribe treatment with the goal of
preventing him from progressing to type 2 diabetes.
Questions 48-58
48. According the Association’s Standards of Care, each of the following meet the parameters for
CMR factors in this patient EXCEPT:
A. FPG ≥90 mg/dL.
B. Waist circumference >40 inches (102 cm) in males; >35 inches (88 cm) in females
C. BP ≥130/85 mmHg.
D. HDL-C level ≤40 mg/dL in males.
E. Triglyceride level ≥150 mg/dL.
Answer: A
Rationale:
A comprehensive risk assessment should include a thorough documentation of the patient’s history (age,
ethnicity, smoking status, physical activity level, diet, family history of premature CV disease or type 2
diabetes, and comorbidities), physical examination (BMI, waist circumference, and BP), and laboratory
test results (FPG, creatinine or estimated glomerular filtration rate, and fasting lipid profile). This
assessment should help guide the clinician to determine the level of CMR in any given patient. However,
this assessment should not be reserved strictly for adults, but starts at a much younger age.
According to the Association’s Standards of Care, parameters of CMR are highly concordant; in
aggregate they enhance risk for coronary heart disease at any given LDL-C level. Parameters for factors
in adults risk include:
FPG ≥110 mg/dL.
Page 46 of 69
Waist circumference >40 inches (102 cm) in males; >35 inches (88 cm) in females
Blood pressure ≥130/85 mmHg.
HDL-C level ≤40 mg/dL in males; ≤50 mg/dL in females.
Triglyceride level ≥150 mg/dL.
However, the diagnosis of CMR in children and adolescents requires the assessment of the waist
circumference (or BMI), SBP/DBP, lipids, and plasma glucose levels. Parameters for
children/adolescents were fixed for blood pressure, lipids and glucose; abdominal circumference points
and assessed by percentile although, the cut-offs for metabolic and blood pressure variables were not well
defined in children aged 6-10 years; therefore, only adiposity levels were evaluated (considering waist
circumference above the 90th percentile). The same criteria would be used for children aged 10-16 as in
adults: FPG ≥100 mg/dL, triglycerides ≥150 mg/dL, HDL-C <40 mg/dL or the use lipid lowering drugs
were considered risk factors as well SBP ≥130 or DBP ≥85 mmHg.
In a study of individuals ranging in age from 2 to 39 years who died from various causes (principally
trauma), antemortem data revealed the presence of CV risk factors, including increased BMI, SBP and
DPB, and serum concentrations of total cholesterol, triglycerides, LDL-C, and HDL-C. As a group, these
risk factors were significantly associated with the extent of lesion formation in the aorta and coronary
arteries (p < .001). The mean percentage of the intimal surface covered by lesions in patients with
different numbers of risk factors (0, 1, 2, and 3 or 4) was reported, although a percentage increase for
each individual risk factor was not. For individuals with 0, 1, 2, and 3 or 4 risk factors, the percentage of
intimal surface covered with fatty streaks in the aorta was 19.1%, 30%, 38%, and 35%, respectively (p for
trend = .01). In the coronary arteries, 1.3%, 2.5%, 8%, and 11%, respectively (p for trend = .01) was
involved with fatty streaks and 0.6%, 0.7%, 2.4%, and 7.2%, respectively was involved with collagenous
fibrous plaques (p for trend = .003). In the coronary arteries, the extent of fatty-streak lesions was 8.5x as
great for individuals with three or four risk factors versus those with no risk factors (p = .03) and the
extent of fibrous-plaque lesions in the coronary arteries was 12x as great (p = .006).
Reference(s):
Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between
multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa
Heart Study. N Engl J Med. 1998;338:1650-1656.
Halpern A, Mancini MC, Magalhães ME, et al. Metabolic syndrome, dyslipidemia, hypertension and type
2 diabetes in youth: from diagnosis to treatment. Diabetol Metab Syndr. 2010 Aug 18;2:55.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of
overweight and obesity in adults: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2013; available at:
http://circ.ahajournals.org.
Page 47 of 69
49. What of the following statements is CORRECT regarding ramifications of children/adolescents
being overweight or obese?
A. They are twice as likely to become overweight or obese adults as their non-obese peers.
B. They are 3 times as likely as to become overweight or obese adults as their non-obese peers.
C. They are 5 times as likely as to become overweight or obese adults as their non-obese peers.
D. They are 7 times as likely as to become overweight or obese adults as their non-obese peers.
E. There are no long-term risks for children who are overweight or obese.
Answer: C
Rationale:
Estimates from the NHANES indicate approximately one third of children in the U.S. are overweight or
obese, with approximately 17% meeting criteria for obesity, as measured by a BMI score ≥95th percentile.
Overweight or obese preschoolers are five times as likely as to become overweight or obese adults as
their non-obese peers. In an analysis of the literature, all included studies consistently report an increased
risk of overweight and obese youth becoming overweight adults, suggesting that the likelihood of
persistence of overweight into adulthood is moderate for overweight and obese youth. Because of the
effects of obesity on insulin resistance, weight loss is an important therapeutic objective for overweight or
obese individuals who are at risk for diabetes. Therefore, preventing obesity early in life is a public
health priority to improve health across the lifespan of an individual.
Reference(s):
Singh AS, Mulder C, Twisk JW, van Mechelen W, Chinapaw MJ. Tracking of childhood overweight into
adulthood: a systematic review of the literature. Obes Rev. 2008;9:474-488.
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity and trends in body mass index among
US children and adolescents, 1999–2010. JAMA 2012;307:483–90.
Norris SL, Zhang X, Avenell A, et al. Long-term effectiveness of weight-loss interventions in adults with
pre-diabetes: a review. Am J Prev Med. 2005;28:126–139
Pulgaron ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities.
Clin Ther. 2013;35:A18–32.
50. Potential negative psychological outcomes in overweight children include all of the following
EXCEPT:
A. High self-esteem
B. Depressive symptoms
C. Poor body image
D. Attention-deficit hyperactivity disorder
E. Sleep problems
Answer: A
Rationale:
Page 48 of 69
A systematic review of the literature concluded the health consequences of childhood obesity have
significant short-term and long-term adverse medical and psychosocial effects extending into adulthood.
These include health-related physical outcomes, such as high blood pressure; high cholesterol; metabolic
syndrome; type 2 diabetes; orthopedic problems; sleep apnea; asthma; and fatty liver disease, as well as
psychological, social, and behavioral consequences, such as risk for problems related to body image; self-
esteem; social isolation and discrimination; depression; and reduced quality of life.
Reference(s):
Reilly JJ , Methven E , McDowell ZC , et al. Health consequences of obesity. Arch Dis Child.
2003;88:748–752.
Pulgaron ER. Childhood obesity: a review of increased risk for physical and psychological comorbidities.
Clin Ther. 2013;35:A18–32.
