1. Diabetes – A 21st Century Epidemic
Diagnosis and what is it
A common disease
An expensive disease
A serious disease
A treatable disease
A preventable disease

2. Diagnosis and what is it Glucose Tolerance Categories
FPG
126 mg/dL
100 mg/dL
7.0 mmol/L
5.7 mmol/L
Impaired Fasting
Glucose
Normal
2-Hour PG on OGTT
200 mg/dL
140 mg/dL
11.1
mmol/L
7.8
Diabetes Mellitus
Impaired Glucose
Tolerance
Slide 4
Glucose Tolerance Categories
Either the fasting plasma glucose (FPG) test or the 2-hour plasma glucose (PG) determination during the oral glucose tolerance test (OGTT) may be used to determine glucose tolerance status. According to the most recent diagnostic criteria established by The Expert Committee on the Diagnosis and Class- ification of Diabetes Mellitus, an FPG value 126 mg/dL (7.0 mmol/L) or a 2-hour plasma glucose value 200 mg/dL (11.1 mmol/L) are the new cutoff points for the diagnosis of diabetes. The cutoff points for the intermediate stage of hyperglycemia denoted by the terms impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) have been adjusted to conform to the new diagnostic criteria for diabetes mellitus. IFG is now defined by FPG 110 mg/dL (6.1 mmol/L) and <126 mg/dL (<7.0 mmol/L), and IGT is defined by 2-hour PG measurements 140 mg/dL (7.8 mmol/L) and <200 mg/dL (<11.1 mmol/L).
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20:
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:

3. What is it ? Diabetes is a Vascular Disease Background Retinopathy
% Affected
Fasting Plasma Glucose

4. Natural History of Type 2 Diabetes
Post-meal glucose
350
250
100
300
200
150
IGT
Diabetes
Glucose (mg/dL)
Fasting glucose
-15
-10 -5 5 10 15 20 25 75 50 25
100
125
Relative Function (%)
Insulin resistance
ß-cell
-15
-10 -5 5 10 15 20 25
Years of Diabetes
Adapted from: International Diabetes Center (Minneapolis, Minnesota). 4

5. Etiologic Classification of Diabetes Mellitus
Type 1 b-cell destruction with lack of insulin
Type 2 Insulin resistance with insulin deficiency
Other specific types Genetic defects in b-cell function, exocrine pancreas diseases, endo- crinopathies, drug- or chemical- induced, and other rare forms
Gestational Insulin resistance with b-cell dysfunction
Slide 3
Etiologic Classification of Diabetes Mellitus
Diabetes mellitus is best described as a group of metabolic diseases character- ized by hyperglycemia. The hyperglycemia may be the result of defects in insulin secretion or insulin sensitivity, or both. Two major forms of diabetes are recognized in the most recent classification scheme, which was developed by The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, an international group, and has been adopted by both the American Diabetes Association and the World Health Organization. Type 1 diabetes includes almost all cases that are marked by destruction of the pancreatic islet -cells. Type 2 diabetes includes those cases that result from insulin resistance accompanied by a defect in insulin secretion. Other specific forms of diabetes, which affect far fewer patients than the two major forms, include genetic defects of -cell function, genetic defects in insulin sensitivity, diseases of the exocrine pancreas, endocrinopathies, drug- or chemical-induced infections, uncommon immune-mediated conditions, and other genetic conditions. Gestational diabetes mellitus is a fourth type in this new classification system.
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care ;20:
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:

6. Diabetes in the U.S.
23.6 million (10.7% ≥ 20 y.o) at a cost of $174 billion in 2007
57 million with prediabetes
6th disease specific cause of death.
Leading cause of:
Kidney failure.
Adult blindness.
Nontraumatic limb amputation.
Cardiovascular disease.
ADA. Diabetes Care 31: , 2008 6

7. Diabetes is a Common Disease : Estimated Prevalence of Diabetes in the US: Adult Men and Women30
Men
Women
21.1
20.2 20
17.8
17.5
Percent of Population
12.9
12.4 10
6.8
6.1
Slide 7
Estimated Prevalence of Diabetes in the US:
Adult Men and Woman
The 1997 prevalence of diagnosed diabetes among adults aged 20 years or older was estimated using data collected in the Third National Health and Nutrition Examination Survey (NHANES III), The most recent diagnostic criteria for diabetes (fasting plasma glucose [FPG] 126 mg/dL) was applied (see Slides 4 and 5). Prevalence rates rose with age, with a plateau after age 75 years. The highest prevalence rates (17.5% to 21.1%) were found in the 60- to 74- and 75+ -year age groups.
Harris M, Flegal K, Cowie C, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. Diabetes Care. 1998;21:
1.6
1.7
20-39
40-49
50-59
60-74
75+
Age (y)
Harris, et al. Diabetes Care. 1998;21: , with permission.

