Vipul Lakhani, MD Oregon Medical Group Endocrinology · 2015. 11. 12. · Vipul Lakhani, MD Oregon...

Vipul Lakhani, MD

Oregon Medical Group

Endocrinology

Disclosures

None

Objectives

Be able to diagnose diabetes and

assess control

Be able to identify appropriate classes of

medications for diabetes treatment

Begin to manage diabetes and co-

morbidities

Epidemiology of Diabetes

Diabetes affects 29.1 million people of all ages

9.3% of the U.S. population

Diagnosed: 21 million

Undiagnosed: 8.1 million

Leading cause of kidney failure, nontraumatic lower-limb amputation, new cases of blindness among adults

Major cause of heart disease and stroke

Seventh leading cause of death

National Diabetes Statistics Report, 2014. Available at: http://www.diabetes.org/diabetes-basics/statistics/?loc=db-slabnav/

www.cdc.gov

County-Level Estimates of Diagnosed Diabetes (%), Adults ≥20 years, 2008

Percent

0 - 6.5

6.6 - 8.0

8.1 - 9.4

9.5 - 11.1

> 11.2

0 – 6.5

6.6 – 8.0

8.1 – 9.4

9.5 – 11.1

≥ 11.2

Number of Americans with Diagnosed Diabetes, 1980-2009

www.cdc.gov

STANDARDS OF MEDICAL CARE IN DIABETES—2015

ADA Evidence Grading System for Clinical Practice

Recommendations

Level of Evidence

Description

A Clear or supportive evidence from adequately powered well-conducted, generalizable, randomized controlled trials

Compelling nonexperimental evidence

B Supportive evidence from well-conducted cohort studies or case-control study

C Supportive evidence from poorly controlled or uncontrolled studies

Conflicting evidence with the weight of evidence supporting the recommendation

E Expert consensus or clinical experience

ADA. Diabetes Care 2015;38(suppl 1):S2; Table 1

Recommendations: Strategies for Improving Diabetes Care

ADA. 1. Strategies for Improving Diabetes Care. Diabetes Care 2015;38(suppl 1):S5

Care should be aligned with components of the Chronic Care Model to ensure productive interactions between a prepared proactive practice team and an informed activated patient A

When feasible, care systems should support team-based care, community involvement, patient registries, and embedded decision support tools to meet patient needs B

Physicians, nurse practitioners, physician’s assistants, nurses,

dietitians, pharmacists, mental health professionals, CDE

In this collaborative and integrated team approach, essential that individuals with diabetes assume an active role in their care

CLASSIFICATION AND DIAGNOSIS OF DIABETES

Classification of Diabetes

Type 1 diabetes

β-cell destruction

Type 2 diabetes

Progressive insulin secretory defect

Other specific types of diabetes

Genetic defects in β-cell function, insulin action (MODY)

Diseases of the exocrine pancreas (CFRD)

Drug- or chemical-induced

Gestational diabetes mellitus (GDM)

ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S8

Criteria for the Diagnosis of Diabetes

A1C ≥6.5%

OR

Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L)

OR

2-h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an OGTT

OR

A random plasma glucose ≥200 mg/dL (11.1 mmol/L)

ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S9; Table 2.1

FPG 100–125 mg/dL (5.6–6.9 mmol/L): IFG

OR

2-h plasma glucose in the 75-g OGTT 140–199 mg/dL (7.8–11.0 mmol/L): IGT

OR

A1C 5.7–6.4%

*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range.

ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S10; Table 2.3

Categories of Increased Risk for Diabetes (Prediabetes)*

Recommendations: Testing for Diabetes in Asymptomatic Patients

Consider testing overweight/obese adults (BMI ≥25 kg/m2 or ≥ 23 kg/m2 in Asian Americans) with one or more additional risk factors for type 2 diabetes; for all patients, particularly those who are overweight, testing should begin at age 45 years B

If tests are normal, repeat testing at least at 3-year intervals is reasonable C

To test for diabetes/prediabetes, the A1C, FPG, or 2-h 75-g OGTT are appropriate B

In those with prediabetes, monitor for development of diabetes annually E

ADA. 2. Classification and Diagnosis. Diabetes Care 2015;38(suppl 1):S11

PREVENTION/DELAY OF TYPE 2 DIABETES

Recommendations: Prevention/Delay of Type 2 Diabetes

Diabetes Prevention Program

Targeting weight loss of 7% of body weight

Increasing physical activity to at least 150 min/week

of moderate activity (eg, walking)

Follow-up counseling appears to be important

for success

Based on cost-effectiveness of diabetes

prevention, such programs should be covered

by third-party payers

ADA. 5. Prevention/Delay of Type 2 Diabetes. Diabetes Care 2015;38(suppl 1):S31

GLYCEMIC TARGETS

ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S33

Diabetes Care: Glycemic Control

Two primary techniques available for health providers and patients to assess effectiveness of management plan on glycemic control Patient self-monitoring of blood glucose (SMBG), or

interstitial glucose

A1C

Perform the A1C test at least two times a year in patients meeting treatment goals (and have stable glycemic control)

