Diabetes: What is the scope of the problem?

Elizabeth R. Seaquist MD Division of Endocrinology and Diabetes

Department of MedicineDirector, General Clinical Research Center

Pennock Family Chair in Diabetes ResearchUniversity of Minnesota

Diabetes MellitusA disorder of glucose metabolism resulting in hyperglycemia as a result of insulin deficiency or abnormal insulin secretion and action.

Shortens average Shortens average life expectancy life expectancy

by up to 15 yearsby up to 15 years

Especially prevalent in Especially prevalent in African and Hispanic African and Hispanic

AmericansAmericans

Impact of Type 1 and Type 2 Diabetes

DiabetesDiabetes

6th leading 6th leading cause of death cause of death

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.

Individuals Individuals diagnoseddiagnosed

byby 1.3 1.3 million each million each

yearyear

Increasingly Increasingly affects all age affects all age

groupsgroups

Source: Mokdad et al., Diabetes Care 2000;23:1278-83; J Am Med Assoc 2001;286:10 .

Diabetes Trends* Among Adults in the U.S.,(Includes Gestational Diabetes)BRFSS, 1990,1995 and 20011990 1995

2001

No Data <4% 4-6% 6-8% 8-10% >10%

0

5

10

15

20

25

30

White male Whitefemale

Black male Black female Hispanicmale

Hispanicfemale

Pre

vale

nce

per

10

0 p

eo

ple

0-44

45-64

65-74

>75

2002 Diabetes prevalence in US by age, gender, race

CDC

Type 2 diabetes90-95%

Type 1 diabetes5-10%

Other1-2%

Gestational diabetes

3-5%

Type 1 Diabetes MellitusInsulin 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 MellitusNon-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

Copyright ©2006 American Society for Clinical Investigation

Prentki, M. et al. J. Clin. Invest. 2006;116:1802-1812

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

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

Diabetic Retinopathy

Microvascular Complications Macrovascular Complications

Diabetic Complications

Diabetic Nephropathy

Diabetic Neuropathy

Stroke

PeripheralVascular Disease

HeartDisease

Effect of Glycemic Control on Incidence of Diabetic Complications in Patients With Type 1

Diabetes

-60

-40-20

020

40

6080

100Conventional Therapy Intensive Therapy Difference Between Therapies

Data derived from Rathmann W. Drug Benefit Trends. 1998;24–33.

Estim

ated

Life

time

Cum

ulat

ive

Inci

denc

es

Proliferative

Blindness

Microalbuminuria

AlbuminuriaEnd-stage

renal disease

NeuropathyNephropathyRetinopathy

Neuropathy

Food Exercise

Glucose Control

Drugs

Hirsch I. N Engl J Med 2005;352:174-183

Usual sequence of interventions

0 4 7 10 16 20

Diet OralAgents

CombinationTherapy withOral agents

Insulin

UsualClinicalCourse

Year

Onset ofDiabetes

Diagnosis Development ofcomplications

Death

Typical course for type 2 diabetes

Glucose uptake

by muscles2,4

Role of Incretins in Glucose Homeostasis

DPP-4 = dipeptidyl-peptidase 41. 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.

Ingestion of food

Beta cellsAlpha cells

Release of gut hormones — Incretins1,2

Pancreas2,3

Glucose-dependentInsulin from beta cells

(GLP-1 and GIP)

Glucose production

by liver

Blood glucose

Glucose dependentGlucagon fromalpha cells

(GLP-1)

GI tractActive

GLP-1 & GIP

DPP-4 enzyme

Inactive GIP

Inactive GLP-1

Incretin therapies• GLP-1 analog (Exenatide)

Administered twice daily by subcutaneous injectionLowers A1c 0.5-1.0%Side effects are weight loss, nausea, hypoglycemia

• DPP-1 inhibitors (vitagliptin, sidagliptin)Orally administered once a dayLowers A1c by ~0.5%Not associated with weight loss or nausea

Economic Consequences of Diabetes in the United States

Indirect Costs:Indirect Costs: $40 Billion$40 Billion

Annual Total: $132 Billion*Annual Total: $132 Billion*

Indirect costs due to disability

and early mortality:$40 billion

*Approximate 2002 US Dollars

Diabetes/diabetes supplies:$23 billion

Direct Costs:Direct Costs: $92 Billion$92 Billion

Excess prevalence of

general medical conditions:$44 billion

Excessprevalence of chronic

complications:$25 billion$25 billion

Hogan P, et al. Diabetes Care. 2003;26:917–932.

Total Per Capita Health Care Expenditure 2002

13,243

2,560

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

$

Diabetes Without DiabetesADA. Diabetes Care. 2003;26:917–932.