Why Do We Care About Prediabetes?
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- Darcy Reed
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1 Why Do We Care About Prediabetes? Complications of Diabetes Diabetic Retinopathy Leading cause of blindness in adults 1,2 Diabetic Nephropathy Leading cause of Kidney failure Stroke 2- to 4-fold increase in stroke Cardiovascular Disease 8/10 individuals with diabetes die from CV events 6 Diabetic Neuropathy Leading cause of non-traumatic lower extremity amputations 7,8
2 Cardiovascular Risk in Prediabetes Ralph A. DeFronzo, Muhammad Abdul-Ghani Am J Cardio, 2011; 108, SB,3B 24B
3 Risk of Vascular Death According to Fasting Glucose
4 Prevalence of Microvascular Complications in Prediabetes Retinopathy 8%. Higher with combined IFG/IGT Chronic Kidney Disease 17% IFG 12% NGT Neuropathy 7.4% NGT 11.3% IFG 13% IGT Milman S & Crandall J. Med Clinic NA 2011;95:
5 Glucose is a Continuous Variable Risk for retinopathy by glucose values
6 Prediabetes and Cognition Glucose levels in the prediabetes range are associated with decreased memory and decreased hippocampal volume 1 Inverse association with higher levels of FPG and cognitive function 2 Prediabetes is associated with decreased brain volume and lower performance on executive functioning 3 1. Kerti L Neurology 2013;81: Anderson C et al. Diab Res Clin Practice. 2009;83: Tan Z et al. Diab Care 2011; 34:
7 Diabetes and Prediabetes is Associated with Higher Rates of Hospitalizations Schneider A et al. Diab Care 2016;39:
8 3. Papanas N et al Nat Rev Endocrinol 2011; 7: Why Screen for Pre-diabetes? Provision of intensive lifestyle intervention (DPP) delayed diagnosis of diabetes by 2-3 years, had decreased need for medications and better control of hypertension and hyperlipidemia Of newly diagnosed diabetes: 10 20% have retinopathy 2 10% have neuropathy % have chronic kidney disease 2
9 Screening for Dysglycemia All adults 45 years of age or older All overweight adults (BMI with at least one of the the risk factors Children ( 18 years of age) who are at or above 85 th %ile for weight for height plus two of the following (starting at age 10 or puberty) High risk ethnicity First or second degree relative with diabetes Signs of insulin resistance (acanthosis nigricans, hypertension, dyslipidemia, PCOS, small for gestational ages) Mother with history of diabetes or gestational diabetes with child s gestation If results are normal, testing should be repeated at a minimum of 3- year intervals, with consideration of more frequent testing depending on initial results (e.g., those with prediabetes should be tested yearly) and risk status. ADA Standards of Medical Care. Diab Care 39 (Suppl 1): S1-S112
10 Results of Screening for Prediabetes In NHANES , 73% of U.S. adults met ADA criteria for screening for dysglycemia (156 million) About 51% reported being screened in previous 3 years. A sample of all patients were screened for dysglycemia in the study Markedly fewer patients of highest risk by ethnicity were screened by their usual care provider Among those tested, dysglycemia was noted in 59% of those reported being tested and 50% of those who did not undergo routine testing. (diabetes was found in 6%) Risk factors with highest predictive value: history of prediabetes, gestational diabetes, age 45 years, hypertension, family history of diabetes Bullard KM et al. (2015) PLoS ONE 10(4): e doi: /journal. pone
11 Low Rate of Documentation of Prediabetes in Primary Care In an EMR chart review: About 40 50% of people had documentation of screening for prediabetes Fewer than 1% of patients meeting criteria for prediabetes had diagnosis in problem list Mainous A et al. J Am Board Fam Med 2016;29:
12 Diabetes Prevention Program (DPP) Diabetes Prevention Program (DPP) Knowler et al, NEJM 2002;346: Knowler, NEJM 2
13 Diabetes Prevention Program Outcomes Study (DPPOS) DPPOS Results intervention Years Since Randomization intervention observation Knowler et al. Lancet 2010
14 Benefit of Maintaining NGR Benefits of Maintaining Normoglycemia Perreault, Lancet 2012
15 Does treatment modality matter? Did Treatment Modality Matter? Perreault, Lancet 2012
16 Diabetes Prevention Trials Perreault L & Faerch K. J Diab & Complic 2014;23:
17 Cases/100 person-years Diabetes Prevention Program: Progression to Type 2 Diabetes by BMI Placebo Metformin Intensive lifestyle 9 3% 16% 53% 51% % 61% 0 24 to <30 n= to <35 n= n=1194 Baseline BMI (kg/m 2 ) The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.
18 Characteristics of Metformin Responders in DPP years of age African American BMI 35 Fasting glucose Knowler et al, NEJM 2002;346:
19 Low Rate of Metformin Use in Prediabetes Using the United Healthcare database, 17,352 people with prediabetes between age of 18 58, not pregnant and normal renal function Only 3.9% of patients were receiving metformin 7.8% of highest risk patients (BMI 35 or women with history of GDM) Moin T et al. Ann Intern Med Apr 21; 162:
20 Pioglitazone Reduces Risk for CVA or MI in Insulin Resistant Patients with Previous CVA/TIA 42% had IFG 2 65% had A1c 5.7% 2 1. Kernan W et al. N Engl J Med 2016;374: Inzucchi S & Furie K. J Diab (accepted for publication)
21 Current and Emerging Pharmacotherapies for Weight Management in Prediabetes and Diabetes David C.W. Lau, Hwee Teoh Can J of Diab, Volume 39, St 5, 2015, S134 S141
22 Liraglutide 3.0 mg Lowers Risk of Conversion from Prediabetes to Diabetes leroux C et al. Lancet 2017;389:
23 Incidence of Type 2 Diabetes (% Patients) Prevention of Type 2 Diabetes at 8 Years After Bariatric Surgery (94% Restrictive) Control Bariatric surgery Follow-up After Surgery (y) 3.6 Control Surgery Initial BMI (kg/m 2 ) Weight change at year 8: 1 11% % Sjostrom et al. Hypertension 2000;36:20.
24 Changes in cardiovascular disease risk factors over 10 years, through the end of (DPPOS). Ronald B. Goldberg, and Kieren Mather Arterioscler Thromb Vasc Biol. 2012;32: Copyright American Heart Association, Inc. All rights reserved.
25 CVD mortality in proportion of participants (%) Weight loss in patients with prediabetes reduces longterm incidence of cardiovascular mortality (Da Qing) HR 0.59, 95% CI ( ) Control Intervention Years Cumulative death incidence (%; 95% CI) Intervention (n=430) Control (n=138) Hazard ratio (95% CI) All-cause mortality 28.1% ( ) 38.4% ( ) 0.71 ( ) Cardiovascular disease mortality 11.9% ( ) 19.6% ( ) 0.59 ( ) Diabetes incidence 72.6% ( ) 89.9% ( ) 0.55 ( ) Data are n(%) unless stated otherwise. HR, hazard ratios adjusted by clinic. Li et al. Lancet Diabetes Endocrinol 2014;2: p value
26 Lifestyle Modification Reduces Risk for DM, Retinopathy and Death A 20 year follow up of the Da Qing diabetes prevention study 43% lower incidence of DM during the follow up 6 years of lifestyle intervention can prevent or delay DM for up to 14 years after the intervention was stopped. 47% reduction in the incidence of severe vision-threatening retinopathy primarily due to the reduced incidence of DM No evidence of prevention of nephropathy or neuropathy. Decreased cumulative incidence of CVD mortality (11.9% vs 19.6%) and all cause mortality (28.1% vs 38.4%) ADA Standards of Care 2016
27 % reduction in composite microvascular disease Prevention of Diabetes Prevents Composite Microvascular Disease 0% 28% Diabetes No diabetes DPP, Lancet 2015
28 % reduction in composite microvascular disease Prevention of Diabetes Prevents Composite Microvascular Disease 28% Diabetes Pre diabetes Normoglycemia Perreault, in preparation 2016
29 Probability of Any Cardiovascular Event Glucose Lowering Decreases CVD in Pre-diabetes (Stop-NIDDM) P = 0.04 (Log-Rank test) P = 0.03 (Cox Proportional Model) Placebo 49% Acarbose Days After Randomisation Chiasson, JAMA 2003
30 Direct Medical Costs of the Participants in the DPP/DPPOS by intervention The Diabetes Prevention Program Research Group Dia Care 2012;35: by American Diabetes Association
31 American Diabetes Association Standards of Care 2016 A1C of % (39 46 mmol/mol) should be informed of their increased risk for diabetes and CVD and counseled about effective strate- gies to lower their risks (see Section 4 Prevention or Delay of Type 2 Diabetes ). Similar to glucose measurements, the continuum of risk is curvilinear, so as A1C rises, the diabetes risk rises disproportionately (12). Aggressive interventions and vigilant follow-up should be pursued for those considered at very high risk (e.g., those with A1C.6.0% [42 mmol/mol]). Metformin may be recommended for high-risk individuals (e.g., those with a history of GDM, those who are very obese, and/or those with more severe or progressive hyperglycemia) and/or those with rising A1C despite lifestyle intervention.
32 DPP is Cost-Effective In view of cost (disability, premature mortality and consumption of health-care resources), attempts to reverse the increasing rates of type 2 diabetes are clearly major public-health priorities in developing as well as affluent societies Lancet. 2000; 356: 1454
33 Potential Barriers to Effective Clinical-System Based Lifestyle Intervention Programs Clinical health systems lack structure and expertise to change lifestyle. Too expensive and not scalable. Previous models of clinical based / lifestyle change have not achieved sustainable reimbursement. Waiting until people have elevated glucose is too late. Diabetes is a common-source epidemic rooted in culture and society.
34 Macro-Level Determinants Obesity and Diabetes: Current Debates Over Policy Strategies Physical environment Food environment Social environment Economy and poverty
35 Summary Prediabetes is perhaps the most common chronic disease in the US (?World) More than 50% will progress to diabetes Risk for progression can be reduced It is associated with risk for development of micro- and macrovascular disease We should be able to prevent it Doing so requires community based approaches at avoidance of sedentary behavior, poor nutrition and obesity
36 So What s The Best Way to Prevent Complications of Diabetes? PREVENT PRE-DIABETES!
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