Gestational diabetes mellitus

a summary of diabetes in pregnancy

1. DIABETES IN PREGNANCY

2. Pre-existing DM Gestational diabetes

3. Gestational diabetes (GDM) is defined as any degree of impaired glucose tolerance of with onset or first recognition during pregnancy . Many are denovo pregnancy induced Some are type 2 ( 35-40%) 10% have antibodies

4. Difficult to distinguish pregestational Type 2 DM and denovo GDM Fasting hyperglycemia blood glucose greater than 200 mg/ dL on OGT acanthosis nicgrans HbA1C > 6% a systolic BP > 110 mm Hg BMI > 30 kg/m2 Fetal anomalies Clues for Type 1 Lean DKA during pregnancy Severe hyperglycemia requiring large doses of insulin

5. Fuel metabolism in pregnancy Goal is uninterrupted nutrient supply to fetus The metabolic goals of pregnancy are 1) in early pregnancy to develop anabolic stores to meet metabolic demands in late pregnancy 2) in late pregnancy to provide fuels for fetal growth and energy needs.

6. Glucose metabolism in pregnancy Early pregnancy E2/PRL stimulates b cells –Insulin sensitivity same and peripheral glucose utilisation – 10% fall in BG levels Late pregnancy Fetoplacental unit extracts glucose and aminoacids , fat is used mainly for fuel metabolism Insulin sensitivity decreases progressively upto 50-80% during the third trimester variety of hormones secreted by the placenta, especially hPL and placental growth hormone variant, cortisol, PRL,E2 and Prog

7. Glucose metabolism in pregnancy Fetus Fat Glucose Aminoacids Insulin Hyperinsulinemia FASTING accelerated starvation and exaggerated ketosis (maternal hypoglycemia, hypoinsulinemia , hyperlipidemia, and hyperketonemia ) FED hyperglycemia, hyperinsulinemia , hyperlipidemia, and reduced tissue sensitivity to insulin

8. RISK FACTORS History of macrosomia:birth weght >4 Kg,h /o GDM previous pregnancy Race Polycystic ovarian syndrome Essential hypertension or pregnancy-related hypertension history of spontaneous abortions and unexplained stillbirths strong family history of diabetes (especially in first-degree relatives) obesity ( [BMI] > 30) age older than 25 years persistent glucosuria

9. “NO KNOWN RISK FACTORS IN 50% OF GDM” ADA recommends selective screening for GDM, but according to indian guidelines we follow universal screening

10. Maternal complications Worsening retinopathy – 10% new DR, 20% mild NPDR and 55% mod-severe NPDR progresses Worsening proteinuria. GFR decline depends on preconception creatinine and proteinuria Hypertension and Cardiovascular disease Neuropathy – No worsening ( gastroparesis , nausea, orthostatic dizziness can be worsened) Infection

11. Fetal: Congenital abnormalities Increased neonatal and perinatal mortality Macrosomia Late stillbirth Neonatal hypoglycemia Polycythemia jaundice

12. SCREENING AND DIAGNOSIS

13. Diagnosis of GDM The WHO 1999 criteria. Introduced in 1999. Glucose load is 75g. GDM diagnosed if the plasma glucose is 140mg /dl or above 2 hours after the glucose load. In 2013 ,WHO dropped in own 1999 criteria and accepted the IADPSG criteria.

14. IADPSG guidelines Screening for GDM. Performed at 24 to 28 weeks of gestation. 75g two hour OGTT is used. GDM is diagnosed if any one value exceeds the thresholds shown below. fasting 1hr 2hr Plasma glucose ≥92 ≥180 ≥153 (mg/dl)

15. 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 DGGT >200mg/dl is diabetes Universal screening First trimester, if negative at 24 – 28 weeks and then at 32 – 34 weeks

16. Why in India,separate guidelines for screening? Indian females-11 fold increased risk of GDM than Caucasians. Prevalence is 16.55% Universal screening detects more number of GDM. Single blood glucose measurement after GCT,economically feasible,more patient compliance.