Case 4 Continuation
51. You recommend to ERL’s mother that she focus on lifestyle modifications for her son. Lifestyle
modifications for managing CMR include:
A. Healthful diet
B. Weight loss
C. Calorie restriction
D. Increased physical activity
E. All of above
Answer: E
Rationale:
The primary treatment of elevated CMR is lifestyle modification. This includes regular exercise (3 to 5
days per week; 30 to 60 minutes per day), coupled with improved diet/nutrition, and weight reduction
through caloric restriction of at least reduction of 500 kcal per day, regardless of diet composition. The
goal is to achieve a sustainable weight loss of no more than 0.5 kg per week for those who are
overweight.
Reference(s):
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
52. Strategies to reduce energy intake in children and adolescents include increasing which of the
following?
A. Consumption of high energy-density foods
B. Consumption of fruits and vegetables
C. Consumption of sugar-sweetened beverages
D. Time spent watching television and exposure to food marketed to children.
E. All of the above
Answer: B
Page 49 of 69
Rationale:
Environmental determinants of childhood obesity in the United States include shifts in food consumption,
decreases in physical activity levels, and higher levels of television viewing, with the consequent
inactivity and marketing of food to children. Intervention programs should focus on strategies that alter
the food and physical activity environments in places where children live, learn, work, and play. These
strategies include decreasing consumption of high energy-density foods, decreasing consumption of
sugar-sweetened beverages (SSBs) and red meats, and decreasing time spent watching television and
exposure to food marketed to children.
Large increases in the consumption of SSBs have coincided with the epidemics of obesity and type 2
diabetes. Results of a meta-analysis of 8 prospective cohort studies revealed a diet high in consumption of
SSBs was associated with the development of type 2 diabetes. And those individuals in the highest
(versus lowest) quintile of SSB intake had a 26% greater risk of developing diabetes.
To positively impact reduction in LDL-C, ERL’s mother can plan meals that emphasize the intake of
vegetables, fruits, and whole grains, as well as low-fat dairy products, poultry, fish, legumes, non-tropical
vegetable oils and nuts. This type of dietary pattern can be adapted to appropriate calorie requirements,
personal and cultural food preferences, and nutrition therapy for other medical conditions, including
individuals with diabetes. In addition, ERL should reduce the percent of daily calories obtained from
saturated (<7% of total calories) and trans fats.
Reference(s):
Centers for Disease Control and Prevention (CDC). CDC grand rounds: childhood obesity in the United
States. MMWR Morb Mortal Wkly Rep. 2011;60:42-46.
Malik VS, Popkin BM, Bray GA, et al. Sugar-sweetened beverages and risk of metabolic syndrome and
type 2 diabetes: a meta-analysis. Diabetes Care. 2010;33:2477–2483.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce CV
risk: a report of the American College of Cardiology American/Heart Association Task Force on
Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
53. ERL plays video games for 3-4 hours a day. According to the American Academy of Pediatrics,
what is the recommended timeframe for children to have entertainment-based screen time per day?
A. <1 hour
B. <2 hours
C. <3 hours
D. <4 hours
E. <5 hours
Answer: B
Rationale:
Page 50 of 69
An average 8-year-old spends eight hours a day using various forms of media, and teenagers often surpass
11 hours of media consumption daily. Research shows that children who spent >2 hours per day
watching television or using a computer were at increased risk of high levels of psychological difficulties,
and this risk increased if the children also failed to meet physical activity guidelines. Thus, the updated
guidelines from the American Academy of Pediatrics, children should be limited to less than two hours of
entertainment-based screen time per day and shouldn’t have TVs or Internet access in their bedrooms.
This updated guideline includes all forms of “screen media” like smart phones, tablets, TV, video games,
Twitter, Facebook. Clinicians are encouraged to take a media history and ask 2 media questions at every
well-child visit: How much recreational screen time does your child or teenager consume daily? Is there a
television set or Internet-connected device in the child's bedroom?
Reference(s):
Page AS, Cooper AR, Griew P, Jago R. Children's screen viewing is related to psychological difficulties
irrespective of physical activity. Pediatrics. 2010;126:e1011-1017.
Council on Communications and Media. Children, adolescents, and the media. Pediatrics. 2013;132:958-
961.
54. Routine physical activity has important, protective health benefits, including:
A. Improved blood glucose and lipid levels.
B. No significant change in SBP or DBP.
C. Possible increases in inflammation.
D. Increasing visceral fat accumulation.
E. No change in body weight.
Answer: A
Rationale:
Routine physical activity has important, protective health benefits. People who lead sedentary lives are at
heightened risk for developing diabetes and CV disease. In fact, roughly 35% of coronary heart disease
deaths in the U.S. can be attributed to an inactive lifestyle. Recent recommendations regarding physical
activity from various groups affirm the primary role of exercise in preventing chronic disease and in
maintaining health throughout the one’s lifetime. In addition, a considerable body of evidence shows that
consistent exercise can reduce CV disease risk by improving lipid levels, lowering blood pressure,
reducing inflammation and decreasing visceral fat accumulation. Furthermore, exercise helps control
body weight; contributes to healthy bones, muscles and joints; reduces falls and moderates fall-related
injuries among older adults; relieves symptoms of anxiety and depression and is associated with fewer
hospitalizations, physician visits and medications.
It has been suggested that in order to obtain beneficial health effects, mainly in order to reduce CV risk
factors, school-age children should participate in daily moderate to intense physical activities, for 60
minutes or more, and reduce sedentary behavior to less than two hours a day.
Reference(s):
Shephard RJ, Balady GJ. Exercise as cardiovascular therapy. Circulation. 1999;99:963-972.
Page 51 of 69
Thompson PD Buchner D, Pina IL, et al; American Heart Association Council on Clinical Cardiology
Subcommittee on Exercise, Rehabilitation, and Prevention; American Heart Association Council on
Nutrition, Physical Activity, and Metabolism Subcommittee on Physical Activity. Exercise and physical
activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the
Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the
Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity).
Circulation. 2003;107:3109–3116.
Andersen LB, Harro M, Sardinha LB. et al. Physical activity and clustered cardiovascular risk in children:
a cross sectional study - The European Youth Heart Study. Lancet. 2006;368:299–304.
Nelson ME, Rejeski WJ, Blair SN, et al. Physical activity and public health in older adults:
recommendation from the American College of Sports Medicine and the American Heart Association.
Circulation. 2007;116:1094–1105.
Physical Activity Guidelines Advisory Committee. Physical Activity Guidelines Advisory Committee
Report, 2008. Washington, DC: US Department of Health and Human Services; 2008.
http://www.health.gov/paguidelines/report/pdf/CommitteeReport.pdf. Accessed November 6, 2013.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce CV
risk: a report of the American College of Cardiology American/Heart Association Task Force on
Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
Case 4 Continuation
ERL returns 6 months later without any success with lifestyle modification. His mother made nutritious
meals and snacks, but he refused to eat them, still eating strictly snack foods and drinking sugar
sweetened beverages. And he did not want to stop playing his video games. Thus, ERL’s weight
increased 4 pounds.
