impact of exercise on patients with diabetes...

Impact of Exercise on Patients with Diabetes Mellitus

Bret Goodpaster, Ph.D. Exercise Physiologist

Assistant Professor of MedicineUniversity of Pittsburgh

Division of Endocrinology and Metabolism

Learning Objectives

After completing this section, you should be able to:1. Discuss the relative role of physical activity in body–

weight regulation, i.e., energy balance.2. Define insulin resistance and describe its role in the

development of type 2 diabetes.3. Compare and contrast the effects of exercise and

dieting on body weight, body composition and metabolism.

4. Debate the impact of exercise on glucose control.

Two Main Types of Diabetes Mellitus

Type 1• Insulin required to

live• Ketoacidosis

(⇑ Fat metabolism)• Weight Loss• Average onset = 11

years old

Type II• Not initially

dependent on insulin

• Insulin resistance/ insensitivity

• > 80% are overweight

• Average onset > 40 years

Results from the body's failure to produce insulin.

It is estimated that 5%–10% of Americans who are diagnosed with diabetes have type 1 diabetes.

Results from insulin resistance (a condition in which the body fails to properly use insulin), combined with relative insulin deficiency.

Most Americans who are diagnosed with diabetes have type 2 diabetes.

Type 2 Diabetes Type 1 Diabetes

Source: ADA website 2005

Type 2 Diabetes

>30 million worldwide ( 18.5 million in the United States)Many individuals do not know they have Type 2 diabetes90%–95% of all Diabetes mellitus is Type 2Increasing in incidence in last four decadesPopulation specific (Native Americans, Hispanic, African–American)

Risk Factors for Type 2 DiabetesRisk Factors for Type 2 Diabetes

Obesity

Body fat distribution

Family history of diabetes

Physical inactivity

Race/ethnicity

Age

Previous gestational diabetes (GDM)

Elevated fasting glucose levels

Impaired glucose tolerance

Obesity and Risk of Obesity and Risk of Type 2 DiabetesType 2 Diabetes

WomenMen

<23 24-24.9

25-26.9

27-28.9

33-34.9

<22 23-23.9

29-30.9

31-32.9

35+

1.0 1.00

5

93.2

42.1

10

40

70

100

Age

-adj

uste

d re

lativ

e ris

k

Body mass index (kg/m2)


Obesity



Physical inactivity

Race/ethnicity

Age




Risk of type 2 diabetes associated with level of physical activity

0

0.2

0.4

0.6

0.8

1

Q1 Q2 Q3 Q4 Q5Hu et al., JAMA 282:1433, 1999

Adjusted for age, smoking. hypertension,family history, menopause, high cholesterol

Quartile of physical activity vs Q1

Rel

ativ

eR

isk

-23% -25%-38% -46%

8 year follow-up

U.S. Nurses Health Study


Obesity



Physical inactivity

Race/ethnicity

Age




Regional fat distribution, type 2 diabetes and insulin resistance

Visceral Adipose Tissue

VAT= 75.7%Total Fat = 738.53 cm2

VAT= 20.5%Total Fat = 728.46 cm2

Association between visceral abdominal fat and Metabolic Syndrome

1.0

1.5

2.0

2.5

3.0

1.0

1.5

2.0

2.5

3.0

OR

% (9

5% C

I)

Normal Weight Overweight Obese

1.01.52.02.53.03.54.04.55.0

1.01.52.02.53.03.54.04.55.0

OR

% (9

5% C

I)

Normal Weight Overweight Obese

*

*

*

*

*

Men Women

Odds ratio (OR) calculated for 50 cm2 increment in visceral fat.Goodpaster et al. Archives of Internal Medicine, 165:777-783, 2005.

InsulinInsulinResistanceResistanceAging

Type 2diabetes

Obesity/sedentary life style

Genetics

Olefsky JM. In: Endocrinology. 2nd ed. 1989:1369-1388.Reaven GM. Clinical Diabetes. 1994;12:32-36.Seely BL, Olefsky JM. In: Insulin Resistance. 1993:187-252.