8. Estimated Prevalence of Diabetes in the US: Breakdown by Ethnicity10
9.3
Diagnosed
8.2
Undiagnosed 8 6
Percent of Population
4.8
4.5 4
3.6
2.5
Slide 9
Estimated Prevalence of Diabetes in the US:
Breakdown by Ethnicity
According to estimates developed using data from the Third National Health and Nutrition Examination Survey (NHANES III), , and applying the new diagnostic criteria for diabetes (see Slides 4 and 5), estimates for the prevalence of diabetes (diagnosed and undiagnosed) were developed for adults of different ethnicities. Diabetes (diagnosed and undiagnosed) is more prevalent among African Americans and Hispanic Americans than among non-Hispanic white Americans, and the proportion of undiagnosed cases is higher.
Harris M, Flegal K, Cowie C, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. Diabetes Care. 1998;21: 2
Non-Hispanic
African
Hispanic
White
American
American
Data from Harris, et al. Diabetes Care. 1998;21:

9. Diabetes – An expensive disease
Direct and indirect costs of diabetes estimated to be $174 Billion annually in the USA in 2007
Costs to most health systems is 2-3 fold greater annually for patients with diabetes

10. 1997 Per Capita Health Care Costs: Persons With and Without Diabetes25
23.5
Diabetes
No diabetes 20 15
Annual Costs ($1000s)
12.2 10
Slide 10
1997 Per Capita Health Care Costs:
Persons With and Without Diabetes
National health care survey data from the National Center for Health Statistics were used to estimate per capita annual health care costs for persons with and without diabetes. On a per capita basis, persons with diabetes had significantly higher medical costs than did persons without this disease. Per capita inpatient costs were doubled for patients with diabetes compared to those without ($23,501 vs $12,220). Drug costs were approximately three times higher among persons with diabetes versus those without ($2,550 vs $1,457).
American Diabetes Association. Economic consequences of diabetes mellitus in the U.S. in Diabetes Care. 1998;21: 5
2.5
1.5
0.7
0.4
0.7
0.4
0.7
0.2
Inpatient
Outpatient ER
Office
Outpatient
Services
Visits
Drugs
Data from American Diabetes Association. Diabetes Care. 1998;21:

11. Diabetes – A serious but treatable disease
Microvascular complications
Blindness, renal failure and nerve dysfunction
Macrovascular complications
Atherosclerosis –MI, Stroke and amputations
Hypertension - Stroke, CHF, CAD

12. The Arterial Tree in Diabetes
Conduit Artery Resistance Precapillary Capillaries
Arterioles Arterioles
Atherosclerosis Hypertension Retinopathy Neuropathy
Nephropathy

13. Intermittent claudication
Framingham Heart Study 30-Year Follow-Up: CVD Events in Patients With Diabetes (Ages 35-64) 10 10 9
Men
Women 8 11
Risk
ratio 6 30 19 4 38 9 6 20 3* 2
Total CVD
CHD
Cardiac failure
Intermittent claudication
Stroke
Age-adjusted annual rate/1,000
P<0.001 for all values except *P<0.05.
Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease.
Ruderman N et al, eds. Oxford; 1992.

14. Women, Diabetes, and CHD Diabetic women are at high risk for CHD
Diabetes eliminates relative cardioprotective effect of being premenopausal
risk of recurrent MI in diabetic women is three times that of nondiabetic women
Age-adjusted mean time to recurrent MI or fatal CHD event is 5.1 yr for diabetic women vs 8.1 yr for nondiabetic women
Kannel WB. Am Heart J. 1985;110:
Abbott RD et al. JAMA. 1988;260:

15. Atherosclerosis in Diabetes
~80% of all diabetic mortality
75% from coronary atherosclerosis
25% from cerebral or peripheral vascular disease
>75% of all hospitalizations for diabetic complications
>50% of patients with newly diagnosed type 2 diabetes have CHD
National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995.

