Diabetes in Pregnancy

1
Diabetes in Pregnancy

• Ass. Pro. S. Rouholamin

2
Objectives

• Discuss Gestational Diabetes Mellitus (GDM) and
  Treatment
• Recognize common problems of GDM in Pregnancy
• Discuss long term followup of Gestational
  Diabetes Mellitus (GDM)
• Discuss needs of pre-existing diabetes in pregancy

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Gestational Diabetes Mellitus
4
Gestational Diabetes

• Reduced sensitivity to insulin in 2nd and 3rd
  trimesters
• Diabetogenic State when insulin production
  doesnt meet with increased insulin resistance

Hod and Yogev Diabetes Care 30S180-S187,
2007 Crowther, et al NEJM 35224772486, 2005
Langer, et al Am J Obstet Gynecol 192989997,
2005
5
Gestational Diabetes

• Human placental lactogen, leptin, prolactin, and
  cortisol result in insulin resistance
• Lack of diagnosis and treatment-increased risk of
  perinatal morbidities

Hod and Yogev Diabetes Care 30S180-S187,
2007 Crowther, et al NEJM 35224772486, 2005
Langer, et al Am J Obstet Gynecol 192989997,
2005
6
Gestational Diabetes

• Occurs in 2-9 of pregnancies
• 135,000 cases in U.S. annually
• Management can include insulin (usually
  preferred, better efficacy) or sulfonylureas (in
  very select cases)

Am J Obstet Gynecol 19217681776, 2005 Diabetes
Care 31(S1) 2008 Diabetes Care 251862-1868,
2002
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Gestational Diabetes and Type 2 Diabetes Risk

• Gestational Diabetes should be considered a
  pre-diabetes condition
• Women with gestational diabetes have a 7-fold
  future risk of type 2 diabetes vs.women with
  normoglycemic pregnancy

Lancet, 2009, 373(9677) 1773-9
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Gestational Diabetes-Screening

• Screen all very high risk and high risk
• Very high risk Previous GDM, strong FH,
  previous infant gt9lbs
• High risk Those not in very high risk or low
  risk category

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Gestational Diabetes-Screening

• Low Risk (all of following)
• Age lt25 years
• Weight normal before pregnancy
• Member of an ethnic group with a low prevalence
  of diabetes

Diabetes Care 31(S1) 2008
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Gestational Diabetes-Screening

• Low Risk (all of following)(contd)
• No known diabetes in first-degree relatives
• No history of abnormal glucose tolerance
• No history of poor obstetrical outcome

Diabetes Care 31(S1) 2008
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Gestational Diabetes Screening

• 2 step approach
• oral glucose tolerance test (OGTT)
• 1) 50gm 1 hour OGTT
• 2) 100gm 2 hour OGTT

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Gestational Diabetes-Screening

• GDM screening at 2428 weeks
• Two-step approach
• 1) Initial screening plasma or serum glucose
• 1 h after a 50-g oral glucose load
• Glucose threshold
• 140 mg/dl identifies 80 of GDM
• 130 mg/dl identifies 90 of GDM

Diabetes Care 31(S1) 2008
13
Gestational Diabetes-Screening

• GDM screening at 2428 weeks
• Two-step approach (contd)
• 2) 3 hour OGTT
• (100g glucose load)
• Fasting gt95 mg/dl (5.3 mmol/l)1 h gt180
  mg/dl (10.0 mmol/l)2 h gt155 mg/dl (8.6
  mmol/l)3 h gt140 mg/dl (7.8 mmol/l)

2 of 4 Diabetes
Care 31(S1) 2008
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Gestational Diabetes Management

• Dietician
• Diabetes Educator
• Consider referral to Diabetologist or
  Endocrinologist
• Moderate Physical Activity 30 minutes daily when
  appropriate

Summary and Recommendations of the Fifth
International Workshop-Conference on Gestational
Diabetes Mellitus Diabetes Care 30S251-S260,
2007
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Glucose Control in GDM

• Preprandial lt95 mg/dl, and either
• 1-h postmeal lt140 mg/dl
• or
• 2-h postmeal lt120 mg/dl and Urine ketones
  negative

Summary and recommendations of the Fourth
International Workshop-Conference on Gestational
Diabetes Mellitus. The Organizing Committee.
Diabetes Care 21(2)B161B167, 1998
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Gestational Diabetes-Medications

• Patients who do not meet metabolic goals within
  one week or show signs of excessive fetal growth
• Insulin has been the usual first choice
• Sulfonylureas (glyburide) may be used in select
  patients
• Other diabetes medications not recommended in GDM

Summary and Recommendations of the Fifth
International Workshop-Conference on Gestational
Diabetes Mellitus Diabetes Care 30S251-S260,
2007 Langer et al N Engl J Med 34311341138,
2000
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Diabetes MedicationsInsulins-Safety

