Update in Diabetes and Pregnancy:

Bridging the Care Between Providers

Dr. Erin Keely

Chief, Division of Endocrinology and MetabolismThe Ottawa Hospital

Professor, Depts of Medicine and Obstetrics/GynecologyUniversity of Ottawa

Objectives:.At the end of this presentation I hope you will be

able to: Appreciate the importance of preconception

care for women with diabetes and obesity Recognize the similarities and differences

between type 1 and type 2 diabetes in pregnancy

Identify new GDM diagnostic guidelines may be coming

Appreciate the importance of the “fourth trimester” for women with gestational diabetes

Classification of Diabetes

Pre-gestational Type 1 Type 2

Gestational

other

What’s the difference between type 1 and 2 for pregnancy?

Comorbidities type 1 - autoimmunity, 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

Confidential Enquiry into Maternal and Child Health (2002-2004)

Type 1(n=2767)

Type2(n=1401)

Incidence 0.38% 0.10%

% Caucasian 91.3% 51.2%

Median age at delivery (yrs)

30.0 33.5

Prepregnancy counselling documented

38% 25%

Prepregnancy glycemic test recorded

40% 29%

Folic acid 42.9% 29.4%

Preconception care in managed care setting

Women 18-45 yrs enrolled in TRIAD study Asked to recall if had discussions about

glycemic control before conception and use of family planning

52% of women recalled discussions about preconception glucose control, 37% recalled family planning advice

Patient age (OR 0.91, CI 0.86-0.96) and BMI (OR 0.96, CI 0.93-0.99) predicted glucose control counselling

Younger age and lower BMI more likely to receive counsellingYounger age and lower BMI more likely to receive counselling

Kim, Am J Obstet Gynecol, 2005

Women’s perceptions on becoming pregnant

n=15, type 1 Intention of becoming pregnant is a continuum

Not planned/unplanned; wanted/unwanted; Use term ?readiness

Some women felt anxious after formal prepregnancy planning sessions

Conclusions Advice must be tailored to each women’s current

situation Build on the patients resources Health professionals normally seeing women in relation

to their diabetes may be the best

Griffiths, British J of General Practice, 2008

Personal experiences of those who don’t come for prepregnancy care n=29 (21 type 1, 8 type 2) Semi-structured interviews Reasons for not attending pre-

pregnancy care Got pregnant quicker than expected (45%) Fertility concerns (31%) Negative relationships with providers

(21%) Fear of disappointment, wanting

pregnancy to be normal (17%) Logistics/finances (10%)

Murphy, Diab Medicine 2010;27:92-100Murphy, Diab Medicine 2010;27:92-100

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?

Type 2 diabetes is at least as severe as type 1 diabetes

Obstetrical risks and obesity Infertility Failure of

contraception Gestational or type 2

diabetes Preeclampsia Risk of c-section Surgical complications

Wound Respiratory Thrombosis anaesthesia

First trimester loss Late pregnancy loss Macrosomia Congenital anomalies

Neural tube Cardiac More difficult to

diagnose Decreased breast

feeding Longterm maternal and

childhood obesity

Treatment of type 2 diabetes may result in conception

-metformin and glitazones are potent fertility treatments

Is your patient ready to conceive?

Diabetes and Congenital Anomalies

Hyperglycemia

Obesity

Medications

Glucose is a teratogen

Sacral agenesis

+ve pregnancy test MD appt

The first prenatal visit is months too late!

Target: A1c < 0.07

HgbA1c and Congenital Anomalies

Poor pregnancy outcome in women with type 2 diabetes

61 women with type 2 vs. 240 with type 1 from 1996-2001

type 2type 1

Perinatal mortality 6.7% vs 1.7% Cong anomalies 6.7% vs 1.7% HgbA1c 6.8% vs 7.0%

Clausen et al, Diab Care 2005;28:323-328

Maybe it isn’t just the glucoseMaybe it isn’t just the glucose

Increased risk of congenital anomalies and obesity

Many studies support increased risk

Population based case-control, Metropolitan Atlanta Congenital Defects program

Overweight (BMI 25.0-29.9) Cardiac 2.0 (1.2-3.1) Multiple anomalies 1.9 (1.1-3.4)

Obese (BMI ≥ 30) Spina bifida OR 3.5 (1.2-10.3) Omphalocele 3.3 (1.0-10.3) Cardiac 2.0 (1.2-3.4) Multiple anomalies 2.0 (1.0-3.8)

Watkins et al., Pediatrics 2003Watkins et al., Pediatrics 2003

20

For every 1 increase in BMI (kg/m2),

the risk of a neural tube defect

increases 7%

Watkins, Pediatrics 2003

The epidemic of obesity may be leading to an epidemic of birth defects

The epidemic of obesity may be leading to an epidemic of birth defects

Will more folate help?

