Prediabetes Carol H. Wysham, MD. What is Diabetes? Normally, blood sugar (glucose) levels are kept...

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

Pancreas

Cannot Produce Enough Insulin

Body lacks insulin or is unable to use insulin

effectively

Diabetes

Muscle and Fat Cells

Cannot Use Insulin Effectively

How Food is Digested

1. Food enters stomach

5. Insulin unlocks receptors

4. Pancreas releases insulin

2. Food is converted into glucose

3. Glucose enters bloodstream

6. Glucose enters cell

• 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.

What Causes Diabetes

0

4

8

12

1980 1990 2000 (Estimated)•From Centers for Disease Control and Prevention, 2000.

•D

iag

no

se

d C

as

es

(M

illio

ns

)

•+17%

•+60%

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

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 6.9Narayan KMV et al JAMA 290: 1884, 2003

NHANES: Diabetes Prevalence by Age

0

2

4

6

8

10

12

14

18-29 30-39 40-49 50-59 60-69 >79

1990

1998

Age, in years

%

Source: CDC

$ spent on fast food

4.0

4.5

5.0

5.5

6.0

6.5

7.0

7.5

1990 1992 1994 1996 1998 2000

Diabetes Prevalence of obesity, increased by 61% since 1991

65% of US adults are overweight

BMI and weight gain major risk factors for diabetes

The Prevalence of Diabetes and Obesity

Pre

vale

nc

e

(%)

72

73

74

75

76

77

78Mean body weight

kg

Year

(70)

(110)

The Less You Exercise and the More You Watch TV, the Chances of Getting Diabetes Will Be

Significantly Increased!

Hu et al. Arch Intern Med. 2001;161:1542.

3.0

2.5

2.0

1.5

1.0

0.5

0>15.0

8.1-15.03.6-8.0 3.5

46.0

23.6-45.9

10.0-23.5

<10.0

Quartiles ofMET - hours per weekQuartiles of no. of hours

watching TV per week

RR

Not too long ago we were hunters and gatherers doing physical labor for our daily existence

The Evolution of Man: The Thrifty Gene Hypothesis

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

Retinopathy: 25x

Complications of Diabetes

End-Stage Kidney Disease: 17x

Heart Disease: 2-4x

Foot/Leg Amputations:

5x

Stroke: 2-6x

Changein HbA1C

Microvascular Complications

0

-1

-2

-3

-4

-5

United Kingdom Prospective Diabetes Study (UKPDS)

0

- 5

-10

-15

-20

-25

- 0.9%

- 25%

1% Decrease in HbA1c = 25% Decrease in Microvascular Risk!

Ch

ange

in H

bA

1c

% C

han

ge in

Rat

e of

C

omp

lica

t ion

s

Glucose Metabolism

Normal GlucoseMetabolism

Prediabetes Diabetes

0

220

180

160

140

120

100

200P

lasm

a g

luco

se (

mg

/dl)

Diabetes

IGT

Normoglycaemia

1 2 3Time following meal (hrs)

Harris MI. Diabetes Care 1993, 16: 642-652.

Glucose Levels in Normal, Glucose Levels in Normal, Prediabetic and Diabetic SubjectsPrediabetic and Diabetic Subjects

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

6.00

12.00

18

27

0.00

5.00

10.00

15.00

20.00

25.00

30.00

Normal IGT New DM Previous DM

% w

ith

CV

D

*MI=myocardial infarction.

Adapted from: Hu F, et al. Diabetes Care. 2002;25:1129-1134.

Prevention of Diabetes

The Finnish Diabetes Prevention Study: Lifestyle Modifications (cont’d)

0

20

40

60

80

Control (n=250) Diet intervention (n=256)

Inci

den

ce

of

dia

be

tes

(cas

es

/10

00 p

erso

n-y

ears

)

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)

-6

-5

-4

-3

-2

-1

0

Weight (kg) Waist (cm) SBP (mm Hg) DBP (mm Hg)

Control (n=250) Diet intervention (n=256)

Ch

an

ge

fro

m b

ase

line

Tuomilehto et al. N Engl J Med. 2001;344:1343.

