TYPE 2 DIABETES MELLITUS:
NEW HOPE FOR PREVENTION
Robert Dobbins, M.D. Ph.D.
Learning Objectives
Recognize current trends in the
prevalence of type 2 diabetes.
Q Learn differences between type 1
and type 2 diabetes.
Q List risk factors for type 2 diabetes.
Q Understand how type 2 diabetes can
be prevented or delayed.
Q Introduce the concept of prediabetes.
Q
Definition
Diabetes mellitus: A chronic
disorder characterized by a
deficiency of insulin secretion
and/or insulin effect, which causes
hyperglycemia, disturbances of
carbohydrate, fat and protein
metabolism, and a constellation of
chronic complications .
Diagnostic Criteria
Normal
Fasting
Glucose
Random
OGTT
(2 hr)
<110 mg/dl
(5.5 mM)
<140 mg/dl
(7.7 mM)
IFG/IGT
111-125 mg/dl
140-200 mg/dl
Diabetes
>126 mg/dl
(7.0 mM)
>200 mg/dl
(11.1 mM)
>200 mg/dl
(11.1 mM)
*Confirmation on a second day by any of the above methods
Two Flavors of Diabetes
Type 1
Type 2
Features of Type 1
Diabetes
80% occur before age 20
Q May occur at any age
Q Insulin deficient
Q
– autoimmune pathogenesis, HLA linked
– less commonly non-immune mediated
Ketosis prone
Q Normal insulin sensitivity
Q
Features of Type 2
Diabetes
Most common after age 40
Q Abdominal obesity present in 90%
Q Insulin resistance/hyperinsulinemia
Q Ketosis resistant
Q Hypertension common
Q High VLDL, low HDL cholesterol
Q Accelerated atherosclerosis
Q High in risk in many ethnic groups
Q
Prevalence of Diagnosed
Diabetes Mellitus
20
15
Patients
with
10
Diabetes
(millions)
5
0
1960
1970
1980
1990
2000
DM
10.2 million
Undiagnosed
5.4 million
IGT / Pre-Diabetes
13.4 million
At-Risk
40 million
Harris et al., Diabetes Care, 1998
Risk Factors for Type 2
Diabetes
Age > 40
Q Family history of diabetes
Q Ethnicity
Q Obesity; abdominal fat distribution
Q GDM, or infant > 9 lbs
Q Hypertension, hyperlipidemia
Q Previous Impaired Glucose
Tolerance
Q
Body Mass Index
Height
Weight
5'0"
5'1"
5'2"
5'3"
5'4"
5'5"
5'6"
5'7"
5'8"
5'9"
5'10"
5'11"
6'0"
6'1"
6'2"
6'3"
6'4"
100
20
19
18
18
17
17
16
16
15
15
14
14
14
13
13
12
12
105
21
20
19
19
18
17
17
16
16
16
15
15
14
14
13
13
13
110
21
21
20
19
19
18
18
17
17
16
16
15
15
15
14
14
13
115
22
22
21
20
20
19
19
18
17
17
17
16
16
15
15
14
14
120
23
23
22
21
21
20
19
19
18
18
17
17
16
16
15
15
15
125
24
24
23
22
21
21
20
20
19
18
18
17
17
16
16
16
15
130
25
25
24
23
22
22
21
20
20
19
19
18
18
17
17
16
16
135
26
26
25
24
23
22
22
21
21
20
19
19
18
18
17
17
16
140
27
26
26
25
24
23
23
22
21
21
20
20
19
18
18
17
17
145
28
27
27
26
25
24
23
23
22
21
21
20
20
19
19
18
18
150
29
28
27
27
26
25
24
23
23
22
22
21
20
20
19
19
18
155
30
29
28
27
27
26
25
24
24
23
22
22
21
20
20
19
19
160
31
30
29
28
27
27
26
25
24
24
23
22
22
21
21
20
19
165
32
31
30
29
28
27
27
26
25
24
24
23
23
22
21
21
20
170
33
32
31
30
29
28
27
27
26
25
24
24
23
22
22
21
21
175
34
33
32
31
30
29
28
27
27
26
25
24
24
23
22
22
21
180
35
34
33
32
31
30
29
28
27
27
26
25
24
24
23
22
22
185
36
35
34
33
32
31
30
29
28
27
27
26
25
24
24
23
23
190
37
36
35
34
33
32
31
30
29
28
27
26
26
25
24
24
23
195
38
37
36
35
33
32
31
31
30
29
28
27
26
26
25
24
24
200
39
38
37
35
34
33
32
31
30
30
29
28
27
26
26
25
24
205
40
39
37
36
35
34
33
32
31
30
29
29
28
27
26
26
25
210
41
40
38
37
36
35
34
33
32
31
30
29
29
28
27
26
26
215
42
41
39
38
37
36
35
34
33
32
31
30
29
28
28
27
26
220
43
42
40
39
38
37
36
34
33
32
32
31
30
29
28
27
27
225
44
43
41
40
39
37
36
35
34
33
32
31
31
30
29
28
27
230
45
43
42
41
39
38
37
36
35
34
33
32
31
30
30
29
28
235
46
44
43
42
40
39
38
37
36
35
34
33
32
31
30
29
29
240
47
45
44
43
41
40
39
38
36
35
34
33
33
32
31
30
29
245
48
46
45
43
42
41
40
38
37
36
35
34
34
32
31
31
30
250
49
47
46
44
43
42
40
39
38
37
36
35
34
33
32
31
30
Correlation BMI and Fat Mass
Prevalence of Type 2 DM
by Body Mass Index