55. Based upon the number of ERL’s CMR factors, you decide to test for type 2 diabetes, despite
the patient’s lack of symptoms. Criteria for testing for type 2 diabetes in asymptomatic children
(persons aged 18 years and younger) include being overweight and which of the following,
EXCEPT:
A. Caucasian race
B. African American race
C. Maternal history of diabetes or GDM during the child’s gestation
D. Family history of type 2 diabetes in first- or second-degree relative
E. Signs of insulin resistance or conditions associated with insulin resistance, such as acanthosis
nigricans, hypertension, atherogenic dyslipidemia, polycystic ovary syndrome, or small-for-
gestational age birth weight
Answer: A
Rationale:
Page 52 of 69
With the increase of type 2 diabetes in children, this group should be tested based upon certain criteria.
Criteria for testing for type 2 diabetes in asymptomatic children (persons aged 18 years and younger)
include being overweight (e.g., weight >120% of ideal for height) plus any two of the following risk
factors: family history of type 2 diabetes in first- or second-degree relative; race/ethnicity (Native
American, African American, Latino, Asian American, Pacific Islander); signs of insulin resistance or
conditions associated with insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, polycystic
ovary syndrome, or small-for-gestational-age birth weight); maternal history of diabetes or GDM during
the child’s gestation. Testing should be initiated at 10 years of age or at onset of puberty, if puberty
occurs at a younger age, and should be repeated every 3 years.
Reference(s):
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
56. Among children and adolescents, what percentage of new diabetes cases is type 2 diabetes?
A. 1%
B. 5%
C. 15%
D. 25%
E. 30%
Answer: C
Rationale:
In the 1980s, type 2 diabetes in teens was virtually unheard of. Unfortunately, over the last 30 years, the
prevalence of childhood obesity has increased dramatically in North America. This prevalence has
caused an increase in a variety of health problems, including type 2 diabetes, which previously was not
typically seen until later in life. Although the prevalence of type 2 diabetes in teens is very low, it is
estimated that 15% of new diabetes cases among children and adolescents are type 2 diabetes.
Reference(s):
SEARCH for Diabetes in Youth Study Group. The burden of diabetes mellitus among US youth:
prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006;118:1510-1518.
Springer SC, Silverstein J, Copeland K, et al; American Academy of Pediatrics. Management of type 2
diabetes mellitus in children and adolescents. Pediatrics. 2013;131:e648-e664.
Case 4 Continuation
Recent lab results reveal a FPG level of 134 mg/dL and an A1c of 7.3%. Assessment: ERL is diagnosed
with type 2 diabetes. You continue to stress ERL find an activity that he would enjoy and that would “get
him off the couch”. In addition, you recommend to his mother that she meet with a nutritionist to
determine which nutritious foods he might eat. Now that ERL is diagnosed with type 2 diabetes, other
interventions are needed.
Page 53 of 69
57. Which of the following statements is INCORRECT regarding pharmacologic intervention(s)
that are indicated to treat ERL’s type 2 diabetes and other parameters of his CMR?
A. TZDs are indicated for pediatric patients to treat hyperglycemia
B. Statins should NOT be started in an adolescent who has a LDL-C level >160 mg/dL
C. Aspirin (low dose) is NOT recommended in children or adolescents to reduce CV risk
D. Metformin and insulin are indicated for pediatric patients to treat hyperglycemia
E. All of the above
Answer: A
Rationale:
For children/adolescents with CMR factors, the initial treatment in this age-group is lifestyle
modification; however, pharmacological treatments are indicated in in the following cases: LDL-C is
persistently over 190 mg/dL although risk factors are absent; presence of risk factors, such as obesity,
hypertension or smoking and LDL-C over 160 mg/dL; and individuals with diabetes and an LDL-C over
130 mg/dL. Thus, to treat a lipid disorder, medications, such as statins, or other lipid-lowering therapies,
including bile acid–binding resins (cholestryramine), and cholesterol absorption inhibitors, each of which
are currently available for treatment of dyslipidemia in children and adolescents.
Despite the escalating rates of obesity-driven type 2 diabetes in youth, oral pharmacologic interventions
remain limited to metformin, the only FDA-approved oral hypoglycemic agent for children. If metformin
fails to achieve target goals, insulin is the other choice. Thiazolidinediones do not have an FDA-approved
indication for treating children/adolescents with type 2 diabetes.
For CV protection, low dose aspirin is recommended only for most men over the age of 50 and women
over the age of 60 with diabetes who have one or more additional heart disease risk factors. For those
with diabetes and a history of CV disease, aspirin (75-162 mg per day) is recommended in adults for
secondary prevention; however, the use of aspirin in persons under the age of 21 is contraindicated due to
the associated risk of Reye Syndrome.
Reference(s):
McCrindle BW, Urbina EM, Dennison BA, et al. Drug therapy of high-risk lipid abnormalities in children
and adolescents: a scientific statement from the American Heart Association. Circulation.
2007;115:1948–1967.
Daniels SR, Greer FR, the Committee on Nutrition. Lipid screening and cardiovascular health in
childhood. Pediatrics. 2008, 122:198-208.
Halpern A, Mancini MC, Magalhães ME, et al. Metabolic syndrome, dyslipidemia, hypertension and type
2 diabetes in youth: from diagnosis to treatment. Diabetol Metab Syndr. 2010;2:55.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Page 54 of 69
58. Which of the following statement is INCORRECT regarding the results of the TODAY Trial in
adolescents with type 2 diabetes:
A. Dyslipidemia and chronic inflammation were common in youth with type 2 diabetes and improved
over time.
B. Dyslipidemia and chronic inflammation were not commonly observed in youth with type 2 diabetes.
C. Those who failed to maintain glycemic control at the end of the trial had severe impairment of β-cell
function at baseline and experienced progressive and faster loss of β-cell function compared with
those with durable glycemic control.
D. Those who maintained glycemic control at the end of the trial had severe impairment of β-cell
function and experienced progressive and faster loss of β-cell function compared with those with
durable glycemic control.
E. A and D above
Answer: E
Rationale:
The TODAY Trial evaluated adolescents with type 2 diabetes, who were randomized to receive
metformin, metformin plus rosiglitazone (a TZD), or metformin plus ILI. Participants (N=699) were
tested periodically with an OGTT to determine insulin sensitivity, insulinogenic index or C-peptide index,
and β-cell function relative to insulin sensitivity. Study results showed the combination of metformin
plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and β-cell function
relative to insulin sensitivity during the first 6 months versus metformin monotherapy and versus
metformin plus lifestyle. Although these improvements were sustained over 48 months of the trial, the
participants who failed to maintain glycemic control had significantly lower β-cell function (~50%),
higher fasting glucose concentration, and higher A1c at randomization compared with those who did not
fail.
