hormonal changes and diabetes - it can be a bumpy ride!
DESCRIPTION
Presentation by Dr. Erin Keely (MD, FRCPC) at the Diabetes Perspectives... Ages and Stages Symposium (September 29, 2014)TRANSCRIPT
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Hormonal Changes and Diabetes- It can be a bumpy ride!!
Erin Keely Chief, Division of Endocrinology and
Metabolism, The Ottawa Hospital [email protected]
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Objectives
• Outline how hormonal changes affect insulin resistance and blood glucose levels
• Discuss how pregnancy impacts glucose control in women with diabetes and predicts risk of future diabetes in those with gestational diabetes
• Define androgen deficiency and how to screen for it in men with erectile dysfunction
• Describe impact of menopause and hormone replacement therapy for women with diabetes
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Gender differences in diagnosis of diabetes
• Women more likely to be diagnosed with postprandial glucose levels vs fasting levels • Might miss women if only do a fasting glucose
• Reasons not clear
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Impact of Pregnancy on Glucose Control
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What’s the difference between type 1 and 2 for pregnancy?
• Comorbidities – type 1 – autoimmune - thyroid disorders, nephropathy – type 2 - hypertension, hyperlipidemia, obesity, PCOD
• Treatment – oral agents vs. insulin – Type 2 often on statins, multiple antiHTN
• Pre-pregnancy care – type 2 may be considered less severe – older, often recent immigrants – May have low expectations of fertility – Health care providers – Self management
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Why is preconception care important? • Reduction of congenital anomalies • Reduction of spontaneous losses • Optimization of complications and associated conditions
– And encourage effective contraception until obtained
• Modify therapies if appropriate – Change to safest medications – Avoidance of disruption of effective glycemic and
blood pressure control
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Glucose is a teratogen
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Change to insulin prepregnancy unless using metformin for ovulation induction
But if conceive on oral agents do not stop medications until insulin
is started HYPERGLYCEMIA IS WORSE
THAN THE MEDICATIONS
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Target: A1c < 0.07
HgbA1c and Congenital Anomalies
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+ve pregnancy test MD appt
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First trimester changes • Fasting glucose falls
– first change – nadir of 3.5 mmol/l in 1st trimester
• Increased hypoglycemia unawareness – decreased counter regulatory response
• Rapid acting insulin takes longer to work – Need to take in advance of meal
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0
10
20
30
40
50
60
0 5 10 15 20 25 30 35 40
Weeks of Pregnancy
Prolactin Cortisol
HPL
Progesterone
HCG
hGH--V
Changes in Hormones of Pregnancy During Gestation
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Insulin requirements increase 2-3 fold during 2nd and 3rd trimester
• Is a GOOD thing • Sign of a healthy placenta • If requirements start
dropping suggests placental insufficiency – Small for gestational age,
fetal death, pre-eclampsia, placental abruption
Padmanabhan et al, Diabetes Care Oct 2014
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Higher risk of DKA in pregnancy • Accelerated starvation state
– Faster to make ketones
• Increased GFR – Will spill glucose at lower serum glucose levels – Blood glucose will not be as high when getting ketotic – Need high index of suspicion even if glucose only 14-16 mmol/l
• Less buffering ability – Compensated respiratory alkalosis – Renal excretion of HCO3 – worse acidosis
• Insulin resistance – need higher doses of insulin to reverse
• Risk to fetus – up to 50% mortality
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Peripartum
• Discontinue s.c. insulin when in active labour or if having elective c-section
• use IV insulin peripartum • restart s.c. insulin when eating
– 2/3 of prepregnancy dose
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Interpregnancy care
• Personal experience of a poor pregnancy outcome does not encourage and may even discourage high-risk women from attending preconception care
• Need to provide postpartum support and
ongoing care • what would help you be bettered prepared for your
next pregnancy? • what would make this difficult?
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Gestational Diabetes
• Carbohydrate intolerance with onset or first recognition in pregnancy –NOT IN 2013
• 2-4% of pregnancies- NOT IN 2013 • Same risk factors as type 2 diabetes
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Reasons to look for GDM
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Diagnostic criteria for GDM
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HAPO: Incidence of Adverse Outcomes for Glucose Categories (OR 1.75 or 2.0 )
Metzger BE, et al. HAPO. NEJM 2008;358(19):1991-2002.
