Diabetes: What is the scope of the problem? Elizabeth R. Seaquist MD Division of Endocrinology and Diabetes Department of Medicine Director, General Clinical Research Center Pennock Family Chair in Diabetes Research University of Minnesota
Diabetes Mellitus A disorder of glucose metabolism resulting in hyperglycemia as a result of insulin deficiency or abnormal insulin secretion and action.
Impact of Type 1 and Type 2 Diabetes Individuals diagnosed by 1.3 million each year 6th leading cause of death Diabetes Increasingly affects all age groups Especially prevalent in African and Hispanic Americans Shortens average life expectancy by up to 15 years Adapted from http://www.cdc.gov/diabetes/pubs/factsheet.htm#contents. Accessed 2/10/04. Diabetes Research Working Group. NIH Pub #99-4398;1999:1 129.
Diabetes Trends* Among Adults in the U.S., (Includes Gestational Diabetes) BRFSS, 1990,1995 and 2001 1990 1995 2001 No Data <4% 4-6% 6-8% 8-10% >10% Source: Mokdad et al., Diabetes Care 2000;23:1278-83; J Am Med Assoc 2001;286:10.
2002 Diabetes prevalence in US by age, gender, race 30 Prevalence per 100 people 25 20 15 10 5 0-44 45-64 65-74 >75 0 White male White female Black male Black female Hispanic male Hispanic female CDC
Gestational diabetes 3-5% Other 1-2% Type 1 diabetes 5-10% Type 2 diabetes 90-95%
Type 1 Diabetes Mellitus Insulin Dependent Diabetes Mellitus (IDDM), Type I Diabetes, Ketosis-prone diabetes, Juvenile onset diabetes mellitus Caused by an absolute deficiency of insulin Occurs because of autoimmune destruction of pancreatic beta cells Arises in genetically susceptible individuals exposed to a triggering factor
Type 1 diabetes Peak time of clinical onset is at puberty but can present at any age Patients are usually lean Concordance rate for identical twins is ~50% Insulin therapy is required for survival
Type 2 Diabetes Mellitus Non-insulin dependent diabetes mellitus (NIDDM), Adult onset diabetes mellitus Occurs because of a defect in both insulin secretion and insulin action Primary defect probably varies by population but failure to compensate for primary defect ultimately leads to hyperglycemia
Prentki, M. et al. J. Clin. Invest. 2006;116:1802-1812 Copyright 2006 American Society for Clinical Investigation
Type 2 diabetes Usually presents in adulthood Patients are usually obese at presentation Concordance rate for identical wins is >90% Long prodrome (period of impaired glucose intolerance) often undetected Long-term complications may be present at time of diagnosis
Diabetic Complications Microvascular Complications Diabetic Retinopathy Macrovascular Complications Stroke Diabetic Nephropathy Heart Disease Diabetic Neuropathy Peripheral Vascular Disease Harris MI. Clin Invest Med 1995;18:231-239 Nelson RG et al. Adv Nephrol Necker Hosp 1995;24:145-156 World Health Organization, 2002;Fact Sheet N 138
Effect of Glycemic Control on Incidence of Diabetic Complications in Patients With Type 1 Diabetes Estimated Lifetime Cumulative Incidences Conventional Therapy Intensive Therapy Difference Between Therapies 100 Microalbuminuria 80 60 40 20 0-20 -40-60 Proliferative Retinopathy Blindness Albuminuria Nephropathy End-stage renal disease Neuropathy Neuropathy Data derived from Rathmann W. Drug Benefit Trends. 1998;24 33.
Food Exercise Glucose Control Drugs
Hirsch I. N Engl J Med 2005;352:174-183
Typical course for type 2 diabetes Usual sequence Year of interventions 0 4 7 10 16 20 Diet Oral Agents Combination Therapy with Oral agents Insulin Usual Clinical Course Onset of Diabetes Diagnosis Development of complications Death
Role of Incretins in Glucose Homeostasis Ingestion of food GI tract Release of gut hormones Incretins 1,2 Active GLP-1 & GIP DPP-4 enzyme Pancreas 2,3 Glucose-dependent Insulin from beta cells (GLP-1 and GIP) Beta cells Alpha cells Glucose dependent Glucagon from alpha cells (GLP-1) Glucose uptake by muscles 2,4 Glucose production by liver Blood glucose Inactive GLP-1 Inactive GIP DPP-4 = dipeptidyl-peptidase 4 1. Kieffer TJ, Habener JF. Endocr Rev. 1999;20:876 913. 2. Ahrén B. Curr Diab Rep. 2003;2:365 372. 3. Drucker DJ. Diabetes Care. 2003;26:2929 2940. 4. Holst JJ. Diabetes Metab Res Rev. 2002;18:430 441.
Incretin therapies GLP-1 analog (Exenatide) Administered twice daily by subcutaneous injection Lowers A1c 0.5-1.0% Side effects are weight loss, nausea, hypoglycemia DPP-1 inhibitors (vitagliptin, sidagliptin) Orally administered once a day Lowers A1c by ~0.5% Not associated with weight loss or nausea
Economic Consequences of Diabetes in the United States Direct Costs: $92 Billion Indirect Costs: $40 Billion Annual Total: $132 Billion* Indirect costs due to disability and early mortality: $40 billion Excess prevalence of general medical conditions: $44 billion Diabetes/ diabetes supplies: $23 billion Excess prevalence of chronic complications: $25 billion *Approximate 2002 US Dollars Hogan P, et al. Diabetes Care. 2003;26:917 932.
Total Per Capita Health Care Expenditure 2002 14,000 13,243 12,000 $ 10,000 8,000 6,000 4,000 2,560 2,000 0 Diabetes Without Diabetes ADA. Diabetes Care. 2003;26:917 932.