Exercise and Diabetes. “in some people suffering from this affliction, exercise can improve the condition and should be done regularly. In more extreme

Exercise and Diabetes

“in some people suffering from this affliction, exercise can improve the condition and should be done regularly. In more extreme cases its effects worsen the condition. These people should rest until the condition improves.”

-Sushruta in 600 BC.

1921192119211921

• Insulin was discovered

• Diabetes turned from a fatal disease to a treatable disease

• New challenges for clinicians and researchers

Why should people with diabetes exercise?

• Exercise generally lowers blood glucose resulting in decreased insulin or OHA requirements.

• CVD risk factors are potentially improved by regular exercise.

• Exercise may prevent or delay the progression of diabetes related complications.

• Exercise improves general health.

Outline

• Regulation of glucose fluxes during exercise

• Non-insulin dependent diabetes

• Insulin dependent diabetes

• Practical information

Control of Glucose Fluxes

during a Bout of Exercise

Substrates and Signals that Control Glucose Fluxes during Exercise

QuickTime™ and aBMP decompressor

are needed to see this picture.

Liver

Insulin

Brain


are needed to see this picture.Pancreas

Glucagon

Adipose

WorkingMuscle

GlycerolNEFA

LactateAmino Acids

Adrenal

Gly

GNG

IL6

Autonomic Nerve Activity


are needed to see this picture.

Epi?

Sensors Carotid Sinus Liver/Portal Vein Working Muscle

BloodGlucose

AminoAcids

Intestine

Adrenal

Glucose homeostasis is usually maintained despite increased glucose uptake by the working

muscle

0

20

40

60

80

100

0

1

2

3

4

5

-30 0 30 60

ModerateExercise

Blood Glucose

(mg/dl)

Rates of Glucose Entry and Removal

from the Blood

(mg•kg-1•min-1)

Time (min)

Entry

Removal

Endocrine and Sympathetic Nerve Response to Exercise

0

40

80

120

ArterialGlucagon

(pg/ml)

0

100

200

300

-60 -30 0 30 60 90 120 150

ArterialCatecholamines

(pg/ml)

Exercise

Time (min)

Glucagon

Insulin

Norepinephrine

Epinephrine

0

8

12

16

ArterialInsulin(µU/ml)

Changes in glucagon and insulin are the main regulators of hepatic

glucose production during exercise

0

2

4

6

7

60

3

1

5Glucagon

Insulin

and

Epinephrine

Time (minutes)

mg·kg-1·min-1

120

0

20

40

60

80

100

0

1

2

3

4

5

-30 0 30 60

ModerateExercise

Blood Glucose

(mg/dl)


from the Blood

(mg•kg-1•min-1)

Time (min)

Entry

Removal

0

20

40

60

80

100

0

1

2

3

4

5

-30 0 30 60

ModerateExercise

Blood Glucose

(mg/dl)


from the Blood

(mg•kg-1•min-1)

Time (min)

Entry

Removal

When glucose removal exceeds glucose entry, hypoglycemia ensues

When glucose entry exceeds glucose removal,

hyperglycemia ensues

0

20

40

60

80

100

0

1

2

3

4

5

-30 0 30 60

ModerateExercise

Blood Glucose

(mg/dl)


from the Blood

(mg•kg-1•min-1)

Time (min)

Entry

Removal

Non-insulin dependent diabetes

Views on ExerciseViews on Exercise

• Exercise and temperance can preserve something of our Exercise and temperance can preserve something of our early strength even in old age. early strength even in old age. Cicero (106-43 BC)Cicero (106-43 BC)


• Those who think they have not time to exercise will have Those who think they have not time to exercise will have to find time for illness. to find time for illness. Edward Stanley, Earl of Derby Edward Stanley, Earl of Derby (1826-1893)(1826-1893)


• Bodily exercise, when compulsory, does no harm to the Bodily exercise, when compulsory, does no harm to the body. body. Plato (428-348 BC)Plato (428-348 BC)


• Immature faddists are continuously proclaiming the value Immature faddists are continuously proclaiming the value of exercise; four people out of five are more in need of rest of exercise; four people out of five are more in need of rest than exercise. than exercise. Logan Clendening (1884-1945)Logan Clendening (1884-1945)


• I get my exercise acting as a pallbearer to my friends who I get my exercise acting as a pallbearer to my friends who exercise. exercise. Chauncey Depew (1834-1928)Chauncey Depew (1834-1928)