Other conditions:acromegalyCushing’s diseaselipodystrophyanti-insulin receptors

Insulin Resistance: Definitions

Insulin SensitivityAbility of insulin to lower circulating glucose• stimulate glucose utilization: muscle

and fat• suppress glucose production: liver

Insulin ResistanceCondition of low insulin sensitivity

How Does Insulin Resistance Lead to Type 2 Diabetes?

Saltiel AR, Olefsky JM. Diabetes. 1996;45:1661-1669.

Peripheral Tissues(Muscle)

Glucose

Liver

Receptor +postreceptor defects

Impaired insulin secretion

Insulinresistance

Pancreas

Increased glucose production

Progression to Type 2 DiabetesObesity

Sedentary lifestyleAging

Genetics

Insulin resistance

Hyperinsulinemia

Compensated insulin resistance Normal glucose tolerance


Kruszynska Y, Olefsky JM. J Invest Med. 1996;44:413-428.

Acquired

Insulin resistanceHepatic glucose outputInsulin secretion

Type 2 diabetes

GlucotoxicityFFA levels

Other

Acquiredβ-cell "failure"

Genetics

Insulin Resistance

Obesity and physical inactivity are both related to insulin resistance.

Obesity, Physical Activity and Energy Balance

Risk factor for cardiovascular disease, insulin resistance syndrome and type 2 diabetes.Energy balance is a primary factor involved in obesity, weight loss, weight maintenance.

Positive energy Positive energy balance = obesitybalance = obesity

Negative energy Negative energy balance = weight lossbalance = weight loss


Energy expenditure during walking can be predicted by walking speed and body weight.A 120-lb. person walking for 30 min will burn 3.6 Kcal/min, or 108 Kcal in 30 min. A 200-lb. person will burn ~160 Kcal at that speed in 30 min. It requires ~3500 Kcal to “burn” off a pound of body fat.Therefore, it will take a 120-lb. person 16.2 hours of walking, or 49 miles, to burn a pound of body fat!A 200-lb. person will have to walk only 34 miles!

Learning Activity

Use the table below to calculate approximately how many miles you would need to walk in order to burn a pound of body fat. Choose 2 different speeds to see how they compare.

Speed (mph) Body weight (lb.)80 100 120 140 160 180 200

kcal/min2.0 1.9 2.2 2.6 2.9 3.2 3.5 3.82.5 2.3 2.7 3.1 3.5 3.8 4.2 4.53.0 2.7 3.1 3.6 4.0 4.4 4.8 5.33.5 3.1 3.6 4.2 4.6 5.0 5.4 6.14.0 3.5 4.1 4.7 5.2 5.8 6.4 7.0


To put this in perspective, eating an average candy bar (~200 Kcal) only every other day for a month will add one pound of body fat!

Positive energy Positive energy balance = obesitybalance = obesity

Negative energy Negative energy balance = weight lossbalance = weight loss

Exercise for weight loss

Exercise is typically not effective by itself to induce substantial weight loss. Exercise, however, may help with long-term weight maintenance.Exercise may also benefit insulin resistance independent of weight loss.

Decreased risk for type 2 diabetes with increased physical activity

LOW MEDIUM HIGHPhysical Activity Level

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Kelley, D.E. and Goodpaster, B.H. Effects of Exercise on Glucose Homeostasis in Type 2 Diabetes Mellitus, MSSE 2001.

Exercise Training

Muscle Mass

Glucose Utilization

Blood Glucose Control

Intrinsic Muscle Properties

Blood Flow

Bioenergetics Fiber TypeCapillarynumber

Glucose Availability

Glucose Extraction

Glucose Storage Space

Insulin signaling pathwaysGLUT 4HexokinaseGlycogen synthase

LPLMitochondriaOxidativeenzymesCPT I

Triglyceride

?

Effect of the volume and intensity of exercise training on insulin sensitivity

Houmard et al. J Appl Phys, 2004.

