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
H o p e T ria l
R a m ip ril
P la ceb o
(n = 1 8 0 8 )
(n = 1 7 6 9 )
P
C o m b in ed
277
351
.0 0 0 4
MI
185
229
.0 1
S tro k e
76
108
.0 0 7
C V D ea th
112
172
.0 0 0 1
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 !