Perform the A1C test quarterly in patients whose therapy has changed or who are not meeting glycemic goals

Approach to the Management of Hyperglycemia

ADA. 6. Glycemic Targets. Diabetes Care 2015;38(suppl 1):S37. Figure 6.1; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

Lowering A1C to below or around 7% has been shown to reduce microvascular complications and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease. Therefore, a reasonable A1C goal for many nonpregnant adults is <7%

Providers might reasonably suggest more stringent A1C goals (such as <6.5%) for selected individual patients, if this can be achieved without significant hypoglycemia

Recommendations: Glycemic Goals in Adults (1)


Recommendations: Glycemic Goals in Adults (2)

Less stringent A1C goals (such as <8%) may be appropriate for patients with

History of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbid conditions

Those with longstanding diabetes in whom the general goal is difficult to attain despite DSME, appropriate glucose monitoring, and effective doses of multiple glucose lowering agents including insulin


APPROACHES TO GLYCEMIC TREATMENT

Recommendations: Pharmacological Therapy For Type 1 Diabetes

Most people with type 1 diabetes should:

• Be treated with MDI injections (3–4 injections per

day of basal and prandial insulin) or continuous

subcutaneous insulin infusion (CSII) A

• Be educated in how to match prandial insulin

dose to carbohydrate intake, premeal blood

glucose, and anticipated activity E

• Use insulin analogs to reduce hypoglycemia risk A

ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S41

Metformin, if not contraindicated and

if tolerated, is the preferred initial

pharmacological agent for type 2

diabetes A

Recommendations: Pharmacological Therapy For Type 2 Diabetes (1)


Recommendations: Therapy for Type 2 Diabetes (2)

A patient-centered approach should be used to

guide choice of pharmacological agents

Considerations include efficacy, cost, potential side

effects, effects on weight, comorbidities,

hypoglycemia risk, and patient preferences E

Due to the progressive nature of type 2

diabetes, insulin therapy is eventually indicated

for many patients with type 2 diabetes B

Overall each class of noninsulin agent

decreases A1c by 0.9-1.1%


Antihyperglycemic Therapy in Type 2 Diabetes

ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S43. Figure 7.1; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

Approach To Starting and Adjusting Insulin in Type 2 Diabetes

ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S46. Figure 7.2; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

Case

58 yo M has had DM2 for 16 yrs, poorly controlled. Current regimen below. [+] MI and CHF. [+] retinopathy and gastroparesis. No hypoglycemia. Nonsmoker. [+] family history. BP 138/90, BMI 34. Lungs clear. [+] BLE edema.

○ Metformin 1000mg BID

○ Glipizide 10mg BID

○ Atorvastatin 40 mg daily

Case - continued

Hemoglobin A1c = 8.4%

Creatinine = 0.67 mg/dL

TSH = 2.83 mIU/L

LDL cholesterol = 92 mg/dL

Case - continued

Addition of which medication below will

improve glucose control and minimize

side effects?

A. Exenetide

B. Pioglitazone

C. Saxagliptin

D. Canagliflozin

E. Insulin glargine

Thiazolidinediones

Pioglitazone, Rosiglitazone

Activates nuclear transcription factor

PPAR-γ, increasing insulin sensitivity

Pros:

○ No hypoglycemia, ? Decreased CVD (pio),

generic

Cons:

○ Wt increase, edema, CHF, ? MI (rosi)

Glucagon-like-peptide-1 agonists

Exenetide, exenetide extended release, liraglutide, albiglutide, dulaglutide

Increases glucose dependent insulin secretion, increases satiety, slows gastric emptying

Pros: ○ No hypoglycemia, Dec wt, Dec postprand gluc

Cons: ○ GI side effects, ?pancreatitis, medullary

thyroid cancer, cost

Dipeptidyl peptidase-4 inhibitors

Sitagliptin, saxagliptin, linagliptin, alogliptin

DPP-4 breaks down GLP-1

Results in increased glucose dependent insulin secretion

Pros: ○ No hypoglycemia, oral

Cons: ○ ?increased CHF, ?acute pancreatitis,

angioedema, cost

Sodium-glucose Cotransporter 2

inhibitors

Canagliflozin, dapagliflozin,

empagliflozin

Inihibits SGLT-2 in the proximal

nephron, leading to glucosuria

Pros:

○ No hypoglycemia, wt loss, decreased BP

Cons:

○ GU infections, polyuria, hypotension,

dehydration, increased LDL, cost

Insulins (onset / duration)

Rapid acting (15’ / 3-5h) ○ Lispro

○ Aspart

○ Glulisine

○ Inhaled insulin (15’ / 2h)

Short acting (30-60’ / 4-8h) ○ Human regular

Intermediate ○ Human NPH (2-4h / 10-18h)

○ U-500 regular (30-60’ / 10-18h)

Insulins (onset / duration)

Basal insulin analogs

○ Lantus® (Glargine U-100) (4-6h / 24h)

○ Detemir (2-3h / 6-24h)

○ Toujeo® (Glargine U-300) (6h / 24h)

Pre-mixed insulins

○ 70/30

○ 75/25

○ 50/50

Case

58 yo M has had DM2 for 2 yrs, poorly

controlled. Current regimen below. No

complications. No hypoglycemia.

