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Exercise and Endocrine Care

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Exercise and Endocrine Care Eric Sherman MAJ, USAF, MC Pediatric Endocrine Fellow Objectives Discuss the maintenance of euglycemia Review some basics of exercise ... – PowerPoint PPT presentation

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Title: Exercise and Endocrine Care


1
Exercise and Endocrine Care
  • Eric Sherman
  • MAJ, USAF, MC
  • Pediatric Endocrine Fellow

2
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

3
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

4
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

5
Pierce Br. J. Sports Med (1999)
6
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
7
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)

8
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

9
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

10
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

11
Types of insulin
  • Short acting
  • Regular
  • Aspart (Novolog) primary insulin in pumps
  • Lispro (Humalog)
  • Intermediate acting
  • NPH
  • Long acting
  • Detemir
  • Glargine (Lantus)

12
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
13
Diabetes and exercise
  1. Exercise may decrease risk of diabetes
    complications
  2. Hypoglycemia
  3. Increased risk of DKA
  4. Unmasking CAD

14
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)

15
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
16
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)

17
And now for some real data
18
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)

19
McMahon JCEM (2007)
20
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

21
McMahon JCEM (2007)
  • Lack of hypoglycemia from 5P MN
  • Elevated counter-regulatory hormones may have
    increased fatty acid oxidation

Growth Hormone
Fatty Acids
Cortisol
22
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)

23
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)

24
Conclusions
  • Glucose production ? glucose utilization
  • Counter regulatory hormones not doing their job,
    even in presence of hypoglycemia
  • Diabetes Care (2006)

25
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)

26
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)

27
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)

28
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)

29
DirecNet Diabetes Care (2006)
  • Hypoglycemia 3 times more
  • common in basal continued
  • group
  • Hyperglycemia 4.5 times
  • more common in basal stopped
  • group

30
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)

31
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)

32
Guelfi Diabetes Care (2005)
33
Guelfi Diabetes Care (2005)
34
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)

35
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)

36
Bussau Diabetes Care (2006)
37
Lactate
Fatty acids
Epinephrine
Norepinephrine
Growth hormone
Cortisol
Glucagon
Insulin
Bussau Diabetes Care (2006)
38
ADA and hypoglycemia
  • Avoid exercise if BG lt 100
  • Have carbohydrates available during exercise
  • ADA Position Statement Diabetes Care (2004)

39
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

40
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

41
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)

42
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)

43
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)

44
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)

45
Preparticipation evaluation
  • Vital signs
  • Complete PE including monofilament evaluation
  • A1C
  • Yearly eye exam
  • Microalbumin
  • Fasting lipid panel
  • TFTs
  • Consider formal cardiac stress test

46
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)

47
Exercise Retinopathy
ADA Position Statement Diabetes Care (2004)
48
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)

49
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)

50
Exercise autonomic dysfunction
  • Difficult to diagnose
  • Resting HR gt 100
  • Orthostasis
  • Delayed gastric emptying
  • Cardiac stress test

51
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)

52
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)

53
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)
54
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)

55
Exercise and Hyperthyroidism
  • No specific ATA recommendations
  • Increased metabolic state with increased O2
    consumption
  • Increased risk of atrial fibrillation and
    rhabdomyolysis
  • Kahaly Thyroid (2002)

56
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)

57
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)

58
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)

59
So what
  • LWPES and ESPE recommend that extra steroid
    dosing be considered when performing endurance
    sports
  • LWPES/ESPE Consensus Statement JCEM (2002)

60
CAH and High Intensity Exercise
Weise JCEM (2004)
61
Stress dose steroids??
Weise JCEM (2004)
62
CAH and Prolonged Exercise
Green-Golan JCEM (2007)
63
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

64
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