Prediabetes

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Prediabetes

• Carol H. Wysham, MD

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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 doesnt produce
  enough insulin or the body cant use it properly.
  This results in sugar (glucose) building up
  within the bloodstream
• Diagnosed by blood test
• Fasting glucose gt 125mg/dl
• Random blood glucose gt 200mg/dl

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Diabetes

• Body lacks insulin or is unable to use insulin
  effectively

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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.

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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

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• 17

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• Diagnosed Cases (Millions)

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0
1980
1990
2000 (Estimated)

• From Centers for Disease Control and Prevention,
  2000.

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Residual Lifetime Risk of Diabetes ()
Baseline Age, y Male Female
0 32.8 38.5
10 32.1 37.9
20 31.9 37.3
30 31.3 35.7
40 29.5 32.6
50 25.5 28.2
60 18.9 22.4
70 11.2 14.6
80 5.2 6.9
Narayan KMV et al JAMA 290 1884, 2003
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NHANES Diabetes Prevalence by Age

Age, in years
Source CDC
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The Prevalence of Diabetes and Obesity
Prevalence of obesity, increased by 61 since
1991 65 of US adults are overweight BMI and
weight gain major risk factors for diabetes
(110)
Prevalence ()
kg
(70)
Year
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The Less You Exercise and the More You Watch TV,
the Chances of Getting Diabetes Will Be
Significantly Increased!
3.0
2.5
2.0
RR
1.5
1.0
lt10.0
0.5
10.0-23.5
0
23.6-45.9
gt15.0
Quartiles ofMET - hours per week
8.1-15.0
?46.0
3.6-8.0
Quartiles of no. of hourswatching TV per week
?3.5
Hu et al. Arch Intern Med. 20011611542.
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The Evolution of Man The Thrifty Gene Hypothesis
Not too long ago we were hunters and gatherers
doing physical labor for our daily existence
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Why is Diabetes More Common?



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You would not believe the increase in diabetes in
Japan and other developed countries around the
world
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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 gt 9 lbs
• Sedentary lifestyle
• Schizophrenia

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Type 1 and Type 2 DiabetesHeredity

• 4-8 in offspring

• 30-50 in offspring

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Patterns of Body Fat Distribution
Lower body
Abdominal
(gynoid)
(android)
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Acanthosis Nigricans
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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

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Complications of Diabetes
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United Kingdom Prospective Diabetes Study (UKPDS)
Microvascular Complications
Change in HbA1C
0 -1 -2 -3 -4 -5
0 - 5 -10 -15 -20 -25
- 0.9
Change in Rate of Complications
- 25
Change in HbA1c
1 Decrease in HbA1c 25 Decrease in
Microvascular Risk!
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Glucose Metabolism
Normal Glucose Metabolism
Diabetes
Prediabetes
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Glucose Levels in Normal, Prediabetic and
Diabetic Subjects
220
200
180
160
Plasma glucose (mg/dl)
140
120
100
0
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What is Prediabetes?
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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)
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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

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Risk of Cardiovascular Disease Is Elevated Prior
to Diagnosis of T2DM
with CVD
MImyocardial infarction. Adapted from Hu F, et
al. Diabetes Care. 2002251129-1134.
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Prevention of Diabetes
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The Finnish Diabetes Prevention Study Lifestyle
Modifications (contd)
? 58
Incidence of diabetes (cases/1000 person-years)
Tuomilehto et al. N Engl J Med. 20013441343.
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The Finnish Diabetes Prevention StudyLifestyle
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 lt30 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. 20013441343.
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The Finnish Diabetes Prevention Study Lifestyle
Modifications (contd)
Change from baseline
Plt0.001
Plt0.001
P0.007
P0.02
Tuomilehto et al. N Engl J Med. 20013441343.
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FDPS Incidence of Diabetes By Success Score
Incidence of Diabetes ()
Success Score
Tuomilehto et al. NEJM2001 344 1343
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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
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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. 199922623.
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Diabetes Prevention ProgramAchievement of Study
Goals

• Average follow-up of 2.8 years
• Goal Achieving Goal
• Lifestyle modifications Week 24 Last visit
• Weight loss ?7 50 38
• Physical activity ?150 74 58
• (min/wk)
• Pharmacologic intervention Placebo Metformin
• Compliance ?80 77 72
• Full dose 2 tablets/d 97 84

