Presentation on theme: "Gestational diabetes mellitus"— Presentation transcript:
1 Gestational diabetes mellitus Dr. Kanakamani Madhivanan, M.D., D.M. (Endocrinology),Assistant ProfessorDepartment of Endocrinology, Diabetes, MetabolismChristian Medical College, Vellore
2 Plan of presentation Introduction Physiology of fuel metabolism in normal pregnancyPathophysiology of GDMEpidemiology of GDMScreening and diagnosisMaternal and fetal risksManagement of GDMObstetric management
4 Introduction Global increase in prevalence of DM Individual importance - Hyperglycemia in pregnancy has adverse effects on both mother and fetusPublic health importance – rising epidemic of DM in part attributed to the diabetic pregnanciesPrevention of type 2 DM should start intrauterine and continue throughout life
5 IntroductionGestational diabetes (GDM) is defined as any degree of impaired glucose tolerance of with onset or first recognition during pregnancy .Many are denovo pregnancy inducedSome are type 2 ( 35-40%)10% have antibodies
6 IntroductionDifficult to distinguish pregestational Type 2 DM and denovo GDMFasting hyperglycemiablood glucose greater than 180 mg/dL on OGTacanthosis nicgransHbA1C > 5.3%a systolic BP > 110 mm HgBMI > 30 kg/m2Fetal anomaliesClues for Type 1LeanDKA during pregnancySevere hyperglycemia with large doses of insulin
8 Fuel metabolism in pregnancy Goal is uninterrupted nutrient supply to fetusThe metabolic goals of pregnancy are1) in early pregnancy to develop anabolic stores to meet metabolic demands in late pregnancy2) in late pregnancy to provide fuels for fetal growth and energy needs.
9 Glucose metabolism in pregnancy Early pregnancyE2/PRL stimulates b cells –Insulin sensitivity same and peripheral glucose utilisation – 10% fall in BG levelsLate pregnancyFetoplacental unit extracts glucose and aminoacids, fat is used mainly for fuel metabolismInsulin sensitivity decreases progressively upto 50-80% during the third trimestervariety of hormones secreted by the placenta, especially hPL and placental growth hormone variant, cortisol, PRL,E2 and Prog
10 Glucose metabolism in pregnancy FASTINGaccelerated starvation and esxaggerated ketosis(maternal hypoglycemia, hypoinsulinemia, hyperlipidemia, and hyperketonemia)FEDhyperglycemia, hyperinsulinemia, hyperlipidemia, and reduced tissue sensitivity to insulinFatHyperinsulinemiaInsulin resistanceGlucoseAminoacidsFetus
11 24-hour insulin requirement before conception is approximately 0 24-hour insulin requirement before conception is approximately 0.8 units / kg.In the first trimester, the insulin requirement rises to 0.7units / kg of the pregnant weight – more unstable glycemia with a tendency to low fasting plasma glucose and high postprandial excursions and the occurrence of nocturnal hypoglycemiaBy the second trimester, the insulin requirement is 0.8 units per kilogram. From 24th month onwards steady increase in insulin requirement and glycemia stabilisesBy third trimester the insulin requirement is unit /kg pregnant weight per dayLast month – may be a decrease in insulin and hypoglycemias esp. nocturnal
13 Magnitude of problem: Global Prevalence of GDM varies worldwide and among different racial and ethnic groups within a countryAmerica – white women (3.9%) and Asian (8.7%)Europe – 0.6% to 3.6%Australia – 3.6% to 4.7% (Indian women – 17.7%)China – 2.3%; Japan – 2.9%Variability is partly because of the different criteria and screening regimens
14 Magnitude of the problem - India Chennai, hospital based, universal screening – 18.9% had FPG ≥ 126 and PPPG ≥ 140.Trivandrum – 15%Bangalore – 12%Erode – 18.8%Chennai, community based, universal screning, 17.8% in urban, 13.8% in semi urban and 9.9% in rural areas.Chennai : 0.56%Mysore Parthenon Study: 6%Maharashtra, hospital based, selective screening – 7.7% had GDM; 13.9% had IGGT.
