Exercise and Endocrine Care

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Exercise and Endocrine Care

• Eric Sherman
• MAJ, USAF, MC
• Pediatric Endocrine Fellow

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Objectives

• Discuss the maintenance of euglycemia
• Review some basics of exercise physiology
• Review exercise physiology in type 1 diabetes
• Review the literature on exercising safely with
  type 1 diabetes
• Review other endocrine disorders and any exercise
  recommendations

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Fasting state

• Reduced insulin secretion
• Increased levels of cortisol, GH, glucagon and
  epinephrine
• Glucose production enhanced
• Mobilization of fatty acids for energy
• Sperling Pediatric Endocrinology

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Fed state

• Increased insulin secretion (w/in 20-30 min) and
  decreased glucagon secretion
• Glycogen synthesis enhanced
• Enhanced glucose uptake in muscle
• Suppression of gluconeogenesis
• Lipid synthesis activated and lipolysis
  suppressed
• Sperling Pediatric Endocrinology

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Pierce Br. J. Sports Med (1999)
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Exercise physiology
Decline in serum glucose
Increased glucagon secretion
Increased counter- regulatory hormones
Decreased plasma insulin secretion
Muscular glucose production Fatty acids
mobilized from adipose tissue Gluconeogenesis
from lactate (liver) GLUT4 stimulated transport
of glucose into muscle
Euglycemia maintained
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After exercise

• Similar to fasting state
• Goal to rebuild skeletal muscle glycogen stores
• Increased GLUT4 transport (insulin not initially
  required)
• Full replenishment of muscle stores requires
  insulin
• Pierce Br. J. Sports Med (1999)

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Counter regulatory hormones

• Glucagon (alpha cells in pancreas)
• Most efficient stimulator of gluconeogenesis
• Requires liver glycogen stores to acutely
  increase BG
• Growth hormone (anterior pituitary)
• Impaired glucose uptake
• Promotes lipolysis
• Increased hepatic glucose production
• Sperling Pediatric Endocrinology

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Counter regulatory hormones

• Cortisol (adrenal cortex)
• Enhances gluconeogenesis
• Epinephrine (adrenal medulla)
• More potent than norepi
• Inhibit insulin secretion
• Increase glucose secretion from liver and lactate
  from muscle
• Norepinephrine (same as epi)
• Sperling Pediatric Endocrinology

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Quick Primer on Type 1 Diabetes

• Incidence 20/100,000/year in US and ?
• Immune destruction of pancreatic beta cells
• Up to 40 of patients present after age 18
• Treatment insulin
• Prevention trials have all failed

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Types of insulin

• Short acting
• Regular
• Aspart (Novolog) primary insulin in pumps
• Lispro (Humalog)
• Intermediate acting
• NPH
• Long acting
• Detemir
• Glargine (Lantus)

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Insulin regimens

• Traditional
• NPH regular (now Novolog/Humalog) in AM
• Novolog at dinner
• NPH at bedtime
• Basal-bolus
• Lantus once daily Novolog at meals
• CSII (insulin pump)

Intensive treatment
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Diabetes and exercise

1. Exercise may decrease risk of diabetes
   complications
2. Hypoglycemia
3. Increased risk of DKA
4. Unmasking CAD

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What is different in diabetes

• Constant non-physiologic insulin supply
• Variable insulin absorption
• Suboptimal release of counter-regulatory hormones
  (especially during sleep)
• Increased skeletal muscle uptake following
  exercise
• Increased insulin sensitivity after exercise
• McMahon JCEM (2007)

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Exercise physiology in diabetes
Decline in serum glucose
Increased glucagon secretion
Increased counter- regulatory hormones
Decreased plasma insulin secretion
Muscular glucose production Fatty acids
mobilized from adipose tissue Gluconeogenesis
from lactate (liver) ?GLUT4 stimulated
transport of glucose into muscle
Hypoglycemia
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Hypoglycemia

