GESTATIONAL DIABETES MELLITUS Dr Abha Gupta Professor of Medicine, LLRM Medical College, Meerut  

Definition

Carbohydrate intolerance of any degree with onset or first recognition during pregