Diabetes Day for Primary Care Clinicians Advances in Diabetes Care

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Diabetes Day for Primary Care Clinicians Advances in Diabetes Care Elliot Sternthal, MD, FACP, FACE Chair New England AACE Diabetes Day Planning Committee

Welcome and Introduction This presentation will: Define obesity, prediabetes, and diabetes Discuss the diagnoses and management of obesity, prediabetes, and diabetes Explain the early risk factors for diabetes and the rationale for aggressive treatment to delay or prevent diabetes onset

Prevalence (%). Overweight and Obesity Prevalence Increasing Among U.S. Adults 87.5 70. Overweight Obesity 52.5 35. 17.5 0. 1960-62 1971-74 1976-80 1988-94 1999-2002 2003-2004 2009-2010 NHANES Data Collection Period NHANES = National Health and Nutrition Examination Survey. Flegal KM et al. JAMA 2002;288:1723-27; Hedley AA et al. JAMA 2004;291:2847-50; Ogden CL et al. JAMA 2006;295:1549-55; Flegal KM et al. JAMA 2012;307(5):491-7.

Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among US Adults Obesity (BMI 30 kg/m 2 ) 1994 2000 2013 No Data <14.0% 14.0% 17.9% 18.0% 21.9% 22.0% 25.9% > 26.0% Diabetes 1994 2000 2013 No Data <4.5% 4.5% 5.9% 6.0% 7.4% 7.5% 8.9% >9.0% BMI = body mass index; CDC = U.S. Center for Disease Control and Prevention. CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics

Garvey W et al. Endocrine Practice 2016;22 (Suppl 3):1-203; Cawley J et al. PharmacoEconomics 2015;33:707-722; 2014 AACE/ACE Consensus Conference on Obesity. Executive Summary. Available at: http://mms.businesswire.com/media/20140325006164/en/408761/1/aace.pdf An Expensive Epidemic Currently, 69% of American adults are overweight or obese and nearly 38% are obese Compared to non-obese individuals, obesity adds $3,559 per patient to total annual health care costs This includes $1,130 per patient to annual pharmacy costs As much as 27.5% of annual medical spending in the U.S. is obesity-related In the U.S., medical costs for obesity are at least $190.2 billion per year Some studies estimate current obesity-related costs as high as $315.8 billion

Obesity and Metabolic Syndrome: A Cluster of Coronary Heart Disease Risk Factors Diet, physical inactivity and stress All potentiate genetic susceptibility to obesity Prothrombotic State Atherogenic Dyslipidemia Genetic Susceptibility Obesity Insulin Resistance Raised Blood Pressure Autonomic Dysfunction Proinflammatory State High-Density Small Low-Density Triglycerides Lipoprotein Cholesterol Lipoprotein Particles Adapted from Grundy SM. J Clin Endocrinol Metab. 2005;89:2595-2600. Slide Source: Obesityonline.org

Obesity, Insulin Resistance, Metabolic Syndrome, and the Natural History of Type 2 Diabetes Genetics, environment, and lifestyle (obesity, inactivity, poor diet) Impaired fasting glucose Decreased β-cell function Insulin resistance Impaired glucose tolerance Ominous octet T2DM Ongoing hyperglycemia DEATH Ongoing, worsening macrovascular and microvascular complications Hypertension Endothelial dysfunction Hyperinsulinemia HDL-C, Triglycerides Eye, nerve, and kidney damage Atherosclerosis Myocardial infarction Cardiovascular event Blindness Chronic renal failure Amputation Disability HDL-C = high density lipoprotein-cholesterol; T2DM = type 2 diabetes mellitus.

Progression to Diabetes Over 3 to 5 years, 25% of patients with prediabetes will develop diabetes, while 50% will remain in the category of IFG or IGT; 25% will have normal glucose tolerance. Overall incidence: 4% to 10%/year IFG = impaired fasting glucose; IGT = impaired glucose tolerance; UK = United Kingdom. American Diabetes Association. Diabetes Care. 2003;26:917-932.; Nathan D, et al. Diabetes Care. 2007;30(3):753-759.

