Transcript Prediabetes - Gonzaga University

Prediabetes
Carol H. Wysham, MD
What is Diabetes?
• Normally, blood sugar (glucose) levels are kept in
the normal range by the release of insulin from the
islet cells of the pancreas
• Insulin helps glucose enter the cells.
• Diabetes occurs when the body doesn’t produce
enough insulin or the body can’t use it properly.
This results in sugar (glucose) building up within
the bloodstream
• Diagnosed by blood test
– Fasting glucose > 125mg/dl
– Random blood glucose > 200mg/dl
Diabetes
Body lacks insulin or is
unable to use insulin
effectively
Pancreas
Muscle and
Fat Cells
Cannot Produce Enough
Insulin
Cannot Use Insulin
Effectively
How Food is Digested
1. Food enters
stomach
4. Pancreas
releases insulin
5. Insulin unlocks
receptors
6. Glucose enters
cell
3. Glucose enters
bloodstream
2. Food is converted
into glucose
What Causes Diabetes
• Type 1 Diabetes is caused by an activation of the
immune system that causes destruction of the
insulin producing cells (islet cells) in the pancreas.
• Type 2 Diabetes is caused by two conditions:
– Insulin resistance: an inherited problem where the
body needs more insulin to process sugar. Insulin
resistance worsens with increased weight.
– Insulin deficiency: the islet cells of the pancreas
are unable to make enough insulin to overcome the
resistance.
Diabetes: 17 Million and Climbing
• Estimated 11 million diagnosed + 5.4 million undiagnosed
• Type 2 diabetes accounts for 95% of cases
• Over 2,200 new cases are diagnosed each day
•+60%
(Millions)
•Diagnosed Cases
12
•+17%
8
4
0
1980
1990
•From Centers for Disease Control and Prevention, 2000.
2000 (Estimated)
Residual Lifetime Risk of Diabetes (%)
Baseline Age, y
0
10
20
30
40
50
60
70
Male
32.8
32.1
31.9
31.3
29.5
25.5
18.9
11.2
Narayan KMV et al JAMA 290: 1884, 2003
Female
38.5
37.9
37.3
35.7
32.6
28.2
22.4
14.6
NHANES: Diabetes Prevalence by Age
14
12
1990
10
1998
8
6
4
2
0
18-29
30-39
40-49
50-59
Age, in years
Source: CDC
60-69
>79
The Prevalence of Diabetes
and Obesity
Diabetes
Mean body weight
$ spent on fast food
7.0
78 (110)
65% of US adults are overweight
77
6.5
76
6.0
75
kg
Prevalence (%)
7.5
Prevalence of obesity, increased
by 61% since 1991
5.5
74
5.0
4.5
73
4.0
1990
72(70)
1992
1994
Year
1996
1998
2000
BMI and weight gain
major risk factors
for diabetes
The Less You Exercise and the More You Watch TV,
the Chances of Getting Diabetes Will Be
Significantly Increased!
3.0
2.5
RR
2.0
1.5
1.0
<10.0
0.5
10.0-23.5
0
23.6-45.9
>15.0
8.1-15.0
Quartiles of no. of hours
watching TV per week
3.6-8.0
Hu et al. Arch Intern Med. 2001;161:1542.
3.5
46.0
Quartiles of
MET - hours per week
The Evolution of Man:
The Thrifty Gene Hypothesis
Not too long ago we were
hunters and gatherers doing
physical labor for our daily
existence
Why is Diabetes More Common?
+
+
=
You would not believe the
increase in diabetes in
Japan and other developed
countries around the world
Risk Factors for the Development of
Type 2 Diabetes
• Family history of
diabetes
• Obesity
– Especially central
• Hypertension
• High triglycerides
• Low HDL-C
• Elevated glucose
• Ethnicity other than
•
•
•
•
•
Caucasian
Vascular disease
History of gestational
diabetes
History of baby
weighing > 9 lbs
Sedentary lifestyle
Schizophrenia
Patterns of Body Fat Distribution
Abdominal
(android)
Lower body
(gynoid)
Acanthosis Nigricans
Why Do We Worry About Diabetes?
• Association with debilitating complications
– Preventable with aggressive treatment
• High cost of care
– Mostly due to costs of caring for
complications
• Diabetes can be prevented
Complications of Diabetes
End-Stage Kidney
Disease: 17x
Stroke: 2-6x
Retinopathy: 25x
Foot/Leg
Amputations:
5x
Heart Disease: 2-4x
United Kingdom Prospective Diabetes
Study (UKPDS)
Change
in HbA1C
Microvascular
Complications
0
0
-1
-5
-2
- 0.9%
- 25%
-10
-3
-15
-4
-20
-5
-25
1% Decrease in HbA1c = 25% Decrease in Microvascular Risk!
Glucose Metabolism
Normal Glucose
Metabolism
Prediabetes
Diabetes
Glucose Levels in Normal,
Prediabetic and Diabetic Subjects
Plasma glucose (mg/dl)
220
200
180
Diabetes
160
IGT
140
120
Normoglycaemia
100
0
1
2
3
Time following meal (hrs)
Harris MI. Diabetes Care 1993, 16: 642-652.