15 Risk factorsA family history of diabetes, especially in first degree relativesPrepregnancy weight ≥110% of ideal body weight or body mass index over 30 kg/m2 or significant weight gain in early adulthood, between pregnancies, or in early pregnancyAge greater than 25 yearsPrevious delivery of a baby greater than 4.1 kgPersonal history of abnormal glucose toleranceMember of an ethnic group with higher than the background rate of type 2 diabetes (in most populations, the background rate is approximately 2 percent)Previous unexplained perinatal loss or birth of a malformed childMaternal birthweight greater than 4.1 kg or less than 6 pounds 2.7 kgGlycosuria at the first prenatal visitPolycystic ovary syndromeCurrent use of glucocorticoidsEssential hypertension or pregnancy-related hypertension
17 Maternal complications Worsening retinopathy – 10% new DR, 20% mild NPDR and 55% mod-severe NPDR progressesWorsening proteinuria. GFR decline depends on preconception creatinine and proteinuriaHypertension and Cardiovascular diseaseNeuropathy – No worsening (gastroparesis, nausea, orthostatic dizziness can be worsened)Infection
19 Neonatal complications Morbidity associated with preterm birthMacrosomia ± birth injury (shouldeer dystocia, brachial plexus injury)Polycythemia and hyperviscosityHyperbilirubinemiaCardiomyopathyHypoglycemia and other metabolic abnormalities (hypocalcemia, hypomagnesemia)Respiratory problemsCongenital anomalies
20 Congenital anomalies 2/3rd CVS or CNS,– 13-20 times common Cardiac( including great vessel anomalies) : most commonCentral nervous system (spina bifida/anencephaly) : 7.2%Skeletal: cleft lip/palate, caudal regression syndromeGenitourinary tract: ureteric duplicationGastrointestinal : anorectal atresia
21 Skeletal and central nervous system Caudal regression syndromeNeural tube defects excluding anencephalyAnencephaly with or without herniation of neural elementsMicrocephalyCardiacTransposition of the great vessels with or without ventricularVentricular septal defectsCoarctation of the aorta with or without ventricular septal defects or patent ductus arteriosusAtrial septal defectsCardiomegalyRenal anomaliesHydronephrosisRenal agenesisUreteral duplicationGastrointestinalDuodenal atresiaAnorectal atresiaSmall left colon syndrome
25 Whom to screen ? No consensus recommended screening ranges from selective screening of average- and high-risk individuals to universal diagnostic testing of the entire population dependent on the risk of diabetes in the population.Risk stratification based on certain variablesLow risk : no screeningAverage risk: at weeksHigh risk : as soon as possible
27 Low risk for GDM To satisfy all these criteria Age <25 years Not a member of an ethnic group with high prevalence of GDM (not Hispanic, Native American/Alaskan, Asian/Pacific Islander, African American)Normal prepregnancy body weight (not 20% or more over desired body weight or BMI 27 kg/m2 or more)No family history of diabetes in first-degree relatives.No history of abnormal glucose toleranceNo history of poor obstetric outcome
28 High risk Marked obesity Prior GDM (30-50% risk for recurrence) GlycosuriaStrong family history
29 When and how to screen? 24-28 weeks High risk First prenatal visit50 g glucose loading testHigh risk women – 3 hr GTT with 100 g glucose
31 50 g GTTA 50-g oral glucose load is given without regard to the time elapsed since the last meal and plasma or serum glucose is measured one hour laterA value ≥130 mg/dL is considered abnormal ; we use ≥130 mg/dL as the threshold for our patients.Capillary blood should not be used for screening unless the precision of the glucose meter is known, it has been correlated with simultaneously drawn venous plasma samples, and has met federal standards for laboratory testing.
32 100 g GTT Oral glucose tolerance test ( OGTT) with 100 gm glucose Overnight fast of at least 8 hoursAt least 3 days of unrestricted diet and unlimited physical activity> 2 values must be abnormalFasting> 95 mg/dl1-h> 180 mg/dl2-h> 155 mg/dl3-h> 140 mg/dl
33 75 g GTT ADA WHO Fasting > 95 mg/dl 1-h > 180 mg/dl 2-h OR2-h> 140 mg/dl
34 Whom and when to screen? Indian Scenario -The DIPSI Guidelines 75 gm GCT with single PG at 2 hrs –≥ 140 mg/dL is GDM≥ 120 mg/dL is DGGTUniversal screeningFirst trimester, if negative at 24 – 28 weeks and then at 32 – 34 weeks
36 MANAGEMENT ISSUES Patient education Medical Nutrition therapy Pharmacological therapyGlycemic monitoring: SMBG and targetsFetal monitoring: ultrasoundPlanning on delivery
37 Medical nutrition therapy GoalsAchieve normoglycemiaPrevent ketosisProvide adequate weight gainContribute to fetal well-beingNutritional planCalorie allotmentCalorie distributionCH2O intake
38 Calorie allotment30 kcal per kg current weight per day in pregnant women who are BMI 22 to 25.24 kcal per kg current weight per day in overweight pregnant women (BMI 26 to 29).12 to 15 kcal per kg current weight per day for morbidly obese pregnant women (BMI >30).40 kcal per kg current weight per day in pregnant women who are less than BMI 22.