Diabetes Prevention Program: Weight Loss For Reduced Diabetes Incidence Analysis of 2-year outcomes from the Diabetes Prevention Program (DPP) showed the importance of weight loss. Weight loss over 2 years is strongest predictor of: Reduced diabetes incidence (HR 0.90 per kg, 95% CI 0.87, 0.93; P < 0.01) Improved fasting glucose (β = -0.57 mg/dl per kg, 95% CI -0.66, -0.48; P < 0.01) Weight cycling (repeated weight loss and gain) was associated with increased diabetes incidence. DPP = Diabetes Prevention Program; HR = heart rate. Delahanty LM. Diabetes Care. 2014. [Epub ahead of print].

Achieving Normal Glucose Tolerance Markedly Delays Future Overt Diabetes ~50% risk reduction If normal glucose levels are reached, only ~18% risk 6 years after study DPP = Diabetes Prevention Program; DPPOS = Diabetes Prevention Program Outcomes Study; NGR = normal glucose regulation. Perreault L, Pan Q, Mather KJ, et al. Lancet. 2012;379(9833):2243-51.

Benefits of Weight Loss Weight loss produces several benefits for patients with prediabetes or diabetes Improved insulin resistance Improved plasma lipids Decreased hypertension

A1C and Complications: UKPDS A1C = glycated hemoglobin; UKPDS = United Kingdom Prospective Diabetes Study Group. UKPDS Group. Lancet. 1998;352:837-853.

The Impact of Intensive Therapy in T2DM: Summary of Major Clinical Trials Subset evaluations show reduced CV outcomes if shorter duration of T2DM without significant pre-existing complications Initial Trial Long-term Follow-up Study Microvascular Macrovascular Mortality UGDP UKPDS DCCT/EDIC* ACCORD (unadjusted) (adjusted) ADVANCE VADT *T1DM study. ACCORD = Action to Control Cardiovascular Risk in Diabetes; ADVANCE = Action in Diabetes and Vascular Disease; CV = cardiovascular; DCCT = Diabetes Control and Complications Trial; EDIC = Epidemiology of Diabetes Interventions and Complications; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; UGDP = University Group Diabetes Project; UKPDS = United Kingdom Prospective Diabetes Study Group; VADT = Veterans Affairs Diabetes Trial. (UKPDS) Group. Lancet. 1998;352:854-865.; Duckworth W, et al. N Engl J Med. 2009;360.; Gerstein HC. Lancet. 2014;[Epub ahead of print]; Gerstein HC, et al. N Engl J Med. 2008;358:2545-2559.; Goldner MG. JAMA. 1971;218(9):1400-1410.; Holman

A1C The ABCs of Diabetes Care: Recommended Goals ADA and IDF recommend < 7.0% in general, < 6.0% in selected individuals. AACE/ACE recommend 6.5% in patients without concurrent serious illness and at low hypoglycemia risk, and > 6.5% in patients with concurrent serious illness and at risk for hypoglycemia. Blood Pressure AACE/ACE and IDF recommend < 130/80 mm Hg ADA recommends <140/90 mm Hg Cholesterol AACE/ACE (and previously ADA-now age +ASCVD/RF) recommend LDL-C: < 100 mg/dl (< 70 mg/dl in very high risk patients) HDL-C: > 40 mg/dl in men and > 50 mg/dl in women Non HDL-C: < 130 mg/dl (< 100 mg/dl in high-risk patients) Triglycerides: < 150 mg/dl A1C = glycated hemoglobin; AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; ADA = American Diabetes Association; HDL-C = high density lipoprotein-cholesterol; IDF = International Diabetes Federation; LDL-C = low density lipoprotein-cholesterol. American Diabetes Association. Diabetes Care. 2016;39 Suppl 1:S1-102; Handlesman Y et al. Endocr Pract. 2015; 21 Suppl 1:1-87; IDF Clinical Guidelines Task Force. Global Guideline for Type 2 Diabetes. Available at: http://www.idf.org/sites/default/files/idf- Guideline-for-Type-2-Diabetes.pdf

Summary Obesity as a disease Obesity and medical complications Relationship to diabetes Prediabetes Early intervention: prevention or delay of diabetes Diabetes and related complications Treating the ABCs of diabetes The purpose of AACE Primary Care Day: We can do better We must do better