The Diabetes Prevention Program Research Group. N
Engl J Med. 2002346393.
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Diabetes Prevention ProgramEffects on Weight
and Dietary Intake

• Lifestyle Placebo Metformin
  Intervention P Value
• Change in weight (kg) -0.1 -2.1 -5.6
  lt0.001
• Change in fat intake
• ( of total calories) -0.8 -0.8 -6.6
  lt0.001
• Change in energy intake
• (kcal/d) at 1 year -249 -296 -450
  lt0.001

Baseline fat intake was 34.1 of total calories.
The goal of intensive lifestyle modification
was lt25 of total calories.
The Diabetes Prevention Program Research Group. N
Engl J Med. 2002346393.
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Diabetes Prevention ProgramProgression to Type
2 Diabetes
Average follow-up of 2.8 years
? 31
Cases/100 person-years
? 58
Placebo
Metformin
Intensive lifestyle
All pairwise comparisons significantly different
by group sequential log-rank test.
The Diabetes Prevention Program Research Group. N
Engl J Med. 2002346393.
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Diabetes

• Body lacks insulin or is unable to use insulin
  effectively

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Prevalence of IR in Selected Metabolic Disorders
Hypertriglyceridemia 84
Hyperuricemia 63
IR
T2DM 92
Hypertension 58
Low HDL cholesterol 88
Those with multiple disorders (diabetes,
hypertension, dyslipidemia, and
hyperuricemia) 95
Bonora E, et al. Diabetes. 1998471643-1649. Haff
ner SM, et al. Am J Med. 1997103152-162.
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Who Is Insulin Resistant?

• 30 of the U.S. population, age 4074 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.
199821(4)518-524. Haffner SM, et al.
Circulation. 2000101975-980. Kowalska I, et al.
Diabetes Care. 200124(5)897-901. Haffner SM, et
al. Am J Med. 1997103152-162.
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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

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Interrelation Between Atherosclerosis and Insulin
Resistance
Hypertension Obesity Hyperinsulinemia Diabetes Dys
lipidemia Small, dense LDL Inflammation Hypercoagu
lability
InsulinResistance
Atherosclerosis
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Biological Functions of the Adipocyte
Secretory/Endocrine Gland
Inert Storage Depot
Fatty Acids
Glucose
Leptin
Fed
Leptin, FFA, TNF, IL-6, Adiponectin, Resistin,
Angiotensinogen PAI-1, Other
ANS
Fasted
Fatty Acids
Glycerol
Insulin
Kahn B, Flier J. J Clin Invest. 106473 2000
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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
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Screening for Diabetes and Prediabetes
Screen every adult gt 40 years of age
lt 100
gt 125
100 - 125
Diabetes
Normal
Prediabetes
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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

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Health

• Physical Activity

Sound Nutrition
Good Health
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Health

• The first part of our equation is activity
• Get moving, find something you enjoy

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Physical Activity Pyramid
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Prescription pad
Prescription pad
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Activities Log
Week Activity of Minutes
Mon
Tue
Wed
Thu
Fri
Sat
Sun
Participants signature Participants signature Date
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Health

• The second part of the equation is nutrition
• Your body needs the right fuel to help it work
  well.

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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
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Food Pyramid
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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 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 Use
multiple behavioral strategies (eg,
self-monitoring of eating habits and physical
activity) Recommend appropriate pharmacotherapy
for patients with BMI ? 30 kg/m2, or with BMI ?
27 kg/m2 with one or more comorbid
conditions Consider for patients with class 3
obesity, or class 2 obesity with comorbid
conditions, for whom other treatments have failed
Increased activity
Behavior modification
Pharmacotherapy
Surgery
In combination with diet, increased activity,
and behavior modification.
(NIH. Obes Res. 1998)
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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
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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
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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 gt 20 weight loss for the
  long-term.

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How Can You Help Reduce Your Risk of Diabetes?
Take your medications regularly.
If overweight, lose weight.
Limit alcohol to 1-2 drinks per day.
? Physical activity
Eat foods low in fat calories.
Stop smoking!
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What are goals to healthy living? Be SMART

• Specific
• Measurable
• Achievable
• Relevant
• Time

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www.aace.com www.diabetes.org www.powerofpreventio
n.com www.fitness.gov www.presidentschallenge.org