diabetes in pregnancy ass. pro. : s. rouholamin
DESCRIPTION
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 pregancyTRANSCRIPT
Diabetes in Pregnancy
Ass. Pro. : S. Rouholamin
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
Gestational Diabetes Mellitus
Gestational Diabetes• Reduced sensitivity to insulin in
2nd and 3rd trimesters• “Diabetogenic State” when insulin
production doesn’t meet with increased insulin resistance
Hod and Yogev Diabetes Care 30:S180-S187, 2007Crowther, et al NEJM 352:2477–2486, 2005 Langer, et al Am J Obstet Gynecol 192:989–997, 2005
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 30:S180-S187, 2007Crowther, et al NEJM 352:2477–2486, 2005 Langer, et al Am J Obstet Gynecol 192:989–997, 2005
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 192:1768–1776, 2005Diabetes Care 31(S1) 2008 Diabetes Care 25:1862-1868, 2002
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
Gestational Diabetes-Screening
• Screen all very high risk and high risk
• Very high risk: Previous GDM, strong FH, previous infant >9lbs
• High risk: Those not in very high risk or low risk category
Gestational Diabetes-Screening
• Low Risk (all of following)• Age <25 years• Weight normal before pregnancy• Member of an ethnic group with a
low prevalence of diabetes
Diabetes Care 31(S1) 2008
• Low Risk (all of following)(cont’d)• No known diabetes in first-degree
relatives• No history of abnormal glucose
tolerance• No history of poor obstetrical outcome
Gestational Diabetes-Screening
Diabetes Care 31(S1) 2008
Gestational Diabetes Screening
• 2 step approach oral glucose tolerance test (OGTT)• 1) 50gm 1 hour OGTT
• 2) 100gm 2 hour OGTT
Gestational Diabetes-Screening
• GDM screening at 24–28 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
Gestational Diabetes-Screening• GDM screening at 24–28 weeks:
• Two-step approach (cont’d)
• 2) 3 hour OGTT* (100g glucose load) Fasting: >95 mg/dl (5.3 mmol/l)
1 h: >180 mg/dl (10.0 mmol/l)2 h: >155 mg/dl (8.6 mmol/l)3 h: >140 mg/dl (7.8 mmol/l)
*2 of 4 Diabetes Care 31(S1) 2008
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 30:S251-S260, 2007
Glucose Control in GDM• Preprandial: <95 mg/dl, and either:
1-h postmeal: <140 mg/dlor2-h postmeal: <120 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):B161–B167, 1998
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 GDMSummary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus Diabetes Care 30:S251-S260, 2007
Langer et al N Engl J Med 343:1134–1138, 2000
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
Gestational Diabetes-Management• Fasting, pre-meal, 2-hour post-
prandial blood glucose probably all important
• Mean blood glucose >105-115, greater perinatal mortality
• A1C in GDM probably not important Am J Obstet Gynecol 192:1768–1776, 2005
ADA Position StatementPettit, et al Diabetes Care 3:458–464, 1980 Karlsson, Kjellmer Am J Obstet Gynecol 112:213–220, 1972Langer, et al Am J Obstet Gynecol 159:1478–1483, 1988
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
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.
GDM Complications• Macrosomia • Fractures • Shoulder dystocia• Nerve palsies (Erb’s C5-6)• Neonatal hypoglycemia• Pregnancy outcomes can be very
poor with HTN/nephropathyGabbe, Obstetrics: Normal and Problem Pregnancies 2002
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 30:S225-S235, 2007
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
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
Diabetes in Pregnancy:Clinical implications
Fetal macrosomiaFetal macrosomia
Shoulder dystociaShoulder dystocia
Diabetes in Pregnancy: Clinical Implications
• Obstetric complications (cont’d.):– Preterm delivery– Intrauterine fetal demise– Traumatic delivery (e.g., shoulder dystocia)– Operative vaginal delivery
• vacuum-assisted• forceps-assisted
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
GDM: Risk factors• Maternal age >25 years• Body mass index >25 kg/m2
• Race/Ethnicity– Latina– Native American– South or East Asian, Pacific Island ancestry
• Personal/Family history of DM• History of macrosomia
GDM: Diagnosis• Fasting blood glucose >126mg/dL or
random blood glucose >200mg/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/dL1 hour 180 mg/dL 190 mg/dL2 hour 155 mg/dL 165 mg/dL3 hour 140 mg/dL 145 mg/dL
Management:Glycemic 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%
Management:Overview
• 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
Management: Glycemic Control
• Blood glucose goals during pregnancy – Fasting < 95mg/dL– 1-hr postprandial < 130-140mg/dL– 2-hr postprandial am < 120mg/dL– 2 am < 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
Management:Nutrition
• 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
Management:Subcutaneous 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
Management:Oral 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
Management Summary:Pregestational 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
Management Summary:Pregestational 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
Management Summary:GDM
• 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)
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
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
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
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 (>9 lb infant, possible GDM)
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
Case Study• 26 weeks, no problems, maybe slightly
large for dates• 12 lb weight gain• Went directly to 3 hour GTT (100g)
Case Study• FBG: 94 ( > 95)• 1 hour: 192 (>180)• 2 hour: 160 (>155)• 3 hour: 149 (>140)
• 3 of 4 values abnormal= GDM
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
Glucose Control in GDM• Preprandial: <95 mg/dl, and either:
1-h postmeal: <140 mg/dlor2-h postmeal: <120 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):B161–B167, 1998
Case Study• Returns one week later• Has been following meal plan
“90% of time”• Has walked 15 minutes 2 times• Has 4 FBG > 100• 6 other values above target
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
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
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
Gestational Diabetes Mellitus
Risk 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
Type 2 Diabetes Prevention• Lifestyle- over 50% reduction of future type
2 diabetes • Bariatric (Lap-Band-future preg?)- strong
consideration in BMI >40 or >35 with co-morbid conditions
• Future treatments/prevention- no current medication role, possible in future
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 31:1060-1079, 2008
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 31:899-904, 2008 Kitzmiller, et al Diabetes Care 31:1060-1079, 2008
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 31:899-904, 2008 Kitzmiller, et al Diabetes Care 31:1060-1079, 2008
• 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
Preconception Counseling
Lawrence, et al Diabetes Care 31:899-904, 2008 Kitzmiller, et al Diabetes Care 31:1060-1079, 2008
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
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
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
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