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.
1921
• 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
Brain
Sensors
Carotid Sinus
Liver/Portal Vein
Working Muscle
Autonomic
Nerve
Activity
Adrenal
Adrenal
QuickTime™ and a
BMP decompressor
are needed to see this picture.
Epi
Intestine
?
Glycerol
NEFA
Pancreas
QuickTime™ and a
BMP decompressor
are needed to see this picture.
Glucagon
Insulin
Adipose
Amino
Acids
Lactate
Amino Acids
IL6
GNG
Gly
QuickTime™ and a
BMP decompressor
are needed to see this picture.
Liver
Blood
Glucose
Working
Muscle
Glucose homeostasis is usually maintained despite
increased glucose uptake by the working muscle
Moderate
Exercise
100
80
Blood Glucose
60
(mg/dl)
40
20
0
5
Rates of Glucose
Entry and Removal
from the Blood
(mg•kg-1•min-1)
4
3
Entry
2
Removal
1
0
-30
0
30
Time (min)
60
Endocrine and Sympathetic Nerve Response to
Exercise
Exercise
120
Arterial
Glucagon
(pg/ml)
16
Glucagon
80
12
40
8
Insulin
0
0
Norepinephrine
300
Arterial
Catecholamines
(pg/ml)
200
100
Epinephrine
0
-60
-30
0
30
60
Time (min)
90
120
150
Arterial
Insulin
(µU/ml)
Changes in glucagon and insulin are the main
regulators of hepatic glucose production during
exercise
7
6
5
mg·kg-1·min-1
4
Glucagon
3
and
2
Insulin
1
Epinephrine
0
60
Time (minutes)
120
Moderate
Exercise
100
80
Blood Glucose
60
(mg/dl)
40
20
0
5
Rates of Glucose
Entry and Removal
from the Blood
(mg•kg-1•min-1)
4
3
Entry
2
Removal
1
0
-30
0
30
Time (min)
60
When glucose removal exceeds glucose entry,
hypoglycemia ensues
Moderate
Exercise
100
80
Blood Glucose
60
(mg/dl)
40
20
0
5
Rates of Glucose
Entry and Removal
from the Blood
(mg•kg-1•min-1)
4
3
Entry
2
Removal
1
0
-30
0
30
Time (min)
60
When glucose entry exceeds glucose removal,
hyperglycemia ensues
Moderate
Exercise
100
80
Blood Glucose
60
(mg/dl)
40
20
0
5
Rates of Glucose
Entry and Removal
from the Blood
(mg•kg-1•min-1)
4
3
Entry
2
Removal
1
0
-30
0
30
Time (min)
60
Non-insulin dependent
diabetes
Views on Exercise
• Exercise and temperance can preserve something of our
early strength even in old age. Cicero (106-43 BC)
Views on Exercise
• Those who think they have not time to exercise will have
to find time for illness. Edward Stanley, Earl of Derby
(1826-1893)
Views on Exercise
• Bodily exercise, when compulsory, does no harm to the
body. Plato (428-348 BC)
Views on Exercise
• Immature faddists are continuously proclaiming the value
of exercise; four people out of five are more in need of rest
than exercise. Logan Clendening (1884-1945)
Views on Exercise
• I get my exercise acting as a pallbearer to my friends who
exercise. Chauncey Depew (1834-1928)
Views on Exercise
• To get back my youth I would do anything in the world,
except take exercise, get up early or be respectable. Oscar
Wilde (1854-1900)
Views on Exercise
• I have never taken any exercise except sleeping and
resting. Mark Twain (1835-1910)
Views 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 Exercise
• If by exercise you mean video games, then 2 h a day is
about right. 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
of 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
Extracellular
Membrane
glucose
6-phosphate
glucose
• blood flow
• capillary recruitment
• spatial barriers
Intracellular
• transporter #
• transporter activity
• hexokinase #
• hexokinase
compartmentation
• spatial barriers
Regular exercise increases insulin-stimulated
glucose disposal in people with non-insulindependent diabetes
6
Glucose Disposal
during a
40 mU/m2·min
Insulin Clamp
(mg/kg-FFM·min)
Glucose Metabolism
Non-oxidative
Oxidative
4
2
0
Before
After
Exercise Program (12 wks)
Regular exercise increases
skeletal muscle GLUT4 content.