• To get back my youth I would do anything in the world, To get back my youth I would do anything in the world, except take exercise, get up early or be respectable. except take exercise, get up early or be respectable. Oscar Oscar Wilde (1854-1900)Wilde (1854-1900)


• I have never taken any exercise except sleeping and I have never taken any exercise except sleeping and resting. resting. Mark Twain (1835-1910)Mark Twain (1835-1910)


• If it weren't for the fact that the TV set and the refrigerator are so far apart, some of us wouldn't get any exercise at all. Homer Simpson (1961-2005)


• If by exercise you mean video games, then 2 h a day is If by exercise you mean video games, then 2 h a day is about right. about right. Micah Joe Wasserman (1991-present)Micah Joe Wasserman (1991-present)

People need to be Physically Active!

• Our genetic makeup has evolved based on a physically active culture of hunting and gathering and periods of feast and famine.

• In the absence of the need to hunt and gather and with food always available we need to make an effort to incorporate physical activity in our lives.

Genes determine Characteristics Genes determine Characteristics of the Bodyof the Body

To survive, people in early times had to have genes that permitted the body to store fuel in times of excess so that they would have a source of energy during times of famine.

Those genes that permit efficient food storage are termed, “Thrifty Genes”.

Thrifty genes cause rapid weight gain in times of abundant food supply.

The advantage of this trait is that the bearer is much more likely to survive in the absence of food.

“obesity is an unintentional consequence of societal

progress”

Dr. Phil

The Problem with Thrifty Genes….

The problem is that in a society where food is always plentiful and physical activity is not a part of the lifestyle, thrifty genes cause obesity, diabetes and related problems.

Because of the human genome it is necessary to re-introduce

physical activity into our lives.

Exercise Greases the Wheels

• blood flow• capillary recruitment• spatial barriers

Extracellular Membrane

• hexokinase #• hexokinase compartmentation• spatial barriers

Intracellular

glucose 6-phosphate

glucose

• transporter #• transporter activity

Regular exercise increases insulin-stimulated glucose

disposal in people with non-insulin-dependent diabetes

0

2

4

6

Glucose Disposalduring a

40 mU/m2·minInsulin Clamp

(mg/kg-FFM·min)

OxidativeNon-oxidative

Glucose Metabolism

Before AfterExercise Program (12 wks)

Regular exercise increases skeletal muscle GLUT4 content.

0

4

8

12

MuscleGLUT4Protein

(OD units/1000)

Before AfterExercise Program (12 wks)

Regular exercise reduces fasting blood glucose in people with non-insulin-

dependent diabetes.

FastingBlood GlucoseConcentration

(mg/dl)

Before AfterExercise Program (6-10 wks)

0

50

100

150

CVD risk factors are potentially

improved by regular exercise• Glucose Intolerance

• Hyperinsulinemia

• Hyperlipidemia

• Coagulation Abnormalities

• Hypertension

• Obesity

Insulin-dependent diabetes

Exercise-induced hypoglycemia

• While exercise-induced hypoglycemia is generally not common in non-insulin dependent diabetes, it is extremely prevalent in insulin dependent diabetes.

• Hypoglycemia may occur during exercise or after exercise (even up to 24 h following the cessation of an exercise session).

• Hypoglycemia can be prevented by eating more, taking less insulin, or both.

Endocrine and Sympathetic Nerve Response to Exercise

0

40

80

120

ArterialGlucagon

(pg/ml)

0

100

200

300

-60 -30 0 30 60 90 120 150

ArterialCatecholamines

(pg/ml)

Exercise

Time (min)

Glucagon

Insulin

Norepinephrine

Epinephrine

0

8

12

16

ArterialInsulin(µU/ml)

Humalog, Novolog

Regular

NPH

Lente

Ultralente, Lantus

0 4 208 1612 24

Rapid

Short

Intermediate

Intermediate

Long

Insulin Profiles

0 4 208 1612 24

Lantus (at bedtime) + Humalog (with meals)

Insulin adjustment scenarios

Moderate exercise Hypoglycemia!!

Moderate exercise Lower lunch & dinner Humalog

Hypoglycemia!

0 4 208 1612 24

Lente (at bedtime) + Humalog (with meals)

Insulin adjustment scenarios

Marathon training Hypoglycemia!!

Lower or even eliminate breakfast & lunch Humalog

Hypoglycemia!!