35
30
25
% with 20
Type 2 DM 15
10
5
0
<25 25- 30- >35
<25 25- 30- >35
30 35
30 35
BMI
Age 20-54
Age 55-74
Increasing Prevalence of
Obesity in the United States
Mokdad et al., JAMA, 2001
Increasing Prevalence of Type
2 DM in the United States
5.1% = 10.2 million people
7.3% = 15 million people
Mokdad et al., JAMA, 2001
Risk Factors for Type 2
Diabetes
30
25
20
Percent of
Nondiabetic 15
Individuals
10
5
0
None
1
2
3
Number of Risk Factors
4+
Microvascular
Complications
Q
Diabetic retinopathy
background retinopathy
Q macular edema
Q proliferative retinopathy
Q
Diabetic nephropathy
Q Diabetic neuropathy
Q
distal symmetrical polyneuropathy
Q mononeuropathy (peripheral, cranial nerves)
Q autonomic neuropathy
Q
Diabetic Retinopathy
Macrovascular
Complications
Complications
Q
Q
Q
Coronary Heart
Disease
Cerebrovascular
Disease
Peripheral
Vascular Disease
Risk Factors
Q
Q
Q
Q
Q
Dyslipidemia
Hypertension
Smoking
Family history
Hyperglycemia
Complications of Diabetes
Magnitude of the Problem
Diabetic retinopathy: most
common cause of blindness before
age 65
Q Nephropathy: most common cause
of ESRD
Q Neuropathy: most common cause
of non-traumatic amputations
Q 2-3 fold increase in cardiovascular
disease
Q
Mortality Due to Diabetes
Mellitus is Steadily Increasing
Prevention of Diabetic
Complications
Weight reduction
Q Exercise
Q Control glycemia
Q Improve lipid profile
Q Smoking cessation
Q Treat Hypertension
Q Daily aspirin therapy
Q
Any Diabetes Related Endpoint (cumulative )
1401 of 3867 patients (36%)
% of patients with an event
60%
Conventional (1138)
Intensive (2729)
p=0.029
40%
20%
Risk reduction 12%
(95% CI: 1% to 21%
0%
0
3
6
9
12
Years from randomisation
15
ukpds
Any Diabetes Related Endpoint (cumulative )
1401 of 3867 patients (36%)
% of patients with an event
60%
Conventional (1138)
Intensive (2729)
p=0.029
40%
20%
Diabetes Treatment
Diabetes
Prevention
Risk
reduction
12%
(95% CI: 1% to 21%
0%
0
3
6
9
12
Years from randomisation
15
ukpds
Prevention is the Key
Come and get it!
Exercise
Every Little Bit Helps
Prevention of Type 2 Diabetes
Finnish Diabetes Prevention Study Group
Q
Q
Q
Q
Q
Q
522 subjects
2:1 female:male ratio
Age - 40-65 years
Weight - BMI > 25
Impaired glucose tolerance with plasma
glucose of 140-200 mg/dl 2h after
ingesting 75 gm of oral glucose
Exclusions - diabetes, chronic illness,
psychological or physical disabilities
Tuomilehto et al., NEJM, 2001
Design of Interventions
Finnish Diabetes Prevention Study Group
Q
Q
Randomized to two study groups
Control Group
– 2-page leaflet on diet and exercise
– nutritionist reviewed a 3-day food diary
Q
Intervention Group
–
–
–
–
individualized, detailed diet/exercise advice
nutrition appointments every 2-3 months
3-day food diary completed every 3 months
Supervised, progressive, individuallytailored physical training sessions
Tuomilehto et al., NEJM, 2001
Success Achieving Treatment Goals
Finnish Diabetes Prevention Study Group
Goal of Intervention
Weight Reduction
(>5% of body weight)
Fat Intake
(<30% of energy intake)
Saturated Fat Intake
(<10% of energy intake)
Fiber Intake
>15 g / 1000 kcal
Exercise
>4 hours / week
Intervention
Group
Control
Group
% of subjects
43
13
47
26
26
11
25
12
86
71
Tuomilehto et al., NEJM, 2001
Prevention of Type 2 Diabetes
Cumulative Probability of
Progressing to Diabetes
Finnish Diabetes Prevention Study Group
0.5
0.4
Control Group
0.3
0.2
0.1
Intervention Group
0
0
1
2
3
4
5
6
Study Year
Tuomilehto et al., NEJM, 2001
Prevention of Type 2 Diabetes
Cumulative Probability
of Progressing to
Diabetes
Finnish Diabetes Prevention Study Group
0.4
0.3
0.2
0.1
0
None
1
2
3
4+
Intervention Goals Achieved
Tuomilehto et al., NEJM, 2001
Prevention of Type 2 Diabetes
Diabetes Prevention Program Research Group
Q