0.0

2.0

4.0

6.0

8.0

10.0

12.0

0.0

2.0

4.0

6.0

8.0

10.0

12.0PRE

POST

EXERCISE DIET EXERCISE + DIET

GROUP

* **†

Goodpaster, Katsiaras and Kelley, Diabetes, 2003.

Exercise and Weight Loss Have Additive Effects on Insulin Sensitivity in Obese Subjects at Risk for the Development of Type 2 Diabetes

Exercise Training

Muscle Mass

Glucose Utilization

Blood Glucose Control

Intrinsic Muscle Properties

Blood Flow

Bioenergetics Fiber TypeCapillarynumber

Glucose Availability

Glucose Extraction

Glucose Storage Space

Insulin signaling pathwaysGLUT 4HexokinaseGlycogen synthase

LPLMitochondriaOxidativeenzymesCPT I

Triglyceride

?

Citation

Design

Subjects

Exercise Intensity/ Duration

Intervention Duration

Glucose control

Insulin Sensitivity

Insulin Secretion

Ronnemaa et al. 1986

RCT: Exercise

25 men and women

5-7x/wk; 70% VO2max 45 min

4 months HbA1c ↓1%; FPG ↓2hPPG ↓

NC Fasting insulin ↓ 2h PPI ↓

Uusitupa et al. 1996

RCT: Diet +Exercise

86 men and women

3-4x/wk; Aerobic 30-60

12 months HbA1c ↓0.5%; NC HbA1c in 50%; FPG ↓

NC Fasting insulin ↓

Leon et al. 1984

RCT: 5 types of Exercise intervention

50 men 2-4x/wk 70% VO2max 30-60min

3 months FPG ↓ HbA1c ↓ 2hPPG ↓ 60minEx

NC Fasting insulin ↓ PPI ↓

Krotkiewski et al. 1985

Non-Randomized

24 men and women

3x/wk 80% VO2max 50 min

3 months FPG ↓ 2hPPG ↓

↑ Fasting insulin ↓ PPI ↓

Bogardus et al. 1984

RCT: Diet+Exercise vs Diet only

18 men and women

3x/wk 75% VO2max 30 min

3 months FPG: No additional effect of exercise

Ex ↑ in Non-ox.

IVGT- Exercise ↓ vs Diet only

Poirier et al. 1996

Non-Randomized

11 men 3x/wk 60% VO2max 60 min

6 months FPG ↓ HbA1c ↓

NC Fasting insulin ↓

Reitmann et al. 1984,

Non-Randomized

6 men and women

5-6x/wk 75% VO2max 20-40 min

1.5-2.5 months FPG ↓ PPG ↓ HbA1c ND

NC HGP ↓

Fasting insulin ↓ PPI ↓

Effects of exercise on glucose homeostasis in type 2 diabetes

Changes During Acute Exercise

• Energy expenditure measured as the amount of oxygen utilization during high– intensity exercise can increase 20 X resting levels.

• Heart rate, blood pressure and cardiac output increase.

• Both fat and carbohydrate (glucose) can be used as fuel during exercise. Higher intensity = more glucose utilization, lower to medium intensity = more fat utilization.

Exercise Training : Long–Term Effects

Aids in blood glucose controlIncreases insulin sensitivityImproves blood lipidsDecreases blood pressureAids in weight reductionPhysical work capacity greaterPsychological improvements

“If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health”

- Hippocrates (460-377 B.C.)

Recommended Readings

1) Mokdad, A.H., et al., The continuing increase of diabetes in the US. Diabetes Care., 2001. 24(2): p. 412.

2) Ross, R., et al., Reduction in obesity and related comorbidconditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Annals of Internal Medicine, 2000. 133(2): p. 92-103.

3) Goodpaster, B.H., et al., Effects of weight loss on regional fatdistribution and insulin sensitivity in obesity. Diabetes, 1999.48(4): p. 839-847.

4) Goodpaster BH, et al.: Enhanced Fat Oxidation through Physical Activity is Associated with Improvements in Insulin Sensitivity in Obesity. Diabetes, 52:2191-2197, 2003.

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