What is Prediabetes?
Prevalence of Prediabetes in US Adults
aged 45 - 74
All races
22.6% (11.9 million)
Non-Hispanic Whites
22.2% (8.9)
Non-Hispanic Blacks
18.9% (1.0)
Mexican-Americans
27.3% (0.7)
Why Worry About Prediabetes?
• Predicts high risk for development of
diabetes
• Predicts high risk for development of
atherosclerotic vascular disease
• Both are largely preventable through lifestyle
and pharmacologic interventions
Risk of Cardiovascular Disease Is
Elevated Prior to Diagnosis of T2DM
30.00
% with CVD
25.00
27
20.00
15.00
18
12.00
10.00
5.00
6.00
0.00
Normal
IGT
*MI=myocardial infarction.
Adapted from: Hu F, et al. Diabetes Care. 2002;25:1129-1134.
New DM
Previous DM
Prevention of Diabetes
The Finnish Diabetes Prevention Study:
Lifestyle Modifications (cont’d)
Incidence of diabetes
(cases/1000 person-years)
Control (n=250)
Diet intervention (n=256)
80
60
40
20
0
Tuomilehto et al. N Engl J Med. 2001;344:1343.
 58%
The Finnish Diabetes Prevention Study:
Lifestyle Modifications
• 522 overweight individuals with IGT randomized to
– Control: diet instruction at the onset of study
– Individualized advice given 7 times in the first year and
every 3 months thereafter with goals of
• Weight loss 5%
• Reducing fat intake to <30% of energy consumption
• Increasing fiber intake to 15 g/1000 kcal
• Exercising at a moderate level for 30 min/d
• Primary end point: Prevention of diabetes, as assessed
by annual OGTT
Tuomilehto et al. N Engl J Med. 2001;344:1343.
The Finnish Diabetes Prevention Study:
Lifestyle Modifications (cont’d)
Control (n=250)
Weight (kg)
Diet intervention (n=256)
Waist (cm)
SBP (mm Hg) DBP (mm Hg)
Change from baseline
0
-1
-2
-3
-4
-5
-6
P<0.001
Tuomilehto et al. N Engl J Med. 2001;344:1343.
P<0.001
P=0.007
P=0.02
FDPS: Incidence of Diabetes By Success
Score
40
35
Control
Intervention
30
25
20
15
10
5
0
0
1
2
3
Success Score
4
5
The Diabetes Prevention Program
A Randomized Clinical Trial
to Prevent Type 2 Diabetes
in Persons at High Risk
Sponsored by the NIDDK, NIA, NICHD, NIH, IHS, CDC, ADA,
and other agencies and corporations
Diabetes Prevention Program:
Primary Objectives
• Compare safety and efficacy of 4 interventions for
preventing or delaying development of diabetes
– Standard lifestyle recommendations + masked
metformin titrated to 850 mg bid or troglitazone
400 mg/d
– Standard lifestyle recommendations + masked
placebo
– Intensive lifestyle intervention by case managers
with goals of
–7% weight reduction through healthy eating and
physical activity
–150 min/wk moderate intensity physical activity
The Diabetes Prevention Program Research Group. Diabetes Care. 1999;22:623.
Diabetes Prevention Program:
Achievement of Study Goals
Average follow-up of 2.8 years
Goal
Lifestyle modifications
Weight loss
Physical activity
(min/wk)
7%
150
Pharmacologic intervention
Compliance
80%
Full dose
2 tablets/d
% Achieving Goal
Week 24
50%
74%
Last visit
38%
58%
Placebo
77%
97%
Metformin
72%
84%
The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.
Diabetes Prevention Program:
Effects on Weight and Dietary Intake
Lifestyle
Placebo Metformin Intervention P Value
Change in weight (kg)
-0.1
-2.1
-5.6
<0.001
Change in fat intake*
(% of total calories)
-0.8
-0.8
-6.6
<0.001
Change in energy intake
(kcal/d) at 1 year
-249
-296
-450
<0.001
*Baseline fat intake was 34.1% of total calories.
The goal of intensive lifestyle modification was <25% of total calories.
The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.
Diabetes Prevention Program:
Progression to Type 2 Diabetes
Cases/100 person-years
Average follow-up of 2.8 years
12
10
 31%*
8
 58%*
6
4
2
0
Placebo
Metformin
*All pairwise comparisons significantly different by group; sequential log-rank test.
The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.
Intensive
lifestyle
Diabetes
Body lacks insulin or is
unable to use insulin
effectively
Pancreas
Muscle and
Fat Cells
Cannot Produce Enough
Insulin
Cannot Use Insulin
Effectively
Prevalence of IR in Selected
Metabolic Disorders
Hypertriglyceridemia: 84%
T2DM: 92%
Low HDL cholesterol: 88%
Hyperuricemia: 63%
IR
Hypertension: 58%
Those with multiple disorders
(diabetes, hypertension, dyslipidemia, and hyperuricemia):
95%
Bonora E, et al. Diabetes. 1998;47:1643-1649.
