Update in Diagnosis and Management Gestational Diabetes Update in Diagnosis and Management KALTHOM ABDUL AZIZ
Objectives Review basic physiology of gestational diabetes Review fetal and maternal implications Review current recommendations for screening for GDM Review 3 important studies published within last 5 years that are driving current recommendations Review recommendations from the 5th International Workshop-Conference on Gestational Diabetes Mellitus Review use of insulin analogs in pregnancy Review use of oral antihyperglycemic agents in pregnancy
Brief overview Defined as carbohydrate intolerance that begins or is first recognized during pregnancy Important because it impacts maternal health care both during and after pregnancy Incidence varies, but most often reported as 5-7% of pregnant women; may be greater in some high-risk populations
Brief overview Insulin Resistance Insulin Output Normal pregnancy 12 24 36 Gestational Age (weeks)
Brief overview Insulin Resistance Insulin Output Gestational diabetes 12 24 36 Gestational Age (weeks)
Brief overview Underlying risk factors include increased maternal age, obesity, h/o GDM in prior pregnancy, h/o large babies Increased risk for development of hypertensive disorders, cesarean delivery, and developing diabetes later in life
Brief overview Pederson Hypothesis (1952) Maternal hyperglycemia Fetal hyperglycemia Fetal hyperinsulinemia Pederson Hypothesis (1952)
Brief overview Fetal risks include adverse events related to macrosomia, ie, shoulder dystocia and birth injuries, neonatal hypoglycemia and hyperbilirubinemia As rates of obesity increase, so do the rates of type 2 diabetes and GDM
Current recommendations for screening for GDM Depends on who you ask!!
Patients of intermediate risk should be screened at 24 to 28 weeks Recommended screening is 2-step approach, with 50-g 1-hr GCT followed by 2-hr or 3-hr 100-g OGTT Threshold value for 1-hr GCT is 130 or 140 – either is acceptable Threshold values for 3-hr OGTT are 95, 180, 155, 140, respectively; 2 values must be abnormal to diagnose GDM
WHO advocates universal screening utilizing a one-step 2-hr 75-g OGTT Patient is diagnosed with GDM if fasting > 126 or 2-hr > 140
Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. Intervention Group Routine-Care Group Adjusted P value Infants Total Number 506 524 Serious perinatal complications 7 (1%) 23 (4%) 0.04 Women Total Number 490 510 Labor induction 189 (39%) 150 (29%) <0.001 Cesarean delivery 152 (31%) 164 (32%) 0.73
Number needed to treat to prevent serious complication was 34 Conclusions Treatment of women with GDM (glucose intolerance) reduced the rate of serious perinatal complications from 4% to 1% Number needed to treat to prevent serious complication was 34 Benefits were associated with increased rate of labor induction, but not an increased rate of C/S
Hyperglycemia and Adverse Pregnancy Outcomes (HAPO). NEJM, May, 2008. With increasing maternal glucose levels, the frequency of each primary outcome increased, although less so for clinical neonatal hypoglycemia than for the others Secondary outcomes of preeclampsia, shoulder dystocia or birth injury, premature delivery, NICU admit, and hyperbilirubinemia also showed significant positive associations with maternal glycemia Conclusions
Goals and surveillance Maternal glycemia Target glucose concentrations: FBS < 96 1 hr PP < 140 2 hr PP < 120 Daily SMBG using meters appears to be superior to less frequent monitoring in the clinic
Goals and surveillance Assessment of fetal response utilizing ultrasound measurements, particularly of fetal abdomen, in second and early third trimesters can provide useful information Less intensified management may be allowed with normal growth (fetal AC < 75th percentile for GA)
MNT and physical activity Medical nutrition therapy remains cornerstone of treatment for GDM; however, relatively little information available to allow evidence-based recommendations regarding specific nutritional approaches such as total calories and nutrient distribution to the management of GDM
MNT best prescribed by registered dietician MNT and physical activity MNT best prescribed by registered dietician Food plans should be culturally appropriate Adjust amount and type of carbohydrate to achieve target for PP glucose concentrations No data on optimal weight gain for women with GDM Physical activity of 30 min/day is recommended for individuals capable of participating
Intensified medical therapy Insulin remains cornerstone in treatment of patients who fail to maintain glycemic goals with MNT Insulin analogs offer advantages of improved glucose control with immunogenic rates similar to human insulin
Rapid-acting insulin analogs (RAIA) Intensified medical therapy Rapid-acting insulin analogs (RAIA) Lispro (Humalog) and Aspart (Novolog) Achieve more rapid insulin peak and have been shown to provide better post-prandial glucose control Multiple studies have demonstrated improved PP glucose control with RAIA vs human regular insulin with no increased risk of complications, such as retinopathy or teratogenic effect
Intensified medical therapy Long-acting insulin analogs Glargine (Lantus) and Detemir (Levomir) Lantus provides peak-less duration of action around 24 hrs, translating to less glucose variability and lower risk of nocturnal hypoglycemia Levomir also with peak-less but less longer duration of action, about 12 hrs; provides similar benefits as Lantus
Long-acting insulin analogs: safety Intensified medical therapy Long-acting insulin analogs: safety Currently classified as Category C by FDA Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus. Compares to NPH which is Category B and is onlybasal insulin that has received FDA approval for treating GDM specifically Review article Nov 2007: “long-acting insulin analogs do not yet have sufficient safety evaluation in clinical studies to warrant their use during pregnancy” Recent placental perfusion study published in Mar 2010 showed Lantus does not cross the human placenta
Intensified medical therapy Oral antihyperglycemic agents Glyburide acts by promoting production of insulin in the pancreas Langer, et al. NEJM 2000: Randomized, prospective study comparing glyburide and insulin in women with GDM Conclusion: In women with GDM, glyburide is a clinically effective alternative to insulin therapy.
