Diabetes UpdateDiabetes Update

Division of EndocrinologyDivision of EndocrinologyDepartment of MedicineDepartment of Medicine

Wayne State University Medical SchoolWayne State University Medical SchoolDetroit, Michigan Detroit, Michigan

Part 1 of 3

DiabeticRetinopathy

Leading causeof blindnessin adults

DiabeticNephropathy

Major cause of kidney failure

CardiovascularDisease

Stroke

DiabeticNeuropathy

Major cause of lower extremity amputations

CV Disease & Stroke account for ~65% of deaths in T2D patients

Type 2 Diabetes Associated with Serious Complications

CV = cardiovascular.National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States, 2005. Bethesda, MD: U.S. Department of Health and Human Services, National Institute of Health, 2005.

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Cost ($ billions)

42% Of Diabetes Costs Related To Hospitalization 42% Of Diabetes Costs Related To Hospitalization And Long-Term CareAnd Long-Term Care

$200 Billion $200 Billion Total!Total!

2010 US Total Healthcare Costs Attributable To Diabetes

5050

4040

3030

2020

1010

00Direct CostsDirect Costs Indirect CostsIndirect Costs‡‡

Oral AntidiabeticsInsulin and SuppliesOutpatient Medication*Outpatient Services†

Physician Office VisitsNursing Home Care (11%)Inpatient Care (31%)

ADA and AACE/ACE Guidelines:Treatment Goals for A1C, FPG, and PPG

ParameterNormal1,2

LevelADA3 Goal

AACE/ACE2

Goal

FPG, mg/dL <100 90–130 <110

PPG, mg/dL <140 <180 <140

A1C, % 4–6 <7a ≤6.5

FPG=fasting plasma glucose; PPG=postprandial glucose; ADA=American Diabetes Association; AACE=American Association of Clinical Endocrinologists; ACE=American College of Endocrinology.

1. Adapted from Buse J et al. In: Williams Textbook of Endocrinology. 10th ed. 2003. Permission requested.2. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007;13:(suppl 1)3–68. 3. ADA. Diabetes Care. 2007;30:S4–S41.

aThe goal for an individual patient is to achieve an A1C as close to normal (<6%) as possible without significant hypoglycemia.aThe goal for an individual patient is to achieve an A1C as close to normal (<6%) as possible without significant hypoglycemia.

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Components of HbA1cComponents of HbA1c

HbA1c = FBS + PPBS

6

Both Fasting and Postprandial Hyperglycemia Contribute to A1CBoth Fasting and Postprandial Hyperglycemia Contribute to A1C

Plasma Glucose (mg/dL)

Adapted from Riddle MC. Diabetes Care. 1990;13:676-686

300

200

100

0

Time of Day

6 AM 12 PM 6 PM 12 AM 6 AM

Normal glycemic exposure

A1C ~5%

Uncontrolled DiabetesWith A1C ~8%

PostprandialHyperglycemia

Fasting Hyperglycemia

Normal Physiology

DEMAND SUPPLY

HyperglycemiaHyperglycemia

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Type 2 Diabetes Is a Complex and Progressive Metabolic Disorder

1. Kendall DM, et al. International Diabetes Center. 2005. 2. DeFronzo DA. Diabetes. 2009. 3. Fehse F, et al. J Clin Endocrinol Metab. 2005.

Adapted from Kendall DM, Bergenstal RM.

History and Progression of Type 2 Diabetes1-3

By the time of diabetes onset,

up to 80% of beta-cell function

may be lost2,3

Diagnosis

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Unmet Needs for Type 2 DM Treatment

Durable HbA1c control (i.e. help improve Beta-cell function).

Addressing islet dysfunction (i.e., addressing both insulin and glucagon secretion.

Addressing both fasting and postprandial sugars

Minimum risk of treatment-limiting adverse events:

-Minimum risk of hypoglycemia

-Minimum risk of weight gain

-No increased risk of edema

-No increased risk of heart failure