Q
Q
Q
Q
Q
3234 subjects
2:1 female:male ratio
Age - >25 years
Weight - BMI > 24
Impaired glucose tolerance on an OGTT
or impaired fasting glucose
Exclusions - diabetes, chronic illness,
taking medications altering insulin
sensitivity
DPPRG, NEJM, 2002
Design of Interventions
Diabetes Prevention Program Research Group
Q
Q
Randomized to three study groups
Control Group
– standard lifestyle recommendations with an
annual dietitian visit and placebo medication
Q
Drug Treatment Group
– standard lifestyle recommendations
– Metformin or Rosiglitazone
Q
Intensive Lifestyle Modification Group
– diet/exercise/behavior modification curriculum
– monthly case-manager visits and group sessions
DPPRG, NEJM, 2002
Success Achieving Treatment Goals
Diabetes Prevention Program Research Group
DPPRG, NEJM, 2002
Prevention of Type 2 Diabetes
Diabetes Prevention Program Research Group
DPPRG, NEJM, 2002
Prevention of Type 2 Diabetes
Summation of Clinical Trials
Q
Goals
– Lose weight - 10-20 pounds is enough
– increase activity to walking 30 min/day or
going to a gym 3 days/week
Q
Results
– One case of diabetes is prevented for every
7-8 people who participate in an intensive
lifestyle intervention program for 3 years
– Achieving all diet and exercise goals
virtually stalls the progression to diabetes
Definition
Pre-diabetes: A serious, treatable
medical condition in which blood
glucose levels are higher than
normal but not yet high enough to
be diagnosed as diabetes. Without
intervention, nearly one-half of
these individuals progress to
clinical diabetes in five years.
For info see http://www.diabetes.org/main/info/pre-diabetes.jsp
Type 2 Diabetes Screening Program
Conditions that must be met
Q
Q
Q
Q
Q
Q
Q
Disease represents a significant burden
Natural history of the disease is understood
The disease can be recognized at a preclinical
(asymptomatic) stage
Sensitive and specific screening tests are
available
Early detection and treatment improve
outcomes
Testing and treatment are cost-effective
Systematic procedures can be adopted
Socioeconomic Costs of
Diabetes Mellitus
Diabetes costs the U.S. economy
$105 billion annually
Q One out of every ten U.S.
healthcare dollars is spent for
diabetes
Q One of four Medicare dollars pays
for care in individuals suffering
from diabetes
Q
Actual Therapy
Intensive Policy
aim for < 6 mmol/L
Conventional Policy
accept < 15 mmol/L
proportion of patients
100
diet alone
additional non-intensive
pharmacological therapy
80
60
intensive
pharmacological
therapy
40
diet alone
20
0
1
2
3
4
5
6
7
8
9 10 11 12
1
2
3
4
5
Years from randomisation
6
7
8
9 10 11 12
Pathophysiology-based
Therapy for Type 2 Diabetes
Q
Defect in insulin sensitivity
– exercise
– weight reduction
– thiazolidinediones
– metformin
Q
Defect in insulin secretion
– sulfonylureas (mild defect)
– insulin (severe defect)
Pathophysiology-based
Therapy for Type 2 Diabetes
Q
Increased hepatic glucose output
– metformin > thiazolidinediiones
– insulin (sulfonylurea)
Q
Carbohydrate absorption (postprandial hyperglycemia)
– acarbose
Prevention of Diabetic
Complications
Optimize glycemic control
Q Control hypertension < 135/85
mm Hg
Q Screen at diagnosis, then annually
for microalbuminuria
Q Use angiotensin convertingenzyme inhibitor when
microalbuminuria is reproducible
Q
Prevention of Diabetic
Complications
Ophthalmoscopic exam of the eye
every 3-6 months with a formal
exam annually
Q Determine the fasting lipid profile
each year and treat to LDL <100
Q Prescribe 325 mg aspirin to be
taken daily
Q
Diagnostic Criteria for
Diabetes
Symptoms of diabetes +
casual glucose > 200 mg/dl (11.1
mmol/l)
Q FPG > 126 mg/dl (7.0 mmol/l)
Q 2h PG > 200 mg/dl (11.1 mmol/l)
during OGTT
*Confirmation on a second day by
any of the above methods
Q