UPDATE IN DIAGNOSIS AND MANAGEMENT GESTATIONAL DIABETES KALTHOM ABDUL AZIZ.

UPDATE IN DIAGNOSIS AND MANAGEMENT

GESTATIONAL DIABETES

KALTHOM ABDUL AZIZ

• 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

OBJECTIVES

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

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Gestational Age (weeks)

Normal pregnancy

Brief overviewBrief overview

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Gestational Age (weeks)

Gestational diabetes


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

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

DEPENDS ON WHO YOU ASK!!

CURRENT RECOMMENDATIONS FOR

SCREENING FOR GDM

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 Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. Mellitus on Pregnancy Outcomes.

OutcomeOutcome InterventioIntervention Groupn Group

Routine-Routine-Care Care GroupGroup

Adjusted P Adjusted P valuevalue

InfantsInfants

Total Number 506 524

Serious perinatal complications

7 (1%) 23 (4%) 0.04

WomenWomen

Total Number 490 510

Labor induction 189 (39%) 150 (29%) <0.001

Cesarean delivery

152 (31%) 164 (32%) 0.73

• 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

Conclusions

• 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

Hyperglycemia and Adverse Pregnancy Hyperglycemia and Adverse Pregnancy Outcomes (HAPO). NEJM, May, 2008.Outcomes (HAPO). NEJM, May, 2008.

Conclusions

• 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)

Goals and surveillance

• 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 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

MNT and physical activity

• 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

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


• 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• 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


• 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• 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• 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• 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• 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


• 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

Post partum/long term

• 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

Conclusions

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

Measure of glycemia Threshold

Fasting glucose > 126 mg/dl

A1C > 6.5%

Random glucose > 200 mg/dl

To diagnose overt diabetes (preexisting) in pregnancy

Summary

International Association of Diabetes and Pregnancy Study

Groups, 2009

SUMMARY

Glucose measure Glucose threshold

FPG 92 mg/dl

1-hr plasma glucose

180 mg/dl

2-hr plasma glucose

153 mg/dl

Diagnosis of GDM (75-g OGTT)

*One or more of these values must be met or exceeded for diagnosis of GDM


Groups, 2009

SUMMARY

• First prenatal visit• 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


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-hr2-hr <90<90 91-91-108108

109-109-125125

126-126-139139

140-140-157157

158-158-177177

>178>178

1-hr1-hr <105<105 106-106-132132

133-133-155155

156-156-171171

172-172-193193

194-194-211211

>212>212

FBSFBS <75<75 75-7975-79 80-8480-84 85-8985-89 90-9490-94 95-9995-99 >100>100

11 22 33 44 55 66 77

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 PurposePost-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 75-g 2-h OGTT Assess glucose metabolism

Annually Fasting plasma glucose Assess glucose metabolism

Tri-annually 75-g 2-h OGTT Assess glucose metabolism

Prepregnancy 75-g 2-h OGTT Assess glucose metabolism

Metabolic assessments after GDM

5th Annual Workshop-Conference on GDM

THANK YOU

UPDATE IN DIAGNOSIS AND MANAGEMENT GESTATIONAL DIABETES KALTHOM ABDUL AZIZ.

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