• Older data suggests that risk of hypoglycemia
  lasts up to 31 hours after exercise Macdonald
  Diabetes Care (2007)
• 2-4 of deaths in type 1 diabetes attributed to
  hypoglycemia Cryer Diabetes Care (2003)
• 2 episodes per week of severe hypoglycemia in
  well controlled diabetics Cryer Diabetes Care
  (2003)
• One episode of hypoglycemia blunts responses to
  subsequent hypoglycemia for several days Hopkins
  Diab Res Clin Prac (2004)

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And now for some real data
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Biphasic Hypoglycemia

• 9 Australian adolescents exercised at 55 VO2
  peak (compared with 45 minutes of rest)
  moderate intensity
• Euglycemic clamp with constant insulin infusion
  and glucose adjusted to keep BG between 90-108
• Primary endpoint hypoglycemia as measured by
  increased GIR
• McMahon JCEM (2007)

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McMahon JCEM (2007)
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McMahon JCEM (2007)

• Early hypoglycemia
• Lack of physiologic decrease in insulin secretion
• Late hypoglycemia (MN 4AM)
• Imbalance between glucose production and use
• Need to replete glycogen stores
• Blunted counter-regulatory responses during sleep

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McMahon JCEM (2007)

• Lack of hypoglycemia from 5P MN
• Elevated counter-regulatory hormones may have
  increased fatty acid oxidation

Growth Hormone
Fatty Acids
Cortisol
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DirecNet

• A multi-center trial that studied the impact of
  exercise under a variety of conditions on 50
  children with type 1 diabetes
• 75 minute exercise session at 4PM (55 VO2 max)
• 11/50 hypoglycemic (23) BG lt 60
• 26/50 had BG lt 70 at some point
• Sharp rise in GH, but no change in cortisol or
  glucagon secretion
• Diabetes Care (2006)

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DirecNet

• Initial BG lt 120
• 86 hypoglycemic, 100 BG lt 70
• Initial BG 120-180
• 13 hypoglycemic, 44 BG lt 70
• Initial BG gt 180
• 6 hypoglycemic, 28 BG lt 70
• Diabetes Care (2006)

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Conclusions

• Glucose production ? glucose utilization
• Counter regulatory hormones not doing their job,
  even in presence of hypoglycemia
• Diabetes Care (2006)

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DirecNet

• 10P 6A - mean BG 131 on exercise days and 154
  on sedentary days
• Twice as many hypoglycemic events between 10P
  6A on days with exercise compared to sedentary
  days
• J Peds (2005)

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How many carbs before exercise?

• 9 adult subjects on NPH and Novolog exercised
  for 60 minutes (50 VO2 max) with euglycemic
  clamp 3 hours post breakfast
• Given 0, 15 30 g of carbs prior to exercise
• Based on GIR and amount of pre-exercise carbs, a
  regression equation calculated
• 35 g of carbs prevents acute hypoglycemia
• 40 g of carbs prevents acute and late
  hypoglycemia
• Dube Med Sci in Sports Exercise (2005)

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Reduction in pre-meal insulin

• 8 adult males in randomized crossover trial
• Exercised at 25, 50 75 of VO2 max for 30 and
  60 minutes (90 minutes after eating)
• Injected 25, 50 100 of typical Humalog dose
• 100 of Humalog dose associated with
  significantly reduced BG compared with dose
  reduction (all groups)
• Rabasa Lhoret Diabetes Care (2001)

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Insulin pumps

• Is suspending them an option?
• 50 patients aged 8-17 in random crossover trial
  (on and off pump during 75 minutes of exercise at
  55 VO2 max)
• DirecNet Diabetes Care (2006)

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DirecNet Diabetes Care (2006)

• Hypoglycemia 3 times more
• common in basal continued
• group
• Hyperglycemia 4.5 times
• more common in basal stopped
• group