Nonsmoker. [+] family history. BP

128/60, BMI 31. Exam otherwise

normal.

○ Metformin 1000mg BID

○ Glipizide 10mg BID

○ Atorvastatin 40 mg daily

Case - continued




Case - continued

Addition of which medication below will

improve glucose control and minimize

side effects?

A. Liraglutide

B. Pioglitazone

C. Linagliptin

D. Canagliflozin

E. Insulin detemir

CARDIOVASCULAR DISEASE AND RISK MANAGEMENT

CVD is the major cause of morbidity, mortality for those with diabetes Largest contributor to direct/indirect costs

Common conditions coexisting with type 2 diabetes (e.g., hypertension, dyslipidemia) are clear risk factors for CVD

Diabetes itself confers independent risk

Benefits observed when individual cardiovascular risk factors are controlled to prevent/slow CVD in people with diabetes

Cardiovascular Disease

ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S49

Goals

People with diabetes and hypertension should be treated to a systolic blood pressure goal of <140 mmHg A

Lower systolic targets, such as <130 mmHg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden C

Patients with diabetes should be treated to a diastolic blood pressure <90 mmHg A

Lower diastolic targets, such as <80 mmHg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden B

Recommendations: Hypertension/Blood Pressure Control


Treatment

Pharmacological therapy for patients with diabetes and hypertension comprise a regimen that includes either an ACE inhibitor or angiotensin II receptor

blocker B;

if one class is not tolerated, substitute the other C

An ACE inhibitor or ARB is not recommended for the primary prevention of diabetic kidney disease in patients who have normal blood pressure and a normal urine-albumin-to-creatinine ratio (UACR) (<30 mg/g) B

Recommendations: Hypertension/Blood Pressure Control


Screening

In adults, a screening lipid profile is reasonable E At first diagnosis

At the initial medical evaluation

And/or at age 40 years and periodically (e.g., every 1-2 years) thereafter

Recommendations: Dyslipidemia/Lipid Management


Case

19 yo M has had DM1 for 8 yrs,

reasonable control managed on MDI

insulin regimen. No complications. Rare

hypoglycemia. Nonsmoker. [-] family

history. BP 128/78, BMI 32 otherwise

normal exam.

Case - continued



TSH = 2.83 mIU/L

Total cholesterol = 224 mg/dL

HDL cholesterol = 26 mg/dL


Triglycerides = 229 mg/dL

Case - continued

Initiation of which of the following would

lead to greatest reduction in lifetime

cardiovascular risk?

A. Intensify glucose control

B. Statin

C. Fibrate

D. Niacin

E. Low fat diet

Recommendations for Statin Treatment in People with Diabetes

Age Risk factors Recommended

statin dose*

Monitoring with lipid panel

<40 years

None None Annually or as needed to monitor for adherence

CVD risk factor(s)**

Moderate or high

Overt CVD*** High

40–75 years

None Moderate As needed to monitor adherence

CVD risk factors High

Overt CVD High

>75 years

None Moderate As needed to monitor adherence

CVD risk factors Moderate or high

Overt CVD High * In addition to lifestyle therapy.

** CVD risk factors include LDL cholesterol ≥100 mg/dL (2.6 mmol/L), high blood pressure, smoking, and

overweight and obesity.

*** Overt CVD includes those with previous cardiovascular events or acute coronary syndromes.

ADA. 8. Cardiovascular Disease and Risk Management. Diabetes Care 2015;38(suppl 1):S52, Table 8.1

What is moderate / high intensity

statin?

Circulation. June 24, 2014 vol. 129 no. 25 suppl 2 S1-S45

Treatment recommendations and goals

Combination therapy has been shown not to provide additional cardiovascular benefit above statin therapy alone and is not generally recommended A

Statin therapy is contraindicated in pregnancy B

In clinical practice, providers may need to adjust intensity of statin therapy based on individual patient response to medication (e.g. side effects, tolerability, LDL cholesterol levels.) E

Cholesterol laboratory testing may be helpful in monitoring adherence to therapy but may not be needed once the patient is stable on therapy E

Recommendations: Dyslipidemia/Lipid Management


Questions?

Vipul Lakhani, MD Oregon Medical Group Endocrinology · 2015. 11. 12. · Vipul Lakhani, MD Oregon...

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