Towards Diabetes Prevention - Saint Agnes Medical Center. DiabetesPrevention2… · Towards...
Transcript of Towards Diabetes Prevention - Saint Agnes Medical Center. DiabetesPrevention2… · Towards...
Towards Diabetes PreventionTowards Diabetes Prevention
Leigh Perreault, MDAssociate Professor of Medicine
Endocrinology, Metabolism and DiabetesUniversity of Colorado Anschutz Medical Campus
Associate Professor of EpidemiologyColorado School of Public Health
Leigh Perreault, MDAssociate Professor of Medicine
Endocrinology, Metabolism and DiabetesUniversity of Colorado Anschutz Medical Campus
Associate Professor of EpidemiologyColorado School of Public Health
Diabetes Care 2008
Preventing Diabetes in People at Highest Risk
CDC Statement
January 26, 2011
“An estimated 79 million Americans - 35% of the population over 20 years of age - currently has pre-
diabetes.”
Screening
• Everyone >45 years old
• Anyone with a BMI>25 kg/m2 + 1 risk factor
• Risk factors: *physical inactivity *FDR with diabetes *high-risk ethnicity *women delivering a baby >9 lbs or h/o GDM or PCOS *HDL<35, TG> 250 mg/dl
*history of hypertension or CVD
American Diabetes Association: Glucose criteria for pre-diabetes
NGT IFG
IGT IFG/IGT
Fasting glucose (mg/dl)
2h glucose (mg/dl)
<100 100-125
<140
140-200
A1c = 5.7-6.4%
Risk of Diabetes for those withPre-diabetes
A1c(%)
Annual incidence of diabetes (%)
5
6
7
8
5 10 15 20 2520
25%/5 year risk
50%/5 year risk
Zhang, Diabetes Care 2010
Intervention Trials to Reduce Progression of IGT to Type 2 Diabetes
Rosi
FDPS2 DPP9DaQing1
DPP3
Lifestyle
Troglitazone
Non-thiazolidinedione Thiazolidinediones
Pio
DPP2
Met
IDPP4
Met Acarbose Orlistat
XEN-DOS6IDPP4
STOP-NIDDM5
ACTNOW11DREAM10
1Pan XR et al: Diabetes Care 20:537-544; 1997. 2Tuomilehto J et al: N Engl J Med 344:1343-1350; 2001. 3DPP Research Group: N Engl J Med 346:393-403; 2002. 4Ramachandran A et al: Diabetologia 49:289-297; 2006. 5Chiasson JL et al: Lancet 359:2072-2207; 2002. 6Torgerson JS et al: Diabetes Care27: 155-161; 2004. 7Holman RR et al: N Engl J Med 362:1463-1476; 2010. 8Buchanan TA et al: Diabetes 51:2796-2803; 2002. 9DPP Research Group:Diabetes 54:1150-1156; 2005. 10DREAM Trial Investigators: Lancet 368:1096-1105; 2006. 11DeFronzo RA et al: N Engl J Med 364:1104-1115; 2011.
Nateg
NAVIGATOR7
62%†
55%†
75%† 72%†
*vs control†vs placebo
58%*
42%*
58%†
29%†31%†
26%* 25%†
37%†
-7%
TRIPOD8
Diabetes Prevention Program (DPP)
Knowler, NEJM 2002
• Lose >7% body weight• Exercise 150 minutes/week• Consider metformin• Re-screen annually
Diabetes Care 2007
Diabetes Prevention Program Outcomes Study (DPPOS)
Knowler, Lancet 2010
0 1 2 3 4 5 6 7 8 9 10
intervention
intervention observation
The Alternate Explanation: Quasi-inertia
Pre-diabetes DiabetesNormoglycemia
The Alternate Explanation: Quasi-inertia
Pre-diabetes DiabetesNormoglycemia
New Goals for People with Pre-diabetes: Normal Glucose Regulation
Perreault, Lancet 2012
56%
Benefit of Maintaining NGR
Perreault, Lancet 2012
Does treatment modality matter?