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Another pump study

• 10 patients exercised for 45 minutes (60 VO2
  max) with pump on and pump off
• Wore CGMS for 24 hours after exercise
• No difference in hypoglycemic events during
  exercise (2 in each group)
• All 10 had 1-3 hypoglycemic events (BG 50-70)
  from 2.5 to 12 hours after exercise
• Admon Pediatrics (2005)

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Higher intensity exercise

• 7 adults
• 30 minutes of moderate exercise (40 VO2 max)
• 30 minutes of intermittent high intensity
  exercise (40 VO2 max 4s sprints every 2
  minutes)
• IHE felt to mimic typical toddler activity and
  adolescent sports
• Guelfi Diabetes Care (2005)

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Guelfi Diabetes Care (2005)
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Guelfi Diabetes Care (2005)
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Why the difference?

• Lactate
• Inhibit glucose uptake within skeletal muscle
• Stimulate hepatic gluconeogenesis
• Catecholamines
• Inhibit insulin mediated glucose uptake
• Stimulate hepatic gluconeogenesis
• GH
• Inhibit insulin mediated glucose uptake
• Guelfi Diabetes Care (2005)

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A novel approach

• 7 adult males with type 1 diabetes in random
  crossover trial
• Exercised for 20 minutes at 40 VO2 max /- a 10
  s sprint at completion of exercise
• Theorized that a short sprint would prevent
  hypoglycemia
• Increase in lactate catecholamines
• Bussau Diabetes Care (2006)

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Bussau Diabetes Care (2006)
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Lactate
Fatty acids
Epinephrine
Norepinephrine
Growth hormone
Cortisol
Glucagon
Insulin
Bussau Diabetes Care (2006)
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ADA and hypoglycemia

• Avoid exercise if BG lt 100
• Have carbohydrates available during exercise
• ADA Position Statement Diabetes Care (2004)

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My recommendations

• Avoid exercise if BG lt 100 or gt 300
• Check ketones if BG gt 250 and exercising
• Take 15 g of carbohydrates for every 30 minutes
  of exercise
• Check BG every 30-60 minutes during exercise and
  as needed
• Avoid using legs for injections p/t running
  (increased absorption) abdomen better

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My recommendations

• Check BG after exercise
• Disconnect pump during moderate to high intensity
  exercise, most sporting events and swimming
• Check BG prior to bedtime and eat snack with both
  carbohydrates and protein
• Check BG at 2A on intense exercise days

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Insulin adjustment

• No ADA recommendations
• No consensus statements
• Depends on timing spontaneity of exercise
• Data suggests a 50 reduction in pre-meal insulin
  for planned exercise
• 25 decrease in evening Glargine if morning
  exercise planned
• Pierce Br. J. Sports Med (1999)

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Insulin adjustment

• Post exercise
• Consider decrease in insulin dose of 25-50
• Elite athletes
• 50-75 reduction in total daily insulin dose
• Hypoglycemia can occur up to 24-36 hours after
  competition (restoring muscle glycogen)
• Pierce Br J Sports Med (1999)

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Exercise Hyperglycemia

• Physiology
• Insulin deficiency
• Hepatic glucose production continues without
  glucose utilization (exaggerated hyperglycemia)
• Increased lipolysis leads to FA and ketone
  production (exaggerated ketosis)
• Zinker Clinics in Sports Med (1999)

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ADA and hyperglycemia

• Avoid exercise if BG gt 250 and ketones present
• Use caution if BG gt 300 and no ketones are
  present
• ADA Position Statement Diabetes Care (2004)

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Preparticipation evaluation

• Vital signs
• Complete PE including monofilament evaluation
• A1C
• Yearly eye exam
• Microalbumin
• Fasting lipid panel
• TFTs
• Consider formal cardiac stress test

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Exercise cardiovascular dz

• Stress test if
• Age gt 35
• Age gt 25 and
• Type 2 diabetes for 10 years
• Type 1 diabetes for 15 years
• Other CAD risk factors
• Retinopathy or nephropathy
• PVD
• Peripheral neuropathy
• ADA Position Statement Diabetes Care (2004)