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2013 GDM Diagnosis: Two Approaches 2013
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To diagnose overt diabetes in first trimester
IADSPG Consensus Panel, Diab Care 2010
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Gestational Diabetes Predicts Type 2 Diabetes
The Fourth Trimester
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Rates of Postpartum Type 2 Diabetes in Mothers with GDM
• Women with GDM have 20% risk of type 2 diabetes within 9 years compared to 2% in women without GDM
Feig, CMAJ July 29, 2008
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Risk of postpartum GDM predicted by rate of abnormal glucose tolerance in pregnancy
Kramer, Diab Care online Sept 2014
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Risk perception
N=89, 9-11 yr postpartum, Ottawa – 32% no idea/no different – 33% increased a little – 35% increased a lot – 15% had previously undiagnosed diabetes – 48% had abnormal GTT
Malcolm, Obstetric Medicine 2009;2:107-10
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• rate of postpartum screening increased from 14% to 60% if a reminder was sent to the patient, her family physician or both
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Breastfeeding associated with better maternal and offspring outcomes • May reduce offspring obesity and risk of type 2
diabetes • Lactation may attenuate unfavourable metabolic
risk factors, promote pp weight loss – Gunderson Obstet Gynecol 2007
Need to target this group for breastfeeding support
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Exclusive Breastfeeding on d/c
T1 Diabetes
Type 2 Diabetes
GDM Others
2007-2008
40% (83%)
46% (88%)
57% (90%)
66% (89%)
2008-2009
36% (87%)
51% (86%)
49% (91%)
62% (89%)
Source: BORN Ontario (Niday Perinatal Database)
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Postpartum GDM Management Checklist
1. Encourage Breastfeeding
2. 75g OGTT between 6 weeks - 6 months postpartum to detect prediabetes or diabetes
3. Discuss increased long-term risk of diabetes – Importance of returning to pre-pregnancy weight
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Case
• A 53 year old man with newly diagnosed diabetes is referred for education and self management. He has not been started on any medications yet. He has noticed some erectile dysfunction
• He has been reading online and asks about taking testosterone supplements to improve his glucose levels
• You advise him….
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Causes of erectile dysfunction
• Psychological • Organic
– Vascular • Strong predictor of other
cardiovascular disease
– Neurological – Hormonal
• All men with ED should have testosterone (LH, FSH, Prolactin) done
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What does testosterone do?
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Control of Androgen Production
• Primary hypogonadism – Testicular failure – High LH, FSH
• Secondary hypogonadism – Hypothalamic or
pituitary cause – Low FSH and LH
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Late onset androgen deficiency
• Gradual decline in androgen levels in aging
• Biochemical test vs.
symptom complex
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How do we diagnose androgen deficiency?
• What is normal? – Can 30% of men with
diabetes really have low testosterone?
• Which test to use – Total testosterone or free
testosterone
• Total testosterone – Normal > 12 nmol/l – Abnormal < 8 nmol/l
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Association of Androgen Deficiency and Type 2 Diabetes
• Testosterone deficiency more likely in men with type 2 diabetes
• Diabetes/metabolic syndrome more likely in men with testosterone deficiency
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Low testosterone levels associated with lower survival rates
Traish, Am J Med 2011
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So what about testosterone replacement in men with diabetes? • Goals
– Lipid profile – Decreased
atherogenesis – Improved bone health – Improved overall
health – Increased survival
• Evidence – Decreases HDL – Improved mortality – UNLESS known heart
disease (men undergoing angiography had 29% higher all cause mortality if put on androgens)
– No studies on bone health and diabetes
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Improvement in glycemic control in new diagnosis
• 32 men with new diabetes randomized to diet and exercise vs. diet/exercise and testosterone
• Improved glycemic control with no medications
• Improved lipid profile
With testosterone replacement
Heufelder J Androl 2009
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Testosterone replacement
• Needs to be followed carefully – Testosterone levels – Hematocrit – PSA – Clinical response
• Relief of symptoms • Bone health • Metabolic syndrome
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Goals of treatment
• Relief of symptoms • Bone health • ?improvement in metabolic syndrome
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Case
• A 53 year old man with newly diagnosed diabetes is referred for education and self management. He has not been started on any medications yet. He has noticed some erectile dysfunction
• He has been reading online and asks about taking testosterone supplements to improve his glucose levels
• You advise him….
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Menopause and Diabetes
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Definition of menopause
• Perimenopause – Irregular menses – cycle length variation of
more than 7 days from usual • Menopause
– 12 months of amenorrhea
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Symptoms of menopause
• Vasomotor • Vaginal dryness • Urinary incontinence • Sleep disturbance
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Important menopausal issues for women with diabetes • Women with Type 1 diabetes may go through menopause earlier
– Conflicting data – one study suggested 6 fewer fertile years in type 1 diabetes – Autoimmune premature ovarian failure in women with type 1
• Women with diabetes may have difficulty distinguishing hot flashes from hypoglycemia
• Increased abdominal fat, decreased lean body mass associated with menopause – Increased insulin resistance
• Women with type 2 diabetes at more risk of endometrial and maybe breast cancer • Osteoporosis
– Lower BMD more common in women with type 1 diabetes compared to women without diabetes
– Higher BMD in women with type 2 diabetes (lower if on glitazones) – Despite BMD fractures more common- ?more falls, change in bone structure, vascular
changes • increased risk of foot fractures with exercise
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Effects of HRT in women with diabetes
1. Impact on glucose control – Reduced insulin resistance
• Lower fasting glucose levels compared to no HRT in women with diabetes
• 30% reduction in incidence of diabetes in women taking HRT vs. no HRT
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2. Impact on CV risk -avoid in all women
with known CV disease
3. Risk of breast cancer 4. Benefits for
osteoporosis 5. Severity of vasomotor
symptoms
AACE guidelines 2011
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Summary
• Any change in sex hormone levels may impact risk of having diabetes and change glucose levels in individuals with diabetes
• In general, hormone replacement does not worsen glucose control or lipid levels. Biggest risk is in individuals known to have CV disease
• Men with diabetes more likely to be hypogonadal but full understanding of risks/benefits and best approach to replacing androgens in not known
• Women with diabetes have unique issues that need to be identified during menopause – Risk/benefits of hormone replacement is an individual decision between
the patient and her