39 Carb intakePostprandial blood glucose concentrations can be blunted if the diet is carbohydrate restricted. Complex carbohydrates, such as those in starches and vegetables, are more nutrient dense and raise postprandial blood glucose concentrations less than simple sugars.Carbohydrate intake is restricted to 33-40% of calories, with the remainder divided between protein (about 20%) and fat (about 40%).With this calorie distribution, 75 to 80 percent of women with GDM will achieve normoglycemia.
40 Calorie distribution Variable opinion Most programs suggest three meals and three snacks; however, in overweight and obese women the snacks are often eliminatedBreakfast — The breakfast meal should be small (approximately 10%of total calories) to help maintain postprandial euglycemia. Carbohydrate intake at breakfast is also limited since insulin resistance is greatest in the morning.Lunch — 30% of total caloriesDinner — 30% of total caloriesSnacks — Leftover calories (approximately 30% of total calories) are distributed, as needed, as snacks.
41 Monitoring BG Atleast 4 times Pre vs postprandial monitoring Fasting and 3 one hr postprandialPre vs postprandial monitoringBetter glycemic control (HbA1c value 6.5 versus 8.1 percent)A lower incidence of large-for-gestational age infants (12 versus 42 percent)A lower rate of cesarean delivery for cephalopelvic disproportion (12 versus 36 percent)
42 Monitoring BG Home monitoring Maintain log book Use a memory meter Calibrate the glucometer frequentlyHbA1CAncillary test for feedback to the patientLower values when compared to nonpregnant state – lower BG and increase in red cell mass and slight decrease in life span – measured every 2-4 weeksTarget < 5.1%
43 Studies report no to moderate correlations between HbA1 and different components of the glucose profile when an HbA1 result of 4% to 5% includes a capillary blood glucose range of 50 to 160 mg/dL.Levels of HbA1c are related to the rate of congenital anomalies and spontaneous early abortions in pre-existing diabetes, but the use of this measure, which retrospectively reflects glycemic profile in the last 10 weeks, for treatment evaluation in GDM is questionable. In addition, the association between glycosylated hemoglobin and pregnancy outcome in GDM or prediction of macrosomia is poorGlycosylated protein and fructosamine widely variable and not yet established
44 Glycemic targets (ACOG) Fasting venous plasma ≤ 95 mg/dl1 hour postprandial ≤ 140 mg/dl2 hour postprandial ≤ 120 mg/dlPre-meal ≤ 100 mg/dlA1C ≤ 6%ADApremeal2 hr postmeal not more than 155These are venous plasma targets, not glucometer targets
45 PHARMACOLOGICAL INTERVENTION If the FPG at diagnosis is ≥ 120, can consider immediate therapy.Otherwise, MNT for 2 weeksIf majority FPG (4/7) > 95 or PP > 120 then to start on insulin.
46 Insulin ≈ 15% need insulin Total dose varies. ≈ 0.7 to 2 units per kilogram (present pregnant weight)FBG high – Night NPH ≈ 0.2 units/kgPPBG high – bolus ≈ 1.5 units/10 gm CH2O for breakfast and ≈ 1 unit /10 gm CH2O for lunch and dinnerIf both pre and postprandial BG high or if the woman's postprandial glucose levels can only be blunted if starvation ketosis occurs - four injection/day regimen.Total 0.7 unit/kg up to week 180.8 unit/kg for weeks 18 to 260.9 unit/kg for weeks 26 to 361. unit/kg for weeks 36 to term.In a morbidly obese woman, the initial doses of insulin may need to be increased to 1.5 to 2. units/kg to overcome the combined insulin resistance of pregnancy and obesity.
47 OHA in pregnancy Systematic review by John Hopkins University maternal glucose levels did not differ substantially between gravidae treated with insulin versus those treated with oral glucose-lowering agentsthere was no consistent evidence of an increase in any adverse maternal or neonatal outcome with use of glyburide, acarbose, or metformin compared with use of insulinInconsistent data. ADA, ACOG, USFDA do not endorse.