• Aspart, Lispro, NPH, R, Lispro protamine all
  Category B and used in pregnancy
• All other insulins Category C
• Human Insulins-Least Immunogenic
• Breastfeed-All insulins considered safe

Data from Package Inserts
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Gestational Diabetes-Management

• Fasting, pre-meal, 2-hour post-prandial blood
  glucose probably all important
• Mean blood glucose gt105-115, greater perinatal
  mortality
• A1C in GDM probably not important

Am J Obstet Gynecol 19217681776, 2005 ADA
Position Statement Pettit, et al Diabetes Care
3458464, 1980 Karlsson, Kjellmer Am J Obstet
Gynecol 112213220, 1972 Langer, et al Am J
Obstet Gynecol 15914781483, 1988
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Insulin Dosing-GDM

• Insulin dosing
• Can use usual weight based dosing (i.e., 0.5
  u/kg)
• Practical dosing can be to start 10 units
  NPH with evening meal
• Most will titrate to BID, with eventual addition
  of
• Regular or Rapid Acting BID

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Alternate Insulin Dosing in GDM

• Regular or rapid acting (lispro or aspart) with
  meals, NPH at bedtime
• NPH Regular or rapid acting in AM, regular or
  rapid acting at supper, NPH at bedtime
• Titrate insulin based on SBGM values, tested
  fasting, pre-meal, 2 hour post-meal, bedtime,
  occasional 3 AM.

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GDM Complications

• Macrosomia
• Fractures
• Shoulder dystocia
• Nerve palsies (Erbs C5-6)
• Neonatal hypoglycemia
• Pregnancy outcomes can be very poor with
  HTN/nephropathy

Gabbe, Obstetrics Normal and Problem
Pregnancies 2002
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Gestational Diabetes Post-natal

• Fasting glucose rechecked 6-12 weeks following
  delivery
• Every 6 months thereafter to be screened for type
  2 diabetes
• Higher risk of developing Type 2 Diabetes

Kitzmiller, et al Diabetes Care 30S225-S235,
2007
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Metabolic changes in pregnancy

• Lipid metabolism
• Increased lipolysis (preferential use of fat for
  fuel, in order to preserve glucose and protein)
• Glucose metabolism
• Decreased insulin sensitivity
• Increased insulin resistance

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Metabolic changes in pregnancy

• Increased insulin resistance
• Due to hormones secreted by the placenta that are
  diabetogenic
• Growth hormone
• Human placental lactogen
• Progesterone
• Corticotropin releasing hormone
• Transient maternal hyperglycemia occurs after
  meals because of increased insulin resistance

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Diabetes in PregnancyClinical implications
Shoulder dystocia
Fetal macrosomia
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Diabetes in Pregnancy Clinical Implications

• Obstetric complications (contd.)
• Preterm delivery
• Intrauterine fetal demise
• Traumatic delivery (e.g., shoulder dystocia)
• Operative vaginal delivery
• vacuum-assisted
• forceps-assisted

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Diabetes in Pregnancy Clinical Implications

• Fetal macrosomia
• Disproportionate amount of adipose tissue
  concentrated around shoulders and chest
• Respiratory distress syndrome
• Neonatal metabolic abnormalities
• Hypoglycemia
• Hyperbilirubinemia/jaundice
• Organomegaly
• Polycythemia
• Perinatal mortality
• Long term predisposition to childhood obesity and
  metabolic syndrome

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GDM Risk factors

• Maternal age gt25 years
• Body mass index gt25 kg/m2
• Race/Ethnicity
• Latina
• Native American
• South or East Asian, Pacific Island ancestry
• Personal/Family history of DM
• History of macrosomia

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GDM Diagnosis

• Fasting blood glucose gt126mg/dL or random
  blood glucose gt200mg/dL
• 100 gm 3-hour glucose tolerance test
• (GTT) with 2 or more abnormal values

Carpenter and Coustan National Diabetes and Data Group
Fasting 95 mg/dL 105 mg/dL
1 hour 180 mg/dL 190 mg/dL
2 hour 155 mg/dL 165 mg/dL
3 hour 140 mg/dL 145 mg/dL
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ManagementGlycemic control

• Glycosylated Hemoglobin A1C (Hgb A1C) level
  should be less than or equal to 6
• Levels between 5 and 6 are associated with fetal
  malformation rates comparable to those observed
  in normal pregnancies (2-3)
• Goal of normal or near-normal glycosylated
  hemoglobin (Hgb A1C) level for at least 3 months
  prior to conception
• Hgb A1C concentration near 10 is associated with
  fetal anomaly rate of 20-25