12
Muscle
GLUT4
Protein
(OD units/1000)
8
4
0
Before
After
Exercise Program (12 wks)
Regular exercise reduces fasting blood
glucose in people with non-insulin-dependent
diabetes.
150
Fasting
Blood Glucose
Concentration
(mg/dl)
100
50
0
Before
After
Exercise Program (6-10 wks)
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
Exercise
120
Arterial
Glucagon
(pg/ml)
16
Glucagon
80
12
40
8
Insulin
0
0
Norepinephrine
300
Arterial
Catecholamines
(pg/ml)
200
100
Epinephrine
0
-60
-30
0
30
60
Time (min)
90
120
150
Arterial
Insulin
(µU/ml)
Insulin Profiles
0
Rapid
Humalog,
Novolog
Short
Regular
Intermediate
NPH
Intermediate
Lente
Long
Ultralente,
Lantus
4
8
12
16
20
24
Insulin adjustment scenarios
0
4
8
12
16
20
24
Lantus (at bedtime) +
Humalog (with meals)
Moderate exercise
Hypoglycemia!!
Moderate exercise
Lower lunch &
dinner Humalog
Hypoglycemia!
Insulin adjustment scenarios
0
4
8
12
16
20
24
Lente (at bedtime) +
Humalog (with meals)
Marathon training
Hypoglycemia!!
Marathon training
Lower or even
eliminate breakfast
& lunch Humalog
Hypoglycemia!!
Exercise accelerates absorption of insulin
from subcutaneous depot
Exercise or
Continued Rest
45
Exercise
Arterial
Insulin
30
(mU/ml)
15
SubQ
Insulin
Rest
0
-30
0
30
Time (minutes)
60
Insulin-stimulated glucose utilization is
increased during exercise
18
Exercise
Glucose
Utilization
(mg/kg·min)
12
Rest
6
0
1
10
100
Insulin (µU/ml)
1000
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.
60
Area Under
the Blood
Glucose Curve
during an OGTT
(mg/dl • min)
90 min of Moderate
Exercise
40
10
0
PreExercise
6h
12 h 1 day 2 day
Post-Exercise
4 day
Blood glucose increases during exercise in people
with poorly-controlled diabetes
Moderate
Exercise
300
280
Blood Glucose
260
(mg/dl)
240
220
200
5
Rates of Glucose
Entry and Removal
from the Blood
(mg•kg-1•min-1)
4
3
Entry
2
Removal
1
0
-30
0
30
Time (min)
60
Exercise-induced increase in portal vein glucagon is
exaggerated by poorly-controlled diabetes
Non-Diabetic
Moderate Exercise
300
Arterial
Immunoreactive
Glucagon
(pg/ml)
Arterial
Portal Vein
Hepatic Vein
200
Moderate Exercise
300
200
100
100
0
-50
Diabetic
0
50
Time (min)
100
0
150 -50
0
50
Time (min)
100
150
Sympathetic drive to the liver is increased during
exercise in diabetes
Moderate
Exercise
Non-Diabetic
12
Hepatic
Norepinephrine
Spillover
(ng·kg-1·min-1)
Diabetic
8
4
0
-50
0
50
100
Time (min)
150
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.
Anaerobic Threshold Concept
Exercise
15
Blood
Lactate
mM
Heart
Disease
Onset of lactic acidosis
10
5
Athlete
0
50
Rest Period
150
100
Exercise
(watts)
200
250
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
Exercise
Arterial
Blood Glucose
Poor Control
300
200
(mg/dl)
Good Control
100
0
-30
Intensive Control
0
30
Time (min)
60
90
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 determining
the success of an exercise program are:
Compliance
Compliance
Compliance