Oral antihyperglycemic agents Intensified medical therapy Oral antihyperglycemic agents Metformin is thought to act by inhibiting liver’s production of glucose; appears to increase insulin sensitivity/reduce insulin resistance Rowan, et al. NEJM 2008: Randomized, prospective study comparing metformin and insulin in GDM Conclusion: In women with GDM, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment.
Fetal surveillance Obstetric management Ultrasound screening for congenital anomalies recommended for women with GDM who present with A1C > 7.0% or FPG > 120 Data insufficient to determine whether surveillance beyond self-monitoring of fetal movements is indicated in women with GDM who continue to meet targets of glycemic control with MNT regimens alone and in whom fetal growth is normal
Obstetric management Maternal surveillance Risk for PTD may be increased with untreated GDM Use of steroids to enhance fetal lung maturity should not be withheld because of GDM but intensified monitoring of glucose levels is indicated with possible need for (increased) insulin Risk for hypertensive disorders increased with GDM Blood glucose monitoring should be continued during labor with insulin or glyburide as necessary to correct maternal hyperglycemia
Timing and route of delivery Obstetric management Timing and route of delivery No data supporting delivery of women with GDM prior to 38 weeks in absence of objective evidence of maternal or fetal compromise Lung maturity amnio not indicated in well-controlled patients who have indications for induction or C/S as long as reasonable certainty of dates
Timing and route of delivery Obstetric management Timing and route of delivery Delivery of LGA fetus in setting of GDM is associated with increased risk of birth injury compared with nondiabetic population Strategies to reduce this risk include liberal policy toward C/S; however, no controlled trials available to support this approach
Post partum/long term Studies show that after GDM, 35-60% of women develop Type 2 diabetes within 10 years Glucose tolerance testing should be performed 6-12 weeks after delivery in GDM women who do not have diabetes immediately PP Optimal testing frequency for diabetes long term has not been established
Conclusions Although treatment of mild GDM did not reduce the frequency of the composite primary outcome, it did lower the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and preeclampsia
Summary Screening/diagnosis No new guidelines at present WHO endorses universal screening with single step, arguing that the 2-step process introduces additional barrier to care Discussions continue around use of fasting, random glucose, or A1C at initial visit, but no consensus at present
Summary Measure of glycemia Threshold Fasting glucose > 126 mg/dl To diagnose overt diabetes (preexisting) in pregnancy Measure of glycemia Threshold Fasting glucose > 126 mg/dl A1C > 6.5% Random glucose > 200 mg/dl International Association of Diabetes and Pregnancy Study Groups, 2009
Summary Glucose measure Glucose threshold FPG 92 mg/dl Diagnosis of GDM (75-g OGTT) Glucose measure Glucose threshold FPG 92 mg/dl 1-hr plasma glucose 180 mg/dl 2-hr plasma glucose 153 mg/dl *One or more of these values must be met or exceeded for diagnosis of GDM International Association of Diabetes and Pregnancy Study Groups, 2009
Summary First prenatal visit 24-28 weeks Measure FPG, A1C, or random glucose on all or only high-risk women If results indicate overt diabetes as per Table 1, treat and f/u as for preexisting diabetes If results are not diagnostic of overt diabetes and FPG > 92 but < 126, diagnose as GDM; if FPG < 92, test for GDM at 24-28 weeks 24-28 weeks 2-hr 75-g OGTT after overnight fast on all women not previously found to have overt diabetes or GDM Overt diabetes if FPG > 126 GDM if one or more values equals or exceeds thresholds Normal if all values on OGTT less than thresholds International Association of Diabetes and Pregnancy Study Groups, 2009
Summary Medical management of GDM includes following: Nutritional therapy Exercise Self-monitoring of glucose at home If diet and exercise fail, oral hyperglycemic agent or insulin Glyburide “preferred” but metformin safe Short-acting insulin analogs should be standard, and long-acting analogs not far behind, if not already here Goal: Euglycemia!!
Summary 2-hr 1-hr FBS 1 2 3 4 5 6 7 <90 91-108 109-125 126-139 140-157 158-177 >178 1-hr <105 106-132 133-155 156-171 172-193 194-211 >212 FBS <75 75-79 80-84 85-89 90-94 95-99 >100 1 2 3 4 5 6 7
Summary Fetal surveillance with GDM Increased surveillance of fetal well-being suggested if oral agent or insulin necessary, or abnormal fetal growth evident on ultrasound Optimal timing of delivery remains uncertain, but would consider delivery by 39 weeks if evidence of poor glucose control and/or abnormal fetal growth noted Allow usual indications for delivery management if diet controlled with normal growth and well-being
Summary Postpartum management Assess fasting and/or 2-hr PP in first day or two after delivery – no further treatment necessary if normal (majority of GDM) If fasting and/or 2-hr PP abnormal, continue oral agent or insulin Screen for Type 2 diabetes at 6-week postpartum visit Council patients regarding dietary and behavioral changes necessary to minimize risk of developing overt diabetes later in life
Summary Time Test Purpose Post-delivery (1-3 d) Postpartum visit Metabolic assessments after GDM Time Test Purpose Post-delivery (1-3 d) Fasting or random glucose Detect persistent, overt diabetes Postpartum visit 75-g 2-h OGTT PP classification of glucose metabolism per ADA 1 year postpatum Assess glucose metabolism Annually Fasting plasma glucose Tri-annually Prepregnancy 5th Annual Workshop-Conference on GDM
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