For those with a LDL-C >130 mg/dL or triglycerides ≥300 mg/dL, statin drugs were initiated. Various
parameters of dyslipidemia and inflammation were measured over the course of 36 months or until loss of
glycemic control, including lipids, apolipoprotein B (apoB), LDL particle size, hsCRP, homocysteine,
PAI-1, and A1c. Results showed that dyslipidemia and chronic inflammation were common in
adolescents with type 2 diabetes and worsened over time. Despite some treatment group differences in
lipid and inflammatory marker changed over time, diabetes treatment was generally inadequate to control
this worsening risk.
Reference(s):
TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle
on insulin sensitivity and β-cell function in TODAY. Diabetes Care. 2013;36:1749-1757.
TODAY Study Group. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with
type 2 diabetes: the TODAY clinical trial. Diabetes Care. 2013 Jun;36(6):1758-1764.
Page 55 of 69
Case Study #5
GRL, a 36-year old Caucasian male who is a staff sergeant in the Army, returns home from a 15-month
deployment in Afghanistan. He was stationed in the mountains in the northeast section of the country on
the Pakistani border. During his time there, his unit met resistance and were involved in intense “fire
fights” every night. Along with the intensity of battle and being at an elevation of 10,000 feet, GRL had
great difficulty in sleeping, which has continued upon his return to the U.S. He presents to you with
clinical depression, caring about nothing, including his family or those around him.
Physical exam: height, 173 cm (5’ 8”); weight, 98 kg (216 lbs); BMI, 32.7 kg/m2; waist circumference, 34
inches; SBP, 125 mmHg; DBP, 82 mmHg (average of 3 readings).
Social history: 8-12 cans of beer daily; 2 pack-a-day smoker; maintains a state of physical fitness through
daily calisthenics.
Family history: Both adopted mother and father are alive and well; he does not know the medical history
of his birth parents.
Lab results: A1c, 6.1%; fasting blood glucose, 100 mg/dL; total cholesterol, 275 mg/dL; LDL-C, 160
mg/dL; HDL-C, 33 mg/dL; triglycerides, 210 mg/dL.
Medications: None
Assessment: a 35-year old male suffering from post-traumatic stress disorder, prediabetes, and
dyslipidemia.
Questions 59-65
59. Which of the following statements is CORRECT regarding PTSD and CMR?
A. PTSD is simply a psychiatric disorder and not an important predictor for cardiac and metabolic
disorders.
B. PTSD is an isolated disorder that is only seen in combat military veterans.
C. Military veterans diagnosed with PTSD are at higher risk of developing insulin resistance and
metabolic syndrome than their counterparts without PTSD.
D. Individuals with PTSD have significantly less coronary artery disease and a lower mortality risk.
E. A and C above
Answer: C
Rationale:
PTSD is not simply a psychiatric disorder that affects combat military veterans, but is a severely disabling
neuropsychiatric anxiety disorder that develops in civilians, police officers, and others as a result of
experiencing horrifying trauma/stress. Someone may experience, witness, or be confronted with an event
or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of
self or others. The person's response involved intense fear, helplessness, or horror. PTSD is not limited
to adults; it can happen in children.
Normally one relates PTSD to combat exposure, but other traumatic experiences, such as motor vehicle,
motor vehicle accidents, and hurricanes, life-threatening illnesses, such as myocardial infarction (MI), can
Page 56 of 69
also cause PTSD. Results of a meta-analysis showed clinically significant prevalence (16%) of PTSD
symptoms after acute coronary syndromes (ACS); two-thirds of patients continue to suffer from PTSD
two years after an MI.
This traumatic stress increases the risk for inflammation-related somatic diseases and early mortality.
CMR is reflected by the increased health risks associated with stress and PTSD. As a result, obesity,
dyslipidemia, hypertension, diabetes mellitus, and CV disease are prevalent among individuals
experiencing PTSD.
Reference(s):
Vanitallie T. Stress: a risk factor for serious illness. Metabolism. 2002;51(6 suppl 1):40-45.
Tedstone JE, Tarrier N: Posttraumatic stress disorder following medical illness and treatment. Clin
Psychol Rev. 2003;23:409-448.
Spindler H, Pedersen SS: Posttraumatic stress disorder in the wake of heart disease: prevalence, risk
factors, and future research directions. Psychosom Med. 2005;67:715-723.
Abbas CC, Schmid JP, Guler E, Wiedemar L, Begré S, Saner H, Schnyder U, von Känel R. Trajectory of
posttraumatic stress disorder caused by myocardial infarction: a two-year follow-up study. Int J
Psychiatry Med. 2009;39:359–376.
Edmondson D, Richardson S, Falzon L, Davidson KW, Mills MA, Neria Y. Posttraumatic stress disorder
prevalence and risk of recurrence in acute coronary syndrome patients: a meta-analytic review. PLoS
One. 2012,7:e38915.
Edmondson D, Cohen BE. Posttraumatic stress disorder and cardiovascular disease. Prog Cardiovasc
Dis. 2013;55:548-556.
Levine AB, Levine LM, Levine TB. Posttraumatic stress disorder and cardiometabolic disease.
Cardiology. 2013;127:1-19.
60. The prevalence of CMR in military veterans who were involved in combat and suffered from
PTSD is:
A. 18%
B. 32%
C. 43%
D. 52%
E. None of the above
Answer: C
Rationale:
Overweight and obesity among male veterans with PTSD strikingly exceeds national findings. In a study
of 1,710,032 Veteran men and 93,290 Veteran women, Das et al reported that 73.0% were at least
overweight, 32.9% were classified as obese, and 3.3% were found to be morbidly obese. This finding
illustrates the pervasiveness of overweight and obesity among military veterans. In addition, the
prevalence of the CMR in those with PTSD was 43%. The rates of CMR were higher in veterans than
those observed among adults in the general population as reported in the NHANES.
Page 57 of 69
Reference(s):
Das SR, Kinsinger LS, Yancy WS Jr, et al. Obesity prevalence among veterans at Veterans Affairs
medical facilities. Am J Prev Med. 2005;28:291-294.
Heppner PS, Crawford EF, Haji UA, et al. The association of posttraumatic stress disorder and metabolic
syndrome: a study of increased health risk in veterans. BMC Med. 2009;7:1.
