56
Hormonal Changes and Diabetes- It can be a bumpy ride!! Erin Keely Chief, Division of Endocrinology and Metabolism, The Ottawa Hospital [email protected]

Hormonal Changes and Diabetes - It can be a bumpy ride!

Embed Size (px)

DESCRIPTION

Presentation by Dr. Erin Keely (MD, FRCPC) at the Diabetes Perspectives... Ages and Stages Symposium (September 29, 2014)

Citation preview

Page 1: Hormonal Changes and Diabetes - It can be a bumpy ride!

Hormonal Changes and Diabetes- It can be a bumpy ride!!

Erin Keely Chief, Division of Endocrinology and

Metabolism, The Ottawa Hospital [email protected]

Page 2: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 3: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 4: Hormonal Changes and Diabetes - It can be a bumpy ride!

Impact of Pregnancy on Glucose Control

Page 5: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 6: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 7: Hormonal Changes and Diabetes - It can be a bumpy ride!

Glucose is a teratogen

Page 8: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 9: Hormonal Changes and Diabetes - It can be a bumpy ride!

Target: A1c < 0.07

HgbA1c and Congenital Anomalies

Page 10: Hormonal Changes and Diabetes - It can be a bumpy ride!

+ve pregnancy test MD appt

Page 11: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 12: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 13: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 14: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 15: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 16: Hormonal Changes and Diabetes - It can be a bumpy ride!

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?

Page 17: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 19: Hormonal Changes and Diabetes - It can be a bumpy ride!

Diagnostic criteria for GDM

Page 20: Hormonal Changes and Diabetes - It can be a bumpy ride!

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.

Page 21: Hormonal Changes and Diabetes - It can be a bumpy ride!

2013 GDM Diagnosis: Two Approaches 2013

Page 22: Hormonal Changes and Diabetes - It can be a bumpy ride!

To diagnose overt diabetes in first trimester

IADSPG Consensus Panel, Diab Care 2010

Page 23: Hormonal Changes and Diabetes - It can be a bumpy ride!

Gestational Diabetes Predicts Type 2 Diabetes

The Fourth Trimester

Page 24: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 25: Hormonal Changes and Diabetes - It can be a bumpy ride!

Risk of postpartum GDM predicted by rate of abnormal glucose tolerance in pregnancy

Kramer, Diab Care online Sept 2014

Page 26: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 27: Hormonal Changes and Diabetes - It can be a bumpy ride!

• rate of postpartum screening increased from 14% to 60% if a reminder was sent to the patient, her family physician or both

Page 28: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 29: Hormonal Changes and Diabetes - It can be a bumpy ride!

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)

Page 30: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 31: Hormonal Changes and Diabetes - It can be a bumpy ride!
Page 32: Hormonal Changes and Diabetes - It can be a bumpy ride!
Page 33: Hormonal Changes and Diabetes - It can be a bumpy ride!
Page 34: Hormonal Changes and Diabetes - It can be a bumpy ride!

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….

Page 35: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 36: Hormonal Changes and Diabetes - It can be a bumpy ride!

What does testosterone do?

Page 37: Hormonal Changes and Diabetes - It can be a bumpy ride!
Page 38: Hormonal Changes and Diabetes - It can be a bumpy ride!

Control of Androgen Production

• Primary hypogonadism – Testicular failure – High LH, FSH

• Secondary hypogonadism – Hypothalamic or

pituitary cause – Low FSH and LH

Page 39: Hormonal Changes and Diabetes - It can be a bumpy ride!

Late onset androgen deficiency

• Gradual decline in androgen levels in aging

• Biochemical test vs.

symptom complex

Page 40: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 41: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 42: Hormonal Changes and Diabetes - It can be a bumpy ride!
Page 43: Hormonal Changes and Diabetes - It can be a bumpy ride!
Page 44: Hormonal Changes and Diabetes - It can be a bumpy ride!

Low testosterone levels associated with lower survival rates

Traish, Am J Med 2011

Page 45: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 46: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 47: Hormonal Changes and Diabetes - It can be a bumpy ride!

Testosterone replacement

• Needs to be followed carefully – Testosterone levels – Hematocrit – PSA – Clinical response

• Relief of symptoms • Bone health • Metabolic syndrome

Page 48: Hormonal Changes and Diabetes - It can be a bumpy ride!

Goals of treatment

• Relief of symptoms • Bone health • ?improvement in metabolic syndrome

Page 49: Hormonal Changes and Diabetes - It can be a bumpy ride!

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….

Page 50: Hormonal Changes and Diabetes - It can be a bumpy ride!

Menopause and Diabetes

Page 51: Hormonal Changes and Diabetes - It can be a bumpy ride!

Definition of menopause

• Perimenopause – Irregular menses – cycle length variation of

more than 7 days from usual • Menopause

– 12 months of amenorrhea

Page 52: Hormonal Changes and Diabetes - It can be a bumpy ride!

Symptoms of menopause

• Vasomotor • Vaginal dryness • Urinary incontinence • Sleep disturbance

Page 53: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 54: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 55: Hormonal Changes and Diabetes - It can be a bumpy ride!

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

Page 56: Hormonal Changes and Diabetes - It can be a bumpy ride!

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