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Exercise Retinopathy
ADA Position Statement Diabetes Care (2004)
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Exercise and Nephropathy

• No specific recommendations
• ADA says high intensity/strenuous exercise should
  be avoided unless BP monitoring available
• Treatment may limit exercise capacity
• ADA Position Statement Diabetes Care (2004)

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Exercise and peripheral neuropathy

• Loss of sensation in feet increases risk of
  ulcers
• Contraindicated Allowed
• Treadmill Swimming
• Prolonged walking Biking
• Jogging Rowing
• Stairmaster Chair/arm exercises
• ADA Position Statement Diabetes Care (2004)

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Exercise autonomic dysfunction

• Difficult to diagnose
• Resting HR gt 100
• Orthostasis
• Delayed gastric emptying
• Cardiac stress test

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Type 2 diabetes

• Exercise benefits more clearly defined
• ? HDL cholesterol, ? Total chol, LDL chol, TG
• ? BP
• ? insulin sensitivity
• ? weight loss (? insulin resistance)
• ? fatal cardiac events
• Armen Clin Sports Med (2003)

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Type 2 Diabetes

• Decreased risk of hypoglycemia when taking oral
  agents
• Insulin therapy
• Incidence of hypoglycemic events similar to type
  1 diabetics when patients matched for duration of
  insulin therapy Hopkins Diab Res Clin Prac (2004)
• Increased carbohydrate intake and BG monitoring
  prior to exercise recommended Diabetes Care (2004)

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Hemodynamic changes in thyroid disease
Hyperthyroidism Hyperthyroidism Hypothyroidism
Peripheral vascular resistance ? ?
Circulation time ?? ?
Cardiac output ? ?
Stroke volume ? ?
Cardiac index ? ?
Arterial resistance ? ?
Venous resistance ?
Systolic/diastolic function ? ?
Systolic blood pressure ? ?
Pulse pressure widened narrow
Kahaly Thyroid (2002)
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Exercise and Hypothyroidism

• No specific ATA recommendations
• Limited data about exercise in treated patients
• Subclinical hypothyroidism
• No change in exercise parameters after 1 year of
  treatment (TSH 4.65 before treatment and 1.28
  after treatment)
• Caraccio JCEM (2005)

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Exercise and Hyperthyroidism

• No specific ATA recommendations
• Increased metabolic state with increased O2
  consumption
• Increased risk of atrial fibrillation and
  rhabdomyolysis
• Kahaly Thyroid (2002)

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Exercise and Hyperthyroidism

• What we recommend
• Avoid exercise until T3 and T4 levels are
  normalized (may take several weeks)
• TSH may remain suppressed for several months (no
  impact on exercise tolerance)

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Brief case report

• 45 yo white male with sarcoidosis
• Treated with prolonged steroid taper over 3 years
  (was on 2.5 mg/day at time of death)
• On Atenolol for 1 year for HTN
• Collapsed died in June 1983 3.5 miles into
  marathon in Sheffield, England
• Parsons Br J Sports Med (1984)

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Brief case report

• Missed Prednisone 2 days prior to race and on
  race day
• Autopsy revealed cortical atrophy and lipid
  depletion of adrenal glands (total weight 4 g)
• Parsons Br J Sports Med (1984)

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So what

• LWPES and ESPE recommend that extra steroid
  dosing be considered when performing endurance
  sports
• LWPES/ESPE Consensus Statement JCEM (2002)

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CAH and High Intensity Exercise
Weise JCEM (2004)
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Stress dose steroids??
Weise JCEM (2004)
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CAH and Prolonged Exercise
Green-Golan JCEM (2007)
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Review

• Discussed the maintenance of euglycemia
• Reviewed some basics of exercise physiology
• Discussed exercise physiology in type 1 diabetes
• Reviewed the literature on exercising safely with
  type 1 diabetes
• Discussed other endocrine disorders and any
  exercise recommendations

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Questions