61. PTSD influences CMR by causing:
A. Lower mean levels of triglycerides.
B. Lower SBP/DBP.
C. Elevated FPG levels.
D. Elevated levels of HDL-C.
E. All of the above
Answer: C
Rationale:
In persons with PTSD, there is chronic, high-level SNS arousal relative to controls, which is evidenced by
elevated plasma and 24-hour urinary catecholamine levels. Those with PTSD exhibit CV sympathetic
activation with significantly higher heart rates and SBP/DBP levels relative to controls, even during sleep,
with lower respiratory sinus arrhythmia. Sympathetic arousal plays a key role in activation of the renin-
angiotensin-aldosterone system and the pathogenesis of hypertension, and CV remodeling. When
compared with data from NHANES, military veterans had higher SBP and DBP levels:
SBP (130.8 mmHg versus 122.1 [women] and 123.1 mmHg [men])
DBP (81.7 mmHg versus 71.2 mmHg [women] and 74.4 mmHg [men])
The magnitude of the sympathetic response to mental stress is associated with increasing insulin
resistance. Thus, the incidence and prevalence of CMR in military personal is remarkably high, and even
higher than in the general population. In veterans, the most common identified risk factors for CMS were
decreased levels of HDL-C (34%), CAD (21%), and diabetes (19%). The severity of PTSD symptoms
correlated with increasing various parameters of CMR. Similar to increases in BP, when compared with
data from NHANES, military veterans also tended to have:
Higher mean triglycerides (189.5 mg/dL versus 132.3 mg/dL in women; 164.0 mg/dL in men from
NHANES).
Higher FPG (106.4 mg/dL versus 98.8 mg/dL [women] and 103.4 mg/dL [men])
Lower HDL (42.7 mg/dl versus 55.8 mg/dL [women] and 45.3 mg/dL [men]).
Reference(s):
Loucks EB, Magnusson KT, Cook S, Rehkopf DH, Ford ES, Berkman LF. Socioeconomic position and
the metabolic syndrome in early, middle, and late life: evidence from NHANES 1999–2002. Ann
Epidemiol. 2007;17:782–790.
Jakovljević M, Babić D, Crncević Z, Martinac M, Maslov B, Topić R. Cardiovascular manifestations of
posttraumatic stress disorder. Psychiatr Danub. 2008;20:406-410.
Page 58 of 69
Heppner PS, Crawford EF, Haji UA, et al. The association of posttraumatic stress disorder and metabolic
syndrome: a study of increased health risk in veterans. BMC Med. 2009;7:1.
Institutes of Medicine of the National Academies. Treatment for posttraumatic stress disorder in military
and veteran populations: Initial assessment. Available at www.iom.edu/militaryptsd. Accessed
November 7, 2013.
Levine AB, Levine LM, Levine TB. Posttraumatic stress disorder and cardiometabolic disease.
Cardiology. 2013;127:1-19.
62. Which of the following statements is CORRECT regarding the relationship between PTSD,
CMR, and depression or psychiatric disorders?
A. There is no relationship between PTSD and CMR on the development of depression.
B. PTSD is associated with increased rates of affective disorders, anxiety disorders, and substance abuse.
C. Women who have PTSD are twice as likely to develop a major depression.
D. Men who have PTSD are three times as likely to develop depression.
E. CMR was present in 25% of war veterans with PTSD, and approximately half had co-morbid
depression.
Answer: B
Rationale:
PTSD is associated with increased rates of affective disorders, anxiety disorders, and substance abuse.
Results of the National Comorbidity Survey indicate that at least one additional psychiatric disorder is
present in 88.3% of men and 79.0% of women who have a history of PTSD. In addition, 59% of men and
44% of women who have PTSD meet the criteria for three or more psychiatric diagnoses. Women who
have PTSD are approximately 4 times as likely to develop a major depression and greater than 4 times as
likely to develop mania as women who do not have PTSD. Men who have PTSD are approximately 7
times as likely to develop depression and more than 10 times as likely to develop mania as men who do
not have PTSD.
In military personnel, a variety of factors predispose these individuals to increased risk of developing
CMR. High levels of stress, depression, poor sleep quantity and quality as well as unhealthy lifestyle
habits such as tobacco use and restricted physical exercise, have all been linked to increased CV disease.
Despite growing evidence, there is a lack of awareness of the roles of these additional risk factors among
physicians treating military patients. Increasing knowledge of the relationship between these conditions
and CMR will enable physicians to initiate a multi-targeted approach to impact outcomes in a positive
nature.
Psychological factors are independently associated with an increased risk of both diabetes and CV
disease. These factors include depressive and anxiety symptoms, hostility, anger, and pessimism. Rates
of CMR in patients with a psychiatric disorder is remarkably high, with 72% in patients with PTSD, 60%
in those with schizophrenia, 58% in those with mood disorder, and 56% in those with dementia. This
relationship can be partially correlated to PTSD and its effects on increasing those psychological factors.
Page 59 of 69
The relationship between PTSD and CMR in military service personnel is multifaceted and the
mechanisms seem to be associative rather than direct. However, a study identified CMS in 25% of war
veterans with PTSD, and approximately half of these patients had co-morbid depression (47.8%).
Reference(s):
Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National
Comorbidity Survey. Arch Gen Psychiatry. 1995;52:1048–60.
Brady KT, Killeen TK, Brewerton T, Lucerini S. Comorbidity of psychiatric disorders and post-traumatic
stress disorder. J Clin Psychiatry. 2000;61(suppl 7):22–32.
Phillips B. Sleep-disordered breathing and cardiovascular disease. Sleep Med Rev. 2005;9:131-140.
Jakovljević M, Babić D, Crncević Z, Martinac M, Maslov B, Topić R. Cardiovascular manifestations of
posttraumatic stress disorder. Cohen BE, Panguluri P, Na B, Whooley MA. Psychological risk factors
and the metabolic syndrome in patients with coronary heart disease: findings from the Heart and Soul
Study. Psychiatry Res. 2010;175:133-137.
63. Individuals who use tobacco should be reminded that:
A. No matter how long they’ve smoked, their health will improve upon quitting.
B. Smoking aggravates cardiometabolic problems.
C. The risk of heart disease remains the same if they are long-time smokers.
D. Both a and b
E. All of the above
Answer: D
Rationale:
The deleterious effects of smoking are well known. About one in five deaths from CV diseases is
attributable to smoking. And approximately 35,000 to 40,000 non-smokers die each year from CV
disease as a result of exposure to environmental tobacco smoke. Research shows smoking aggravates
cardiometabolic problems and doubles the risk for CV disease in patients with diabetes and increases the
risk of neuropathy, nephropathy and possibly retinopathy in people with diabetes. The risk of heart
disease is cut in half just one year after quitting. After 5 to 15 years without smoking, the patient’s CV
risk is comparable to someone who never smoked.
Reference(s):
Ockene JK, Kuller LH, Svendsen KH, Meilahn E. The relationship of smoking cessation to coronary
heart disease and lung cancer in the Multiple Risk Factor Intervention Trial (MRFIT). Am J Public
Health. 1990;80:954–958.
American Heart Association. “Cigarette Smoking and Cardiovascular Disease” Fact Sheet. Available at:
http://www.heart.org/HEARTORG/GettingHealthy/QuitSmoking/QuittingResources/Smoking-
Cardiovascular-Disease-Heart-Disease_UCM_305187_Article.jsp. Accessed November 21, 2013.
Saudek CD, Margolis S. Diabetes. Johns Hopkins White Paper. Johns Hopkins Medical Institutions,
2003.
