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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
Diagnosis and what is it
Glucose Tolerance Categories
FPG
2-Hour PG on OGTT
Diabetes Mellitus
Diabetes Mellitus
126 mg/dL
100 mg/dL
7.0 mmol/L
Impaired Fasting
Glucose
Normal
5.7 mmol/L
200 mg/dL
140 mg/dL
11.1 mmol/L
Impaired Glucose
Tolerance
7.8 mmol/L
Normal
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197.
What is it ?
Diabetes is a Vascular Disease
% Affected
Background Retinopathy
100 125 150 175 200
Fasting Plasma Glucose
Natural History of Type 2 Diabetes
Post-meal
glucose
350
Gluco 300
250
se
(mg/d 200
150
L)
100
Diabetes
IGT
Fasting
glucose
-15
-10
-5
0
5
10
125
Relative 100
Functio
75
n (%)
50
25
0
15
20
25
Insulin
resistance
ß-cell
-15
-10
-5
0
5
10
Years of Diabetes
Adapted from: International Diabetes Center (Minneapolis,
15
20
25
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, endocrinopathies, drug- or chemicalinduced, and other rare forms
Gestational
Insulin resistance with b-cell
dysfunction
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197.
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 31:596-615, 2008
Diabetes is a Common Disease : Estimated
Prevalence of Diabetes in the US:
Adult Men and Women
Percent of Population
30
Men
Women
21.1
20.2
20
17.8
17.5
12.9 12.4
10
6.8 6.1
1.6 1.7
0
20-39
40-49
Harris, et al. Diabetes Care. 1998;21:518-524, with permission.
50-59
Age (y)
60-74
75+
Estimated Prevalence of Diabetes in the US:
Breakdown by Ethnicity
10
9.3
Diagnosed
Percent of Population
8.2
Undiagnosed
8
6
4.8
4.5
3.6
4
2.5
2
0
Non-Hispanic
White
Data from Harris, et al. Diabetes Care. 1998;21:518-524.
African
American
Hispanic
American
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
1997 Per Capita Health Care Costs:
Persons With and Without Diabetes
25
23.5
Diabetes
Annual Costs ($1000s)
No diabetes
20
15
12.2
10
5
0
2.5
Inpatient
1.5
Outpatient
Services
0.7
0.4
ER
Data from American Diabetes Association. Diabetes Care. 1998;21:296-309.
0.7
0.4
Office
Visits
0.7
0.2
Outpatient
Drugs
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
The Arterial Tree in Diabetes
Conduit Artery Resistance
Arterioles
Atherosclerosis
Hypertension
Precapillary Capillaries
Arterioles
Retinopathy Neuropathy
Nephropathy
Framingham Heart Study 30-Year Follow-Up:
CVD Events in Patients With Diabetes (Ages 35-64)
10
10
9
Men
8
Risk
ratio
Women
11
6
4
30
19
38
9
20
2
6
3*
0
Total
CVD
CHD
Cardiac
failure
Intermittent Stroke
claudication
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.
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;110:1100-1107.
Abbott RD et al. JAMA. 1988;260:3456-3460.
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.
4S: Major CHD Event Reduction in a Patients
With Diabetes
1.00
5.00
0.90
4.00
0.80
Proportion 3.00
32%
without
0.70
major CHD 2.00
event
Diabetic, simvastatin
- P=0.002
0.60
1.00
Diabetic, placebo
0.50
0.00
Nondiabetic, placebo
55%
Nondiabetic, simvastatin
0
1
2
3
- P=0.0001
4
Yr since randomization
Pyörälä K et al. Diabetes Care. 1997;20:614620.
5
6
The Arterial Tree in Diabetes
Conduit Artery Resistance
Arterioles
Atherosclerosis
Hypertension
Precapillary Capillaries
Arterioles
Retinopathy Neuropathy
Nephropathy
UKPDS Blood Pressure Control
blood pressure control reduced risk for
Any diabetes-related endpoint
diabetes-related deaths
stroke
microvascular disease
heart failure
retinopathy progression
deterioration of vision
24%
32%
44%
37%
56%
34%
47%
p=0.0046
p=0.019
p=0.013
p=0.0092
p=0.0043
p=0.0038
p=0.0036
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
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
ACE Inhibition in DM
Hope Trial
Ramipril
Placebo
(n=1808)
(n=1769) P
Combined
277
351
.0004
MI
185
229
.01
Stroke
76
108
.007
CV Death
112
172
.0001
The Arterial Tree in Diabetes
Conduit Artery Resistance
Arterioles
Atherosclerosis
Hypertension
Precapillary Capillaries
Arterioles
Retinopathy Neuropathy
Nephropathy
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%
25%
for any diabetes related endpoint
for microvascular endpoints
16%
24%
for myocardial infarction
for cataract extraction
21%
33%
for retinopathy at twelve years
for albuminuria at twelve years
p=0.029
p=0.0099
p=0.052
p=0.046
p=0.015
p=0.000054
Quality of Life:
Effect of Improved Glycemic Control
0.4
P<.001
Improved
0.3
P<.01
P<.01
P<.05
0.2
0.1
0
-0.1
-0.2
Worsened
-0.3 Quality-of-Life Mental
Analog Rating Health
Cognitive
Function
Testa & Simonson, JAMA, 1998;280;1490-1496.
General
Perceived
Health
Symptom
Distress
Placebo
Extendedrelease
glipizide
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 $600-1000 annually.
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
Prevention of DM 2
F/U
DM
Incidence Risk
Reduction
Study
Control
Da Qing
6 Yr
68%
Diet
Exercise
44%
DPS
4 Yr
23%
11%
58%
DPP
3 Yr
29%
14%
58%
31%
Prevention of Diabetes with Lifestyle Modification
Effect of Metformin and Lifestyle Modification on New Onset
Diabetes - Lifestyle changes work better as we age
% Decline in Diabetes Incidence
80
70
60
50
Metformin
Lifestyle
40
30
20
10
0
25-44
44-59
Subject Age
>59
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
Centenarians in the World (by prevalence)
Willcox DC et al AGE 2006
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
Ushi Okushima 106 Years Young and
Still Diggin’ Life
Domo
Arigato!
Thank you !