48 OHA in pregnancy Tolbutamide and chlorpropamide Glibenclamide Cross placenta. Fetal hperinsulinemia. Prolonged fetal hypoglycemiaGlibenclamideMinimal transplacental transportObservational studies – no excess anomalies or hypoglycemiaOnly RCT – 404 women. Glib vs insulin. No difference
49 second-generation sulfonylureas especially glyburide, do not significantly cross the diabetic or nondiabetic placenta. Fetal concentrations reached no more than 1% to 2% of maternal concentrations.tolbutamide diffused across the placenta most freely, followed by chlorpropamide, then glipizide, with glyburide crossing the least.Metformin crosses placenta – not teratogenic in rat models
50 OHA in pregnancy Metformin Acarbose Thiazolidinediones and GLP-1 Category BNo adverse outcome after first trimesterSecond, third trimester safe and effectiveVs. insulin – no serious adverse effectsNo studies vs. glibenclamideAcarboseTwo prelim studiesThiazolidinediones and GLP-1Not studied
52 Fetal monitoring Baseline ultrasound : fetal size At weeks: major malformationsfetal echocardiogram26 weeks onwards: growth and liquor volumeIII trimester: frequent USG for accelerated growth( abdominal: head circumference)
53 Timing of delivery Small risk of late IUD even with good control Delivery at 38 weeks – to avoid late still birth and fetal growth leading to shoulder dystociaVaginal delivery: preferredCaesarian section only for routine obstetric indicationjust GDM is not an indication !Unfavorable condition of the cervix is a problem4500 grams, cesarean delivery may reduce the likelihood of brachial plexus injury in the infant (ACOG). Assessing fetal weight accurately is a problem
54 Management of labor and delivery Maternal hyperglycemia in labor: fetal hyperinsulinemia,worsen fetal acidosis and neonatal hypoglycemiaInsulin requirements come downMaintain sugars: mg/dlRoutine GDM dietMaintain basal glucose requirementsMonitor sugars 1-4 hrly intervals during labourGive insulin as infusion only if sugars more than 120 mg/dl
55 Glycemic management during labour Later stages of labour: start dextrose to maintain basal nutritional requirements: ml/hr of 5% dextroseElective LSCS: check FBS, if in target no insulin, start dextrose dripContinue hourly SMBGPost delivery keep patients on dextrose-normal saline till fedNo insulin unless sugars more than normal nonpregnant levels
56 Post partum follow up Check BG before discharge Breast feeding: helps in weight loss. Insulin, tolbutamide compatible. Chlropropamide secreted small amounts – watch for hypoglycemia in infant. Glyburide and glipizide not secreted Metformin secreted - no adverse effectsLifestyle modification: exercise, weight reductionOGTT at 6-12 weeks postpartum: classify patients into normal/impaired glucose tolerance and diabetesContraception – low dose EP can be used. Progestin only pills shown to increase risk of T2DM in GDMPreconception counseling for next pregnancy
57 Immediate management of neonate Hypoglycemia : 50 % of macrosomic infants5–15 % optimally controlled GDMStarts when the cord is clampedExaggerated insulin release secondary to pancreatic ß-cell hyperplasiaIncreased risk : blood glucose during labor and delivery exceeds 90 mg/dlAnticipate and treat hypoglycemia in the infant
58 Management of neonate Hypoglycemia <40 mg/dl Encourage early breast feedingIf symptomatic give a bolus of 2- 4 ml/kg, IV 10% dextroseCheck after 30 minutes, start feedsIV dextrose : 6-8 mg/kg/min infusionCheck for calcium, if seizure/irritability/RDSExamine infant for other congenital abnormalities
60 Future risks - MotherAtleast 6 weeks post delivery, 75 g OGTT for all GDM≥ 90% normoglycemicRecurrence of GDM – 30-60%OlderMultiparaWeight gain interpregnancyHigher infant BW in index pregnancyIGT and T2DM20% IGT postpartum6m , 15m and 9 y
61 Who will progress to DM? WC and BMI – stronset predictors AutoantibodiesDM at earlier gestational ageGestational requirement of insulinHigher FBGHigher BG on OGTTNeonatal hypoglycemiaRecurrent GDM
62 Preconception counselling Diabetic mother : glycemic control with insulin/SMBGTarget: HbA1c < 7%Folic acid supplementation: 5 mg/dayEnsure no transmissible diseases: HBsAg, HIV, rubellaTry and achieve normal body weight: diet/exerciseStop drugs : oral hypoglycemic drugs, ACE inhibitors, beta blockers
63 Risk of developing DM in offspring Type 1 -Father - 1 in 17 riskMother - 1 in 25 risk if, at the time of pregnancy, the mother is < 25 years of age but a 1 in 100 risk if the mother is 25 years of age or older.These risks are doubled if the affected parent developed diabetes before age 11.Both parents have type 1 diabetes - 1 in in 4.Type 2 polyglandular autoimmune syndrome – 50%Type 2Single parent - 1 in 7 if the parent was diagnosed before age 50 and 1 in 13 if the parent was diagnosed after age 50.There is some evidence that the offspring's risk is greater when the parent with type 2 diabetes is the mother. IBoth parents - 1 in 2.
64 Conclusion Gestational diabetes is a common problem in India Risk stratification and screening is essential in all Indian pregnant womenTight glycemic targets are required for optimal maternal and fetal outcomePatient education is essential to meet these targetsLong term follow up of the mother and baby is essential