Page 60 of 69
Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and
lipoprotein profiles: a meta-analysis. Prev Med. 2003;37:283–290.
Case 5 Continuation
Based upon recommendations from the Association’s Standards of Care, you refer GRL to a mental
health specialist. Although he does not have diabetes, he has CMR factors that could predispose him to
develop type 2 diabetes. Indications for referral to a mental health specialist (familiar with diabetes
management) may include gross disregard for the medical regimen (by self or others), depression,
possibility of self-harm, debilitating anxiety (alone or with depression), indications of an eating disorder,
or cognitive functioning that significantly impairs judgment.
Page 61 of 69
Case Study #6
JH is a 54-year-old female who presents to you with complaints of a severe skeletomuscular shoulder pain
secondary to surgical repair of an AC separation and broken collarbone.
Family history: Mother is alive and has type 2 diabetes; underwent CABG at age 56 and a PCI with stent
placement at age 72. Father died at age 76 from an M.I.
Social history: Denies tobacco use, exercises only occasionally, and does not pay attention to her
nutrition.
Physical exam: blood pressure, 135/77 mmHg; BMI, 27 kg/m2; height, 5’4” (162.5 cm); waist
circumference, 36 inches (91.4 cm).
Laboratory results: total cholesterol level, 210 mg/dL; LDL-C, 156 mg/dL; HDL-C, 39 mg/dL;
triglyceride, 145 mg/dL; FPG, 104 mg/dL; A1c, 6.2%.
Current medications: none
Assessment: female with skeletomuscular shoulder pain and newly diagnosed dyslipidemia and
prediabetes; a family history of type 2 diabetes and coronary artery disease.
Questions 64-71
64. JH has lipid levels that have increased significantly since her last appointment 18 months ago.
You discuss with her prescribing medication to manage her cholesterol levels. When evaluating
this patient’s target goal in the management of cholesterol, which of the following is/are true?
A. LDL-C goals are different depending on category of risk (e.g., 0–1 risk factors, multiple risk factors,
people with CHD or risk equivalent like diabetes)
B. Cholesterol should be checked every year for patients >20 years of age
C. Ordering a non-fasting lipid panel is preferred to gauge the patient’s total cholesterol, LDL-C, HDL-
C and triglycerides
D. A normal triglyceride level is <100 mg/dL
E. All of the above
Answer: A
Rationale:
JH has CMR based upon her physical exam and lab results. Patients with at CMR or type 2 diabetes have
an increased prevalence of lipid abnormalities, contributing to their high risk of CV disease. Thus it is
important to monitor lipids to minimize adverse outcomes. For patients >20 years of age, cholesterol
should be checked every 5 years. Ordering a fasting lipid panel is preferred to gauge the patient’s total
cholesterol, LDL-C, HDL-C and triglycerides, and monitor for risk factors, which include SBP/DBP
>140/90 mmHg; HDL-C <40 mg/dL (in men); family history of myocardial infarction before age 55: in
males, >45 years; in females, >55 years.
Number of Risk Factors Recommended LDL-C Level
0-1 risk factor <160 mg/dL
Page 62 of 69
Multiple (2+) risk factors <130 mg/dL
People with overt CV disease <100 mg/dL
According to the ATP-III and the Association’s Standards of Care, aggressive lowering of LDL-C is
recommended for patients with known risk of CV disease to achieve levels <100 mg/dL, or if very high
risk, as low as 70 mg/dL; target HDL-C >40 mg/dl for men, >50 mg/dL for women; and triglycerides
<150mg/dL. Conversely, the recent ACC/AHA guidelines on the management of cholesterol do not
recommend titrating therapies to a specific LDL-C target level. Rather, they recommend monitoring
overall patient risk score once prescribed lipid-lowering therapy, specifically a statin.
The ACC/AHA guidelines recommend for individuals with diabetes who are 40 to 75 years of age, a
moderate-intensity statin (a drug that lowers LDL-C by 30% to 49%) should be used, whereas a high-
intensity statin is a reasonable choice if the patient also has a 10-year risk of atherosclerotic CV disease
>7.5%.
Reference(s):
Expert Panel on Detection Evaluation Treatment of High Blood Cholesterol In Adults (Adult Treatment
Panel III) Executive Summary of The Third Report of The National Cholesterol Education Program
(NCEP). JAMA. 2001:2486–2497.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood
cholesterol to reduce atherosclerotic CV risk in adults: A report of the American College of
Cardiology/American Heart Association. Circulation 2013; available at: http://circ.ahajournals.org.
65. Based upon JH’s waist circumference and waist-to-height ratio, she has visceral obesity. Which
of the following proinflammatory markers can be measured to determine level of CMR?
A. Adiponectin
B. hs-CRP
C. IL-6
D. Plasminogen activator inhibitor-1
E. All of the above
Answer: E
Rationale:
Inflammation is a potential mechanism linking obesity and CMR. Excess abdominal fat is believed to
increase blood levels of free fatty acids, which can inhibit the regulation of glucose by insulin. Visceral
obesity is also characterized by a proinflammatory, prothrombotic state with elevated levels of CRP,
cytokines and other proteins that may promote heart disease. CRP concentrations are elevated
predominantly in obese individuals who are also insulin resistant.
Page 63 of 69
An unfavorable inflammatory status has been shown to be negatively associated with metabolic health in
obese (BMI >30 kg/m2) and overweight (BMI <30 kg/m2) individuals. Other molecules thought to play a
role in development of insulin resistance and increased risk of CV disease include PAI-1 and fibrinogen.
Research shows metabolically unhealthy obese and non-obese individuals present with higher
concentrations of these various cytokines, including CRP, TNF-α, IL-6, and PAI-1, and lower levels of
adiponectin compared to their metabolically healthy counterparts.
Reference(s):
Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–126.
Ballantyne CH, Nambi V. Markers of inflammation and their clinical significance. Atherosclerosis.
2005;6:21–29.
McLaughlin T et al. Differentiation between obesity and insulin resistance in the association with C-
reactive protein. Circulation. 2002;106:2908–2912.
McLaughlin T, Lamendola C, Coghlan N, Liu TC, Lerner K, Sherman A, Cushman SW. Subcutaneous
adipose cell size and distribution: Relationship to insulin resistance and body fat. Obesity (Silver
Spring). 2012 Nov 29:NA. doi: 10.1002/oby.20209. [Epub ahead of print]
Davidson MH. Emerging therapeutic strategies for the management of dyslipidemia in the patients with
the metabolic syndrome. Am J Cardiol. 2004;93(11):3–11.
Phillips CM, Perry IJ. Does inflammation determine metabolic health status in obese and nonobese
adults? J Clin Endocrinol Metab. 2013;98:E1610-1619.
66. CRP is an emerging marker of inflammation and may provide useful information to assess the
risk of CV disease. Which of the following statements is/are true?
A. CRP is an independent predictor of inflammation, insulin resistance and future CV disease events in
patients with and without established CV disease.