Haffner SM, et al. Am J Med. 1997;103:152-162.
Who Is Insulin Resistant?
• 30% of the U.S.
population, age 40–74
years
• 60% of all patients
with CVD
• 50% of patients with
confirmed coronary heart
disease (CHD) and no prior
history of diabetes
• 92% of patients with T2DM
Harris M, et al. Diabetes Care. 1998;21(4):518-524.
Haffner SM, et al. Circulation. 2000;101:975-980.
Kowalska I, et al. Diabetes Care. 2001;24(5):897-901.
Haffner SM, et al. Am J Med. 1997;103:152-162.
How to Detect Insulin Resistance
Those with any of the
manifestations of the
metabolic syndrome:
– Increased waist
circumference
– Hypertension
– Hypertriglyceridemia
– Low HDL-C
– Atherosclerosis
– Impaired glucose
tolerance
Interrelation Between Atherosclerosis
and Insulin Resistance
Hypertension
Obesity
Hyperinsulinemia
Insulin
Resistance
Diabetes
Dyslipidemia
Small, dense LDL
Inflammation
Hypercoagulability
Atherosclerosis
Biological Functions of the Adipocyte
Inert Storage Depot
Fatty Acids
Secretory/Endocrine Gland
Glucose
Fed
Leptin
ANS
Fasted
Fatty Acids
Glycerol
Kahn B, Flier J. J Clin Invest. 106:473 2000
Leptin, FFA,
TNF, IL-6,
Adiponectin,
Resistin,
Angiotensinogen
PAI-1, Other
Steps in the Development of Diabetes
Defect in mitochondrial fat oxidation
Excess energy intake
Increase fat in fat cell, muscle and liver
Insulin Resistance
Release of FFA and inflammatory markers from fat cell
Death of islet cell
Diabetes Mellitus
Screening for Diabetes and Prediabetes
Screen every adult > 40 years of age
< 100
Normal
100 - 125
Prediabetes
> 125
Diabetes
What Can You Do to Prevent Diabetes?
• If over 40, get screened with a fasting
glucose level.
• If high risk or if glucose levels are over 100
mg/dl, start making lifestyle changes to
improve diet and exercise.
• Talk with your health care provider about
other cardiovascular risk factors
Health
Physical Activity
+
Sound Nutrition
Good Health
Health
The first part of our
equation is activity
Get moving, find something you
enjoy
Physical Activity Pyramid
Prescription pad
Prescription pad
Activities Log
Week #
Mon
Activity
# of Minutes
Tue
Wed
Thu
Fri
Sat
Sun
Participant’s signature:
Date:
Health
The second part of the
equation is nutrition
Your body needs the right fuel to help it
work well.
23 subjects with vascular disease were treated with diet low in starch
and high in saturated fat. After 6 weeks, subjects lost 5% of body
weight. Lipids were slightly improved, but homocysteine and CRP
both increased
Food Pyramid
Management of Obesity: Treatment
Options
Modality
Recommendation
Reduced-calorie diet
Reduce energy intake by 500 to 1,000 kcal/day to achieve a weight
loss of 1 to 2 lbs/week over a 6-month period
Increased activity
Start with 30 to 45 minutes moderate activity 3 to 5 days/week, and
work up to at least 30 minutes moderate-intensity physical activity
on most or all days/week
Behavior modification
Use multiple behavioral strategies (eg, self-monitoring of eating
habits and physical activity)
Pharmacotherapy
Recommend appropriate pharmacotherapy* for patients with BMI 
30 kg/m2, or with BMI  27 kg/m2 with one or more comorbid
conditions
Surgery
Consider for patients with class 3 obesity, or class 2 obesity with
comorbid conditions, for whom other treatments have failed
*In combination with diet, increased activity, and behavior modification.
(NIH. Obes Res. 1998)
Gastric Bypass Surgery for Obesity
Improvements in technique and
“advertising” has resulted in a
resurgence of interest in bariatric
surgery for treatment of obesity
1990 – 16,000/year
2003 – 200,000/year
Healthy Lifestyle Improves
All Cardiovascular Risk
Factors:
Glucose
BP
Cholesterol
30-60 minutes/day
Restrict:
Calories
Salt
Simple carbohydrates
Animal Fats
High fiber, low fat diet – 3 meals/day
For Effective Weight Loss
• 30 – 60 minutes of exercise most days of the
week
– Mixture of cardiovascular and weight training
• Cut calories by about 30%
• Do not restrict any one category too severely
• Have realistic expectations – unusual for
people to be able to maintain > 20% weight
loss for the long-term.
How Can You Help Reduce Your Risk of Diabetes?
Limit alcohol to
1-2 drinks
per day.
Take your
medications
regularly.
What are goals to healthy living?
Be SMART
Specific
Measurable
Achievable
Relevant
Time
www.aace.com
www.diabetes.org
www.powerofprevention.com
www.fitness.gov
www.presidentschallenge.org