P<0.001 P<0.001P=0.007 P=0.02

FDPS: Incidence of Diabetes By Success Score

0

5

10

15

20

25

30

35

40

0 1 2 3 4 5

Control

Intervention

Success Score

Inci

den

ce o

f D

iab

etes

(%

)

Tuomilehto et al. NEJM2001; 344: 1343

The Diabetes Prevention Program

Sponsored by the NIDDK, NIA, NICHD, NIH, IHS, CDC, ADA, Sponsored by the NIDDK, NIA, NICHD, NIH, IHS, CDC, ADA, and other agencies and corporationsand other agencies and corporations

A Randomized Clinical Trial to Prevent Type 2 Diabetes

in Persons at High Risk

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 % 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. 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

0

2

4

6

8

10

12

Placebo Metformin Intensivelifestyle

Ca

ses

/10

0 p

ers

on

-ye

ars

Average follow-up of 2.8 years

31%*

58%*

*All pairwise comparisons significantly different by group; sequential log-rank test.

The Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393.

Pancreas

Cannot Produce Enough Insulin

Body lacks insulin or is unable to use insulin

effectively

Diabetes

Muscle and Fat Cells

Cannot Use Insulin Effectively

Prevalence of IR in Selected Metabolic Disorders

Bonora E, et al. Diabetes. 1998;47:1643-1649.Haffner SM, et al. Am J Med. 1997;103:152-162.

IRHypertension: 58%

Hyperuricemia: 63%Hypertriglyceridemia: 84%

T2DM: 92%

Low HDL cholesterol: 88%

Those with multiple disorders (diabetes, hypertension, dyslipidemia, and hyperuricemia):

95%

• 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.

Who Is Insulin Resistant?

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

HypertensionHypertension

ObesityObesity

HyperinsulinemiaHyperinsulinemia

DiabetesDiabetes

DyslipidemiaDyslipidemia

Small, dense LDLSmall, dense LDL

InflammationInflammation

HypercoagulabilityHypercoagulability

InsulinInsulinResistanceResistance

InsulinInsulinResistanceResistance AtherosclerosisAtherosclerosisAtherosclerosisAtherosclerosis

Biological Functions of the Adipocyte

Fatty Acids Glucose

Fed

Fasted

Fatty Acids Glycerol

Leptin, FFA, TNF, IL-6,Adiponectin, Resistin, AngiotensinogenPAI-1, Other

Leptin

ANS

Secretory/Endocrine GlandInert Storage Depot

Kahn B, Flier J. J Clin Invest. 106:473 2000

Insulin

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 - 125

Prediabetes

> 125

Diabetes

< 100

Normal

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 ActivityPhysical Activity

++

Sound NutritionSound Nutrition

Good HealthGood Health

HealthThe first part of our equation is activity

Get moving, find something you enjoy

Physical Activity Pyramid

Prescription pad

Prescription pad

Activities Log

Week # Activity # of Minutes

Mon

Tue

Wed

Thu

Fri

Sat

SunParticipant’s signature: Date:

HealthThe 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 bodyweight. Lipids were slightly improved, but homocysteine and CRPboth 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

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

(NIH. Obes Res. 1998)

*In combination with diet, increased activity, and behavior modification.

Gastric Bypass Surgery for Obesity

Improvements in technique and“advertising” has resulted in aresurgence of interest in bariatricsurgery for treatment of obesity

1990 – 16,000/year2003 – 200,000/year

Healthy Lifestyle Improves All Cardiovascular Risk

Factors:Glucose

BPCholesterol

30-60 minutes/day

High fiber, low fat diet – 3 meals/day

Restrict:

CaloriesSaltSimple carbohydratesAnimal Fats

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?

Eat foods low

in fat & calories.

If overweight,

lose weight. Physical activity

Stop smoking!

Limit alcohol to 1-2 drinks per day.

Take your medications regularly.

What are goals to healthy living? Be SMART

Specific Measurable

AchievableRelevant Time

www.aace.com

www.diabetes.org

www.powerofprevention.com

www.fitness.gov

www.presidentschallenge.org