Folate levels have decreased 16% since fortification of cereal (NHANES data)

MMWR weekly Jan 5, 2007

NTD increased 1.2 fold per 10 kg maternal weight even after fortification

Ray, Am J Obstet Gynecol 2005

Obese women less likely to eat cereals, vegetables Laraia, Public Health Nutr 2007

Obese women have lower serum folate levels with same intake – need to take an additional 350 ug/day

Mojtabai, Eur J Epidemiol 2004

Recommendation

Benefit of >0.4 mg folate supplementation has not been studied

ACOG Committee Opinion, Obstet Gynecol 2005

5 mg folate replacement preconception for all women with BMI>35, women with diabetes

Wilson, JOGC 2007; CDA Clinical Practice Guidelines, 2008

ACE inhibitor exposure in pregnancy

Bowen, Am J Obstet Gynecol 2008

Risk of Congenital anomalies and ACEI

Any (n=18)

2.71 RR (1.72-4.27)

CV (n=7) 3.72 RR (1.89-7.30)

CNS (n=3) 4.39 RR (1.37-14.02)

Cooper, NEJM 2006

Treatment of dyslipidemiaTreatment of dyslipidemia

Statins Limited and conflicting data No evidence of harm, but no evidence

of benefit

Fibrates (PPAR agonists) Clearly cross placenta Only in severe hypertriglyceridemia

Oral hypoglycemics for type 2 diabetes in pregnancy

Glyburide• don’t cross placenta• Likely safe, but ineffective in T2DM

Metformin• crosses placenta• Possible benefit in first trimester

Glitazones• Cross placenta especially after 10 weeks• Limited safety data

Change to insulin prepregnancy unless using metformin for ovulation induction

Diabetes complications Microvascular

retinopathy nephropathy neuropathy

macrovascular coronary artery disease cerebrovascular disease peripheral vascular disease

Retinopathy

most studies suggest worsening

laser before pregnancy - stable for 6 months

Nephropathy Normally increase GFR 50% in pregnancy

may not be able to increase GFR, GFR may decline

Will increase Uprotein excretion

If serum creatinine >125 umol/L risk of permanent/prolonged worsening

High risk of superimposed pre-eclampsia

Infections

Increased antepartum urinary, respiratory asymptomatic bacturia should be

treated

increased postpartum c-section incision mastitis

Effects on glycemic control Marked increase in insulin resistance

Due to placental effect - GOOD thing increase in cortisol, prolactin, hPL

insulin dosages increase 2-3 fold

Increased risk of unrecognized hypoglycemia Especially first trimester Risk of seizures, LOC

Increased risk of diabetic ketoacidosis (T1) high fetal mortality Can be precipitated by steroids for lung maturity

1st Trimester issues

Glycemic control HBGM qid premeal 4-6 mmol/L, 2 hr pc < 8 hypoglycemia symptoms

review diet/ hyperemesis reassess complications accurate dating of pregnancy

(ultrasound)

2nd trimester issues

Glycemic control insulin requirements start to increase

complications watch BP, repeat urine, reinforce

need for ophthamology FU fetal assessment

level 2 and cardiac echo

3rd trimester issues

Glycemic control

complications worsening

hypertension/superimposed pre-eclampsia

fetal assessments

As the placenta matures a decrease in insulin requirements starts to occur around 38 weeks gestation

Decrease in the mother’s insulin requirements after delivery of the placenta makes the first postpartum day a high risk period for hypoglycemia

Labour and delivery and postpartum

Neonatal hypoglycemia is positively correlated with maternal plasma glucose at delivery

Study found no cases of neonatal

hypoglycemia if the maternal plasma glucose at delivery was <7.1 mmol/L.

Acta paediatri Scand 74:268-273, 1985

Study found no relation between neonatal glucose and maternal glucose until maternal glucose > 9 mmol/L.

ACOG 99;4:537-541, 2002

Neonatal hypoglycemia dependent on maternal glucose at delivery

Consistency in peripartum insulin orders may be difficult due to multiple caregivers at different levels of training

If not done consistently may be completed by someone not familiar with patient’s glucose control, insulin management and preference for self-care

Appropriate regimens may not be instituted for safe postpartum management

Peripartum insulin orders

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

Gestational Diabetes

Carbohydrate intolerance with onset or first recognition in pregnancy

2-4% of pregnancies

Same risk factors as type 2 diabetes

Multinational U.S. centred observational study Designed to clarify the risk 75 gram OGTT 24-32 weeks GA

Excluded if FBS > 5.8 or 2 hr > 11.1 Remainder of the women were observed

No Rx, standard of care for delivery

HAPO > 23 000 women FBS 4.5 mmol/l 1hr GTT 7.4 mmol/l 2hr GTT 6.2 mmol/l

1° outcomes BW > 90%, 1° C/S, neonatal hypoglycemia, fetal

hyperinsulinemia (cord c-peptide levels)

2 °outcomes Preterm birth < 37 wks, birth injury, NICU, ↑

bilirubin, preeclampsia

What we would consider quite normal!