16. 4S: Major CHD Event Reduction in a Patients With Diabetes
Proportion without major CHD event
32%
Diabetic, simvastatin
- P=0.002
Diabetic, placebo
55%
Nondiabetic, simvastatin
- P=0.0001
Nondiabetic, placebo
Yr since randomization
Pyörälä K et al. Diabetes Care. 1997;20:

17. The Arterial Tree in Diabetes
Conduit Artery Resistance Precapillary Capillaries
Arterioles Arterioles
Atherosclerosis Hypertension Retinopathy Neuropathy
Nephropathy

18. UKPDS Blood Pressure Control
blood pressure control reduced risk for
Any diabetes-related endpoint 24% p=0.0046
diabetes-related deaths 32% p=0.019
stroke 44% p=0.013
microvascular disease 37% p=0.0092
heart failure 56% p=0.0043
retinopathy progression 34% p=0.0038
deterioration of vision 47% p=0.0036

19. Diabetes and CHD HOPE Study
9297 pts >55y.o. with DM or vascular disease + 1 CVD risk factor (~3578 DM )
Placebo or Ramipril 10 mg qd followed ~ 4 yrs
Significant reductions in cardiovascular events (MI, stroke and CV death)
Changes seen in both DM and non-DM groups

20. MICRO-HOPE
No clinical proteinuria, CHF or diminished EF and not on ACE.
3577 patients with DM and either known CHD or one additional risk factor.
Ramapril 10 mg/d or placebo.
Study stopped at 4.5 yrs by DSMB

21. ACE Inhibition in DM

22. The Arterial Tree in Diabetes
Conduit Artery Resistance Precapillary Capillaries
Arterioles Arterioles
Atherosclerosis Hypertension Retinopathy Neuropathy
Nephropathy

23. Glucose Control Study Summary
The intensive glucose control policy maintained a lower HbA1c by mean 0.9 % over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk of:
12% for any diabetes related endpoint p=0.029
25% for microvascular endpoints p=0.0099
16% for myocardial infarction p=0.052
24% for cataract extraction p=0.046
21% for retinopathy at twelve years p=0.015
33% for albuminuria at twelve years p=

24. Effect of Improved Glycemic Control
Quality of Life:
Effect of Improved Glycemic Control
P<.001
Improved
P<.01
P<.01
Extended-
release
glipizide
P<.05
Worsened
Quality-of-Life
Analog Rating
Mental
Health
Cognitive
Function
General
Perceived
Health
Symptom
Distress
Testa & Simonson, JAMA, 1998;280;

25. Glucose Control and Costs of Care
A 6 year comparison between patients who improved glucose control (decline in HgbA1C >1%) or not has shown that improved glycemic control reduced annual health care costs for affected individuals
Reductions due to fewer physican and emergency room visits
Cost saving of $ annually.

26. Diabetes a preventable disease
Several trials of diabetes prevention have been conducted for type 1 diabetes using vaccine strategies.
None have yet been successful
For Type 2 diabetes, multiple trials successfully demonstrated that both lifestyle changes and pharmacologic interventions can delay or prevent diabetes among individuals at high risk

27. Prevention of DM 2 F/U DM Incidence Study Control Diet Exercise
Risk
Reduction
Study
Control
Diet
Exercise
Da Qing
6 Yr
68%
44%
31%
DPS
4 Yr
23%
11%
58%
DPP
3 Yr
29%
14%

28. Prevention of Diabetes with Lifestyle Modification

29. Effect of Metformin and Lifestyle Modification on New Onset Diabetes - Lifestyle changes work better as we age
% Decline in Diabetes Incidence
Subject Age

30. Okinawa 161 island archipelago, most live on main island, pop 1.3 m
“Galapagos of the East”
Lowest age-adjusted mortality (CHD, stroke, cancer)
Longest disability-free life expectancy of 47 Japanese prefectures (states)
Highest centenarian prevalence

31. Centenarians in the World (by prevalence)
Willcox DC et al AGE 2006

32. Diabetes – A model for intervention in chronic disease
As the population ages:
Diabetes becomes more common
Diabetes itself is more preventable by a healthy lifestyle
Complications of diabetes while common can be prevented

33. Ushi Okushima 106 Years Young and Still Diggin’ Life
Domo Arigato!
Thank you !