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ManagementOverview

• Nutrition therapy
• Home self glucose monitoring
• Medical therapy if glycemic control not achieved
  with diet/exercise
• Subcutaneous insulin
• Oral hypoglycemic agents (Glyburide, Metformin)
• Antenatal monitoring

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Management Glycemic Control

• Blood glucose goals during pregnancy
• Fasting lt 95mg/dL
• 1-hr postprandial lt 130-140mg/dL
• 2-hr postprandial am lt 120mg/dL
• 2 am lt 120mg/dL
• Nocturnal glucose level should not go below 60
  mg/dL
• Abnormal postprandial glucose measurements are
  more predictive of adverse outcomes than
  preprandial measurements

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ManagementNutrition

• Caloric requirements
• Normal body weight - 30-35 kcal/kg/day
• Distributed 10-20 at breakfast, 20-30 at lunch,
  30-40 at dinner, up to 30 for snacks (to avoid
  hypoglycemia)
• Caloric composition
• 40-50 from complex, high-fiber carbohydrates
• 20 from protein
• 30-40 from primarily unsaturated fats

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ManagementSubcutaneous Insulin Therapy

• Insulin requirements increase rapidly, especially
  from 28 to 32 weeks of gestation
• 1st trimester 0.7-0.8 U/kg/d
• 2nd trimester 0.8-1 U/kg/d
• 3rd trimester 0.9-1.2 U/kg/d

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ManagementOral Hypoglycemic Agents

• Glitazones (Avandia, Actos)
• Sensitize muscle and fat cells to accept insulin
  more readily
• Decrease insulin resistance
• Sulfonylureas
• Augment insulin release
• 1st generation
• Concentrated in the neonate ? hypoglycemia
• 2nd generation (Glyburide)
• Low transplacental transfer
• Biguanide (Metformin, aka Glucophage)
• Increases insulin sensitivity
• Crosses placenta

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Management SummaryPregestational Diabetes

• Referral to perinatologist and/or endocrinologist
• Multidisciplinary approach
• Regular visits with nutritionist
• Hgb A1C every trimester
• Fetal Echocardiogram
• Level II ultrasound
• Opthamologist
• Baseline kidney and liver function tests

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Management SummaryPregestational Diabetes

• Optimize glycemic control frequent insulin dose
  adjustments
• Type 1 often have insulin pump
• Type 2 subcutaneous insulin
• Fetal monitoring starting at 28-32 weeks,
  depending on glycemic control
• Ultrasound to assess growth at 36 weeks
• Delivery at 38-39 weeks

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Management SummaryGDM

• Begin with diet / walk after each meal
• If borderline/mild elevations, consider metformin
  (start at 500 mg daily)
• Counsel about increased PTD rates
• Unlikely pre-existing DM
• If elevations start out moderate to severe or
  metformin fails, proceed to subcutaneous insulin
  therapy
• NPH (long acting)
• Humalog/Novalog (short acting)

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Management Intrapartum

• Attention to labor pattern, as cephalopelvic
  disproportion may indicate fetal macrosomia
• Careful consideration before performing operative
  vaginal delivery
• Hourly blood glucose monitoring during active
  labor, with insulin drip if necessary
• Notify pediatrics if patient has poorly
  controlled blood sugars antepartum or intrapartum

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Management Postpartum

• For patients with pregestational diabetes, halve
  dose of insulin and continue to check blood
  glucose in immediate postpartum period
• For GDM patients who required insulin therapy
  (GDMA2), check fasting and postprandial blood
  sugars and treat with insulin as necessary
• For GDM patients who were diet controlled
  (GDMA1), no further monitoring nor therapy is
  necessary immediately postpartum

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Management Postpartum

• For all GDM patients, perform 75 gram 2-hour OGTT
  at 6 week postpartum visit to rule out
  pregestational diabetes
• Most common recommendation is for primary care
  physician to repeat
• 2-hour OGTT every three years

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Case Study

• 28 y/o caucasian female
• 2nd pregnancy
• 1st pregnancy at age 22, term male infant, 10 lbs
  2oz, normal delivery
• Thinks had high blood sugar
• Very high risk (gt9 lb infant, possible GDM)

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Case Study

• No other significant medical history No
  tobacco
• Physical Exam VS normal
• 5 2
• 210 lbs
• BMI 38.4
• Remainder consistent with 12 weeks
  gestation

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Case Study

• 26 weeks, no problems, maybe slightly large for
  dates
• 12 lb weight gain
• Went directly to 3 hour GTT (100g)

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Case Study

• FBG 94 ( gt 95)
• 1 hour 192 (gt180)
• 2 hour 160 (gt155)
• 3 hour 149 (gt140)
• 3 of 4 values abnormal GDM

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Case Study

• Referred to Diabetes Educator and Dietician
• SMBG FBG, pre-meal, 2 hour post-prandial, HS, 3
  am prn
• Meal Plan
• No contraindications to exercise, encouraged to
  walk 15 min/daily