HAPO, N Engl J Med 2008; 358:1991-2002HAPO, N Engl J Med 2008; 358:1991-2002

HAPO

Perinatal risk increases in linear fashion even within a fairly normal range of glucose values

association between glucose and adverse outcomes occurs even within limits not previously thought to be problematic or diagnostic for GDM

IADPSG Proposed New Diagnostic Criteria

Diabetes Care March 2010Diabetes Care March 2010

First prenatal visit measure FPG, A1C or random glucose on all or high-risk women

diagnose overt diabetes in pregnancy if: Fasting ≥ 7.0 mmol/l A1c ≥ 6.5% Random plasma glucose ≥ 11.1 mmol/l

(+confirmation)

Diagnose GDM if FPG 5.1- 6.9 mmol/l

If FPG < 5.1 mmol/l, retest at 24-28 wks

IADPSG Proposed New Diagnostic Criteria

Diabetes Care March 2010Diabetes Care March 2010

At 24-28 weeks 75 g OGTT

No 50 g screen

only 1 abnormal value required

cut-offs Fasting 5.1 mmol/L (5.3) 1hr 10.0 mmol/L

(10.6) 2hr 8.5 mmol/L

(8.9)

Reasons to look for GDM

index pregnancy macrosomia hypoglycemia in neonate fetal loss

offspring type 2 dm obesity

maternal - type 2 dm

Bottom Line for treatment Diet Home blood glucose monitoring

Target fasting 3.8-5.2 mmol/l 1 hr pc 5.5-7.7 mmol/l 2 hr pc 5.0-6.6 mmol/l

Insulin first Oral agents second

Glyburide More effective Concern of long term consequences has limited use

Metformin Likely safe despite crossing placenta Less effective

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

1. As women who have had GDM are defined as high risk of developing subsequent type 2 diabetes, they should be re-evaluated postpartum [Grade D, Consensus].

A 75-g OGTT should be performed between 6 weeks and 6 months postpartum to establish their glucose status.

Women who are suspected of having had pre-existing diabetes should be monitored more closely postpartum.

All women with GDM should be counselled on a healthy lifestyle.

2008 clinical practice guidelines

2 hr GTT vs. fasting glucose only

DM 4/99 (4%)

IGT 17/99 (17%)

IFG 11/99 (11%)

1 yr post partum in Ottawa

Why pick up people at risk for type 2 diabetes?

The next pregnancy (interpartum not postpartum)

Prevention of progression to type 2 diabetes

Lifestyle and pharmacological approaches shown to be effective

Diabetes Prevention Program intensive lifestyle intervention and metformin reduced

incidence of T2DM by 50% (Ratner, JCEM 2008)

Postpartum period critical for changing behaviours Potential impact on whole family

Rates of postpartum testing 25-56% of women screened

6 wks-6 mths postpartum (Hunt Curr Diab Rep 2010;10:235-241)

GTT in Ottawa, usual care 2000 0% 2005 14% 2009 14%

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

Chronic Disease in Canada, 2011Chronic Disease in Canada, 2011

Risk perceptionN=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;2:107-10Malcolm, Obstetric Medicine 2009;2:107-10

Who should provide pp screening?

MDs (n=170)

Patients (n=136)

PCP 65% 76%

Obstetrician 12% 9%

Internist 9% 12%

So, how can we do better

Admit defeat, simplify and just ask for fasting glucose NO

Diabetes providers take ownership ?see everyone back postpartum Not in my institution

Need to improve communication

With patientWith patient Consistent, repetitive, writtenConsistent, repetitive, written Link to baby healthLink to baby health

““by the time your baby has their 6 month by the time your baby has their 6 month needle, you should have had your sugar needle, you should have had your sugar checked”checked”

RemindersRemindersWith providersWith providers

Reduce fragmentation of careReduce fragmentation of care Obstetricians, family doctors, midwives, public Obstetricians, family doctors, midwives, public

health, pharmacists etchealth, pharmacists etcBetween medical recordsBetween medical records

Role of discharge summaries, electronic health Role of discharge summaries, electronic health records, diabetes registriesrecords, diabetes registries

Breastfeeding and GDM

Additional benefits of breastfeeding to women with GDM

Less postpartum weight retention Less maternal diabetes, metabolic syndrome Less offspring obesity and diabetes

Gunderson Obstet Gynecol 2007Gunderson Diabetes 2010

Harder for women with diabetes/obesity to breastfeed

Difficulties with infant latching Delayed arrival of milk

Lower prolactin levels Increased obstetrical complications including operative delivery Body image discomfort

Gundarson, Diabetes Care, 2011Gundarson, Diabetes Care, 2011

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%)

90% intend to breastfeed Approximately 50% leave hospital exclusively breastfeeding

Source: BORN Ontario (Niday Perinatal Database)Source: BORN Ontario (Niday Perinatal Database)

Summary Women with type 1 and type 2 diabetes

are at increased obstetrical risk Preconception care essential for

improved outcomes Gestational diabetes diagnostic criteria

may be changing Increased emphasis on working

together across continuum to ensure better preconception, antepartum, postpartum and interpartum care