Perreault, Lancet 2012
American Diabetes Association: Glucose criteria for pre-diabetes
NGT IFG
IGT IFG/IGT
Fasting glucose (mg/dl)
2h glucose (mg/dl)
<100 100-125
<140
140-200
QuickTime™ and a decompressor
are needed to see this picture.
QuickTime™ and a decompressor
are needed to see this picture.
Can we do a better job preventing diabetes by targeting defects specific
to the subtypes of pre-diabetes?
Can we do a better job preventing diabetes by targeting defects specific
to the subtypes of pre-diabetes?
Matschinsky, Medicine Reports 2010
Hepatic Glucokinase
GlucoseG-6-P
glucokinase
G-6-Pase
Hepatic GlucokinaseGKRP
GlucoseG-6-P
glucokinase
G-6-Pase
Hepatic Glucokinase
GlucoseG-6-P
GKRP glucokinase
G-6-Pase
fructose
Demographics
NGT IFG
N= 17 17
M/W 8/9 8/9
BMI (kg/m2) 31±0.6 32±1.0
% Fat 37±1.5 36±2.2
Fasting glucose (mg/dl) 91±0.9* 102±1.1
2-hour glucose (mg/dl) 90±6.1* 111±6.1
*p<0.05 from IFG
Study Design
6,6 2H2-glucose isotope
somatostatin, glucagon, growth hormone, insulin
glucose
Hours0 2 5 7 9
fructose
*
*p<0.05 from IFG
#p<0.05 from prior stage
##
*
*p<0.05 from IFG#p<0.05 from prior stage
#
##
#p<0.05 from prior stage
##
#
0.75%
What’s changed in the past 50 years?
• Portion size explosion• High-fructose corn syrup• Trans fat• Processed foods• Environmental pollutants
Increasing Prevalence of Diabetes Tracks with Environmental Pollutants
Neel, Diabetes 2011
Diabetes Tracks with Gut Microbial Composition
Qin, Nature 2012
microbial gene clusters -T2DM microbial gene clusters +T2DM
Increasing Prevalence of Diabetes Tracks with Sleep Disorders:
NHANES 2008T2DM Sleep Disorders
Will achievement of normoglycemia improve outcomes in pre-diabetes? Will achievement of normoglycemia improve outcomes in pre-diabetes?
Can Glucose Lowering in Pre-diabetes Prevent Macrovascular Complications?
UKPDS ADVANCE VA-DT ACCORD
% re
duct
ion
in c
ompo
site
mac
rova
scul
ar d
isea
se
16%6% 12% 10%
None significant
Data from trials in type 2 diabetes
Glucose Lowering Decreases Carotid Intima Media Thickness in Pre-diabetes
PlaceboPioglitazone
Xiang, Athero 2008
PlaceboPioglitazone
Xiang, Athero 2008
DeFronzo, NEJM 2011
Carotid Intima-Media Thickness
Mea
n %
Cha
nge
0
2
4
Months0 12 24 36
p=0.047
PlaceboPioglitazone
Glucose Lowering Decreases Carotid Intima Media Thickness in Pre-diabetes
Chiasson, JAMA 2003
Glucose Lowering Decreases CVD in Pre-diabetes
49%
Should we expand our focus on CVD prevention to those with pre-diabetes? Should we expand our focus on CVD
prevention to those with pre-diabetes?
Conclusions
• Pre-diabetes represents a very high-risk state for diabetes and carries a higher incidence of related complications in and of itself.
• Prevention of diabetes - particularly when NGR can be attained - is key to lower risk.
• Additional risk can also be decreased through CVD risk stratification, but guidelines for lipid and BP goals specific to pre-diabetes are lacking.
• Consider the subtype of pre-diabetes when picking a glucose-lowering strategy.
• NGR should be the treatment goal with patients monitored for relapse.
• Applying lipid and BP standards-of-care in diabetes to pre-diabetes may be even more important than NGR for CVD prevention.
Bringing the Data to Patient Care
• Bryan Bergman, PhD
• Anna Kerege
• Samantha Bacon
• Richard Hamman, MD, DrPh
• Diabetes Prevention Program
• National Institutes of Health (5U01-DK048375-12)
Thank you!