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
QuickTime™ and aBMP decompressor
are needed to see this picture.Pancreas
Glucagon
Adipose
WorkingMuscle
GlycerolNEFA
LactateAmino Acids
Adrenal
Gly
GNG
IL6
Autonomic Nerve Activity
QuickTime™ and aBMP decompressor
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)
Rates of Glucose Entry and Removal
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)
Rates of Glucose Entry and Removal
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)
Rates of Glucose Entry and Removal
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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Views on ExerciseViews on Exercise
• 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)
Rates of Glucose Entry and Removal
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