Marathon training

Exercise accelerates absorption of insulin from

subcutaneous depotExercise or

Continued Rest

Arterial Insulin

(U/ml)

Time (minutes)

SubQInsulin

-30 0 30 60

0

15

30

45Exercise

Rest

Insulin-stimulated glucose utilization is

increased during exercise

0

6

12

18

10 100 1000

Insulin (µU/ml)

GlucoseUtilization

(mg/kg·min)Rest

Exercise

1

Proposed mechanisms by which acute exercise enhances insulin sensitivity

• Increased muscle blood flow

• Increased capillary surface area

• Direct effect on working muscles

• Indirect effect mediated by insulin-induced suppression of FFA levels

Glucose tolerance is improved, and the body is more insulin sensitive

for an extended period after exercise.

0

10

40

60Area Underthe Blood

Glucose Curveduring an OGTT(mg/dl•min)

Pre-Exercise

6 h 12 h 1 day 2 day 4 day

90 min of ModerateExercise

Post-Exercise

Blood glucose increases during exercise in people with poorly-controlled diabetes

200

220

240

260

280

300

0

1

2

3

4

5

-30 0 30 60

ModerateExercise

Blood Glucose

(mg/dl)


from the Blood

(mg•kg-1•min-1)

Time (min)

Entry

Removal

Exercise-induced increase in portal vein glucagon is exaggerated by poorly-controlled diabetes

0

100

200

300

-50 0 50 100 150

Time (min)Time (min)

0

100

200

300

-50 0 50 100 150

ArterialImmunoreactive

Glucagon

(pg/ml)

ArterialPortal VeinHepatic Vein

Moderate ExerciseModerate Exercise

DiabeticNon-Diabetic

Sympathetic drive to the liver is increased during exercise in

diabetes

0

4

8

12

-50 0 50 100 150

Time (min)

Non-Diabetic

Diabetic

Moderate Exercise

Hepatic Norepinephrine

Spillover(ng·kg-1·min-1)

Practical Information

Factors that influence the response to acute exercise in the general population (including those with

diabetes)• Exercise intensity, duration, and type

• Fitness level

• Nutritional state

• Temporal relationship to meal

• Calories and content of meal

• Environmental factors

General Considerations in People with Diabetes

• Physical screening prior to starting an exercise program

• Metabolic control

• Blood glucose monitoring

• Food intake

• Insulin administration (when applicable)

• Make physical activity compatible with a person's lifestyle and interests

General Consideration 1: Physical screening prior to starting an exercise program

• Exercise stress test may be indicated to test myocardial function and to identify a suitable work intensity.

• Identify exercise modalities that might be contraindicated for specific complications.

• Discuss strategies for adjusting diet and therapy.

Heart Disease

Anaerobic Threshold Concept

250

Exercise

(watts)

0

5

10

15

Exercise

20015010050

Rest Period

Onset of lactic acidosis

Blood

Lactate

mM

Athlete

General Consideration 2: Metabolic Control

• If blood glucose <5 mM extra calories before exercise likely required.

• If blood glucose 5-12 mM extra calories probably not required.

• If blood glucose >12 mM measure urine ketones.– If urine ketones negative, exercise can be performed

and extra calories not required.– If urine ketones positive, take insulin and delay

exercise until ketones negative.

Glycemic responses to exercise in people with diabetes depends on metabolic control

0

100

200

300

-30 0 30 60 90

Time (min)

Exercise

Poor Control

Good Control

Intensive Control

Arterial Blood Glucose

(mg/dl)

General Consideration 3: Blood Glucose Monitoring

• Learn the glycemic response to different exercise conditions and in the post-exercise state.

• Identify when changes in therapy or food intake are necessary.

• For more extreme sports (e.g. skydiving, rock climbing, scuba diving), test blood sugar multiple times prior to exercise to establish a pattern.

General Consideration 4: Food Intake

• A source of CHO should be readily available during and after exercise.

• Consume CHO as needed to avoid hypoglycemia.

• Consume proteins & fats for prolonged exercise in order to prevent post-exercise hypoglycemia.

General Consideration 5: Insulin administration (when applicable)

• Be aware of interval of peak insulin action.

• Reduce the insulin dose if exercise is anticipated.

• Administer away from the working muscles.

General Consideration 6: Make physical activity compatible with a person's lifestyle and interests!

The three most important factors in determiningthe success of an exercise program are:

Compliance

Compliance

Compliance

Documents

Exercise and Diabetes. “in some people suffering from this affliction, exercise can improve the condition and should be done regularly. In more extreme