B. Patients with low CRP levels have 1.5 to 4 times the risk of myocardial infarction than those with
high CRP levels.
C. Elevated CRP levels are not influenced by smoking, chronic inflammation, obesity and estrogen.
D. All of the above
E. None of the above
Answer: A
Rationale:
Studies have consistently found CRP to be an independent predictor of inflammation, insulin resistance
and future CV disease events in patients with and without established CV disease. Individuals with
elevated CRP levels (>2.0 mg/L) have 1.5 to 4 times the risk of myocardial infarction than those with low
CRP levels. Some studies suggest that high CRP levels in the setting of low LDL-C impart the same
level of CVD risk as high LDL-C levels in the setting of low CRP. CRP levels are more likely to be
elevated in obese, insulin resistant patients.
The updated guidelines on atherosclerotic CV risk use CRP as a differentiator for assessing individuals
with higher risk assessments to determine management strategies.
Page 64 of 69
Reference(s):
Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115–126.
Ballantyne CH, Nambi V. Markers of inflammation and their clinical significance. Atherosclerosis.
2005;6:21–29.
McLaughlin T et al. Differentiation between obesity and insulin resistance in the association with C-
reactive protein. Circulation. 2002;106:2908–2912.
Davidson MH. Emerging therapeutic strategies for the management of dyslipidemia in the patients with
the metabolic syndrome. Am J Cardiol. 2004;93:3–11.
Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of
cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
67. Which of the following statements is CORRECT regarding adiponectin?
A. Is important because of its anti-inflammatory, anti-diabetic and anti-atherogenic properties
B. Higher adiponectin levels are associated with insulin resistance.
C. Is not important in mediating CMR factors.
D. None of the above
E. All of the above
Answer: A
Rationale:
Adiponectin is the only known anti-inflammatory protein whose circulating levels are decreased before
type 2 diabetes. Insulin resistance and obesity are both associated with lower plasma adiponectin
concentrations. Results of one study showed insulin-resistant subjects had significantly lower adiponectin
concentrations (p < .001), in both obese and non-obese subjects as compared with either obese or non-
obese insulin-sensitive subjects.
Reference(s):
Abbasi F, Chu JW, Lamendola C, et al. Discrimination between obesity and insulin resistance in the
relationship with adiponectin. Diabetes. 2004;53:585-590.
Case 6 Continuation
68. You order a CRP level; results come back as 3.4 mg/L (high). Which intervention(s) would you
recommend for JH?
A. Aspirin
B. Statins
C. Increased physical activity
D. All of the above
E. None of the above
Answer: D
Page 65 of 69
Rationale:
Despite ongoing uncertainty about the value of assessing markers of inflammation or hypercoagulation,
interventions that target these abnormalities have been shown to reduce CMR. Aspirin therapy has a
strong role in CV disease prevention, especially in men, older women, and people with multiple CV
disease risk factors. Guidelines recommend increased physical activity because evidence shows
consistent exercise can reduce risk of CV disease by improving lipid levels, lowering blood pressure,
reducing inflammation and decreasing visceral fat accumulation, positively impacting inflammatory
markers, such as CRP. And statins are recommended for individuals with diabetes aged 40 to 75 years
with LDL–C levels between 70 to189 mg/dL, with or without evidence of clinical atherosclerotic CV
disease, which includes acute coronary syndromes, or a history of MI, stable or unstable angina, coronary
or other arterial revascularization, stroke, TIA, or peripheral arterial disease presumed to be of
atherosclerotic origin.
Reference(s):
USPSTF. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale.
Ann Inter Med. 2002;136:157-160.
Thompson PD, Buchner D, Pina IL, et al; American Heart Association Council on Clinical Cardiology
Subcommittee on Exercise, Rehabilitation, and Prevention; American Heart Association Council on
Nutrition, Physical Activity, and Metabolism Subcommittee on Physical Activity. Exercise and physical
activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the
Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the
Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity).
Circulation. 2003;107:3109–3116.
Poirier P et al. Obesity and Cardiovascular Disease: Pathophysiology, Evaluation, and Effect of Weight
Loss. An Update of the 1997 American Heart Association Scientific Statement on Obesity and Heart
Disease From the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.
Circulation. 2006;113:898–918.
Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary
prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized
controlled trials. JAMA. 2006;295:306-313.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce
cardiovascular risk: a report of the American College of Cardiology American/Heart Association Task
Force on Practice Guidelines. Circulation 2013; available at: http://circ.ahajournals.org.
69. JH has prediabetes and a family history of diabetes. Which of the following statements
regarding aspirin is CORRECT for individuals at high risk for CV events?
A. Aspirin is beneficial for primary prevention of CV events in individuals with no previous history of
vascular disease and a low risk of CV disease.
B. Aspirin is recommended only for women with prediabetes who are not at increased risk for
gastrointestinal tract, intracranial, or other bleeding.
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C. The use of aspirin in the primary prevention of vascular events should be considered on a case by
case basis depending upon absolute risks of the patient (i.e., age, gender, family history of premature
vascular disease).
D. The appropriate aspirin dose for primary prevention is 325 mg once daily.
E. Aspirin may reduce cerebrovascular events in persons with diabetes irrespective of CRP level.
Answer: B
Rationale:
Aspirin has been shown to be effective for secondary prevention of CV morbidity and mortality in high-
risk patients. However, two randomized controlled trials investigated the beneficial effects of aspirin
specifically in patients with diabetes failed to show a significant reduction in CV disease endpoints.
These results raise further questions about the efficacy of aspirin for primary prevention in people with
diabetes.
Based upon results from the Antithrombotic Trialists’ Collaboration study, aspirin significantly reduced
coronary heart disease events in men but not in women; however, it had no effect on stroke in men but
significantly reduced stroke in women. For secondary prevention, gender differences on the effects of
aspirin have not been observed. The Association’s Standards of Care recommend the use of aspirin
therapy (75–162 mg/day) as a secondary prevention strategy in those with diabetes who have a history of
CV disease; however, aspirin not recommended for those at low CV disease risk, as the low benefit is
likely to be outweighed by the risks of significant bleeding. The American Association of Clinical
Endocrinologists’ guidelines recommend aspirin for all persons with prediabetes who are not at increased
risk for gastrointestinal tract, intracranial, or other bleeding.
In a subanalysis of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD)
study, results revealed for those not taking aspirin, the incidence of cerebrovascular events was higher in
those individuals with diabetes who had an elevated CRP level (>0.1 mg/L) versus those with a low CRP
level (<0.1 mg/L). However, for those taking aspirin, no significant difference was noted in the incidence
of the cerebrovascular events between the high CRP group and the low CRP group. Thus, aspirin therapy
may reduce cerebrovascular events in persons with diabetes who have an elevated CRP level.