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Glucose Control in GDM

• Preprandial lt95 mg/dl, and either
• 1-h postmeal lt140 mg/dl
• or
• 2-h postmeal lt120 mg/dl and Urine ketones
  negative

Summary and recommendations of the Fourth
International Workshop-Conference on Gestational
Diabetes Mellitus. The Organizing Committee.
Diabetes Care 21(2)B161B167, 1998
48
Case Study

• Returns one week later
• Has been following meal plan 90
  of time
• Has walked 15 minutes 2 times
• Has 4 FBG gt 100
• 6 other values above target

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Case Study

• Referred to Diabetes Educator for insulin
  start
• NPH 10 units, 3 units Insulin aspart BID
• Phone followup q 3 days
• Continues appropriate clinic appointments

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Case Study

• 1-2 SMBG values out of target 1st week
• 3 weeks later, FBG, 2 hour post lunch and 2 hour
  post supper elevated about 50 of time
• NPH increased in PM (or could move to HS),
  insulin aspart added at lunch (2 or 3 units) and
  increased at supper

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Case Study

• Normal vaginal delivery at 38 weeks
• 8lb 10oz healthy female infant
• Patients FBS day after delivery 90
• Enrolled in Diabetes Prevention Program
• Converted to type 2 diabetes 2 years later
• Had lap-band 4 years later

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Gestational Diabetes MellitusRisk of Type 2
Diabetes

• Meta analysis 20 studies 675,455 women
• 7-fold increase in risk of type 2 diabetes
  following gestational diabetes vs. normoglycemic
  pregnancy
• Post pregnancy surveillance important

Bellamy, L. et al. Lancet, 2009, 373(9677) 1773-9
53
Type 2 Diabetes Prevention

• Lifestyle- over 50 reduction of future type 2
  diabetes
• Bariatric (Lap-Band-future preg?)- strong
  consideration in BMI gt40 or gt35 with co-morbid
  conditions
• Future treatments/prevention- no current
  medication role, possible in future

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Pre-Existing Diabetes and Pregnancy

• Pre-conception counseling (Diabetes
  Educator and Dietician included)
• Recommended pre-conception A1C as close to
  normal (6.0) without signficant hypoglycemia
• More Type 2 patients in child bearing years
  (diagnosed at younger age)

Kitzmiller, et al Diabetes Care 311060-1079,
2008
55
Preconception Counseling

• Whenever possible, organize multidiscipline
  patient-centered team care for women with
  preexisting diabetes in preparation for
  pregnancy.
• Women with diabetes who are contemplating
  pregnancy should be evaluated and, if indicated,
  treated for diabetic nephropathy, neuropathy, and
  retinopathy, as well as cardiovascular disease
  (CVD), hypertension, dyslipidemia, depression,
  and thyroid disease. (Celiac?)

Lawrence, et al Diabetes Care 31899-904, 2008
Kitzmiller, et al Diabetes Care 311060-1079,
2008
56
Preconception Counseling

• Medication use should be evaluated before
  conception, since drugs commonly used to treat
  diabetes and its complications may be
  contraindicated or not recommended in pregnancy,
  including statins, ACE inhibitors, angiotensin II
  receptor blockers (ARBs), and most noninsulin
  therapies. Aspirin should also be stopped.
• Continue multidiscipline patient-centered team
  care throughout pregnancy and postpartum.

Lawrence, et al Diabetes Care 31899-904, 2008
Kitzmiller, et al Diabetes Care 311060-1079,
2008
57
Preconception Counseling

• Educate pregnant diabetic women about the strong
  benefits of
• Long-term CVD risk factor reduction
• Breastfeeding
• Effective family planning with good glycemic
  control before the next pregnancy

Lawrence, et al Diabetes Care 31899-904, 2008
Kitzmiller, et al Diabetes Care 311060-1079,
2008
58
Pre-existing Type 2 Diabetes Pregnancy

• Oral agents are not used in pre-existing type 2
  diabetes in pregnancy
• Convert to insulin, similar to GDM
  insulin dosing

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Pre-existing Type 2 Diabetes Pregnancy

• If already on insulin, continue
• Insulin needs increase as pregnancy progresses
• Controversy Switch glargine or detemir to NPH?
• Continue lispro, aspart, or R if using

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Pre-existing Type 1 Diabetes and Pregnancy

• All continue on insulin
• Controversy glargine or detemir converted to
  NPH?
• Continue Regular/Rapid Acting
• If on pump, continue

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Summary

• Start insulin if not meeting goals after one week
  in GDM
• Pre-existing type 2, convert to insulin
• Pre-existing type 1, continue insulin
• Meet targets, avoid hypoglycemia