17. MANAGEMENT

18. MANAGEMENT ISSUES Patient education Medical Nutrition therapy Pharmacological therapy Glycemic monitoring: SMBG and targets Fetal monitoring: ultrasound Planning on delivery

19. If FPG >120,start insulin Others:Advise MNT,3 days of SMBG,fasting,and 3 one and half hour post prandial blood glucose. After MNT,1-2 weeks,start insulin if majority of fasting ie,four -seven >90 Or majority of any one of PP >120

20. Medical nutrition therapy Goals Achieve normoglycemia Prevent ketosis Provide adequate weight gain Contribute to fetal well-being Nutritional plan Calorie allotment Calorie distribution CH2O intake

21. Calorie allotment 30 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.

22. Postprandial 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 .

23. Calorie distribution Variable opinion Most programs suggest three meals and three snacks; however, in overweight and obese women the snacks are often eliminated Breakfast — 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 calories Dinner — 30% of total calories Snacks — Leftover calories (approximately 30% of total calories) are distributed, as needed, as snacks.

24. Diabetes in Pregnancy: Physical Activity Unless contraindicated, physical activity should be included in a pregnant woman’s daily regimen Regular moderate-intensity physical activity (eg, walking) can help to reduce glucose levels in patients with GDM Other appropriate forms of exercise during pregnancy Cardiovascular training with weight-bearing, limited to the upper body to avoid mechanical stress on the abdominal region

25. Monitoring BG Atleast 4 times-self monitoring Fasting and 3 one and half hour postprandial After achieving target level,lab monitoring till 28 weeks once in a month 28-32 weeks once in 2 weeks >32 once a week Other parameters to be monitored:fundus,micro albuminuria

26. Glycemic targets Mean plasma glucose of 105 mg/dl Achieved by maintaining FPG at 90 & PP at 120 Mean plasma glucose should never go below 86

27. INSULIN THERAPY Type of insulin used-always human insulin or analogues In India,basal insulin is usually given as NPH. Basal may be provided with long acting or intermediate acting or continuos infusion Insulin for post prandial control-short acting(regular or analogue) NPH-intermediate acting-category B Detemir -long acting category B Lispro,aspar ultra short acting-category B Glargine -long acting-category C

28. INSULIN THERAPY NPH is usually started at 4 units and then titrated If morning PP is more,regular insulin in morning If predinner is high,night dose of rapid insulin Mixed split regimen-total insulin requirement-2/3 in morning,1/3 night,of each dose 1/3 rapid and 2/3 intermediate acting.

29. Insulin ≈ 15% need insulin Total dose varies. ≈ 0.7 to 2 units per kilogram (present pregnant weight) FBG high – Night NPH ≈ 0.2 units/kg PPBG high – bolus ≈ 1.5 units/10 gm CH2O for breakfast and ≈ 1 unit /10 gm CH2O for lunch and dinner If 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 18 0.8 unit/kg for weeks 18 to 26 0.9 unit/kg for weeks 26 to 36 1. 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.

30. Status of OHA in pregnancy Metformin and the sulfonylurea glyburide are the 2 most commonly prescribed oral antihyperglycemic agents during pregnancy Due to efficacy and safety concerns, the ADA and DIPSI does not recommend oral antihyperglycemic agents for gestational diabetes mellitus (GDM) or preexisting T2DM Medication Crosses Placenta Classification Notes Metformin Yes Category B Metformin and glyburide may be insufficient to maintain normoglycemia at all times, particularly during postprandial period Glyburide Minimal transfer Some formulations category B, others category C

31. Fetal monitoring USG:18-20 weeks,anomaly scan Fetal ECHO:20-24 weeks From 26 weeks,every 2-3 weeks-liquor volume Abdominal circumference monitoring>70 indication of insulin Chromosomal abnormalities,NTD

32. Management Intrapartum Attention to labor pattern, as cephalopelvic disproportion may indicate fetal macrosomia If steroids or beta agonists used,increase insulin Skip morning insulin on day of induction. Usually no need of insulin while labour . Hourly blood glucose monitoring during active labor, with insulin drip if necessary Notify pediatrics if patient has poorly controlled blood sugars antepartum or intrapartum

33. 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

34. Metformin and glyburide are secreted into breast milk and are therefore contraindicated during lactation Breastfeeding plus insulin therapy may lead to severe hypoglycemia 1 Greatest risk is in women with T1DM Preventive measures are: reduce basal insulin dosage and/or carbohydrate intake prior to breastfeeding For baby,start early breast feeding,CBG at 1 hour and 4 values in first 24 hours,before each feed.<44 is considered hypoglycemia.

35. 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

36. Who will progress to DM? WC and BMI – stronset predictors Autoantibodies DM at earlier gestational age Gestational requirement of insulin Higher FBG Higher BG on OGTT Neonatal hypoglycemia Recurrent GDM

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