Advanced glycation end products (AGE) and/or their receptors are significantly positively correlated with
adiposity, inflammation, dyslipidemia, and insulin resistance in adults. In the Targeting Inflammation
Using Salsalate for Type-2 Diabetes (TINSAL-T2D) study, salsalate, a non-acetylated salicylate, lowed
plasma glucose levels in participants with type 2 diabetes and positively influence markers of
inflammation, decreasing levels of AGE (e.g., CRP and TNF-α) and increasing levels of adiponectin.
Reference(s):
Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet
therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ.
2002;324:71-86.
Berger JS, et al. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-
specific meta-analysis of randomized controlled trials. JAMA. 2006;295:306-313.
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Ogawa H, Nakayama M, Morimoto T, et al; Japanese Primary Prevention of Atherosclerosis with Aspirin
for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic
events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134–2141
Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes
(POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients
with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840.
Pignone M, Alberts MJ, Colwell JA, et al; American Diabetes Association; American Heart Association;
American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in
people with diabetes: a position statement of the American Diabetes Association, a scientific statement
of the American Heart Association, and an expert consensus document of the American College of
Cardiology Foundation. Diabetes Care. 2010;33:1395-1402.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
Soejima H, Ogawa H, Morimoto T, et al; JPAD Trial Investigators. Aspirin possibly reduces
cerebrovascular events in type 2 diabetic patients with higher C-reactive protein level: subanalysis from
the JPAD trial. J Cardiol. 2013;62:165-170.
Rosenzweig JL, Ferrannini E, Grundy SM, et al; Endocrine Society. Primary prevention of cardiovascular
disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline.
J Clin Endocrinol Metab. 2008;93:3671-3689.
Barzilay JI, Jablonski KA, Fonseca V, et al; the TINSAL T2D Research Consortium. The impact of
salsalate treatment on serum levels of advanced glycation end products in type 2 diabetes. Diabetes
Care. 2013 Nov 19. [Epub ahead of print]
70. JH asks about the risk of bleeding with aspirin. Which of the following statements is correct
regarding the risk of MAJOR bleeding (gastrointestinal or intracranial) from aspirin use, especially
in persons with diabetes?
A. Major bleeding is observed only at doses greater than 325 mg per day.
B. There is no significant increase in major bleeding in individuals with diabetes who take aspirin.
C. Major bleeding is not an issue in patients at high risk of a CV event
D. Diabetes is associated with an increased risk of major bleeding episodes only in those taking aspirin.
E. None of the above
Answer: B
Rationale:
Therapy with low-dose aspirin is used for the treatment of CV disease. It is recommended as a secondary
prevention measure for individuals with moderate to high risk of CV events, that is, for patients with
multiple risk factors such as hypertension, dyslipidemia, obesity, diabetes, and family history of ischemic
heart disease. However, any benefit may be outweighed by the risks of significant bleeding. But is this
true for individuals with diabetes when compared to those without?
In a population-based cohort that compared individuals being treated with low-dose aspirin (<300
mg/day) versus matched controls without aspirin use, results showed aspirin use was associated with a
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greater risk of major bleeding in most of the subgroups investigated; however, there was no significant
increase in major bleeding in individuals with diabetes. For participants with diabetes, there was an
associated increase risk of major bleeding episodes irrespective of aspirin use. Thus, those with diabetes
had a high rate of bleeding that was not independently associated with aspirin use.
Reference(s):
Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet
therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ.
2002;324:71-86.
Pignone M, Alberts MJ, Colwell JA, et al; American Diabetes Association; American Heart Association;
American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in
people with diabetes: a position statement of the American Diabetes Association, a scientific statement
of the American Heart Association, and an expert consensus document of the American College of
Cardiology Foundation. Diabetes Care. 2010;33:1395-1402.
American Diabetes Association. Standards of Medical Care in Diabetes—2014 Diabetes Care.
2014;37:S14-S80.
71. Matching Question.
In discussing the management of her cholesterol levels, JH asks what are the different types of
medications and how do they work. Match the class of drugs with the appropriate mechanism of
action.
Drug Class Mechanism
A. Statins ___ Activates an enzyme that enhances the
breakdown of triglyceride-rich lipoproteins while
increasing HDL-C
B. Cholesterol absorption inhibitors ___ Reduces the liver’s ability to produce VLDL
C. Fibrates ___ Lowers LDL-C by reducing the amount of
cholesterol absorbed in the intestines and increases
LDL receptor activity.
D. Niacin ___ Binds to bile acids in the intestines and prevent
their reabsorption, leading to increased hepatic
LDL-C removal from the blood.
E. Resins ___ Increasing hepatic LDL-C removal from the
blood.
Answer: C, D, B, E, A
Rationale:
Niacin reduces the liver’s ability to produce VLDL. At a dose of 1 to 2 g per day it has been shown to
increase HDL-C levels by 15% to 30% and decrease triglycerides. However, evidence from clinical
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outcome trials, which included concomitant statin therapy, failed to show any benefit with niacin. The
AIM-HIGH trial, a secondary prevention trial in patients with low HDL-C and elevated triglycerides that
added extended-release niacin to simvastatin (and ezetimibe as needed to achieve LDL-C goals), was
stopped owing to the clinical futility for demonstrating event reduction, despite significant HDL-C
increases and a significant event rate.
Fibrates activate an enzyme that enhances the breakdown of triglyceride-rich lipoproteins while
increasing HDL-C. These drugs lower triglycerides while raising HDL-C approximately 10% to 20%,
effects thought to occur via peroxisome proliferator-activated receptor alpha activation. However, in the
lipid arm of ACCORD, adding fenofibrate to simvastatin did not improve the primary CV end point.
Cholesterol absorption inhibitors lower LDL-C by reducing the amount of cholesterol absorbed in the
intestines and increase LDL receptor activity.
Resins bind to bile acids in the intestines and prevent their reabsorption, leading to increased hepatic
LDL-C removal from the blood.
Statin therapy has proven risk reduction in both primary and secondary prevention of cardiovascular
disease. Statin monotherapy has been shown to reduce LDL cholesterol and triglycerides by 18–55% and
7–30%, respectively, and increase HDL by 5–15%. Currently, statins remain the first-line therapy among
individuals with low HDL-C levels and significant CV risk who warrant intervention.
Reference(s):
Expert Panel on Detection, Evaluation, Treatment of High Blood Cholesterol In Adults (Adult Treatment
Panel III) Executive Summary of The Third Report of the National Cholesterol Education Program
(NCEP). JAMA. 2001:2486–2497.
Lincoff AM, Wolski K, Nicholls SJ, Nissen SE. Pioglitazone and risk of cardiovascular events in patients
with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007;298:1180–1188.
Ginsberg HN, Elam MB, Lovato LC, et al; ACCORD Study Group. Effects of combination lipid therapy
in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–1574.
Mihaylova B, Emberson J, Blackwell L, et al; Cholesterol Treatment Trialists’ (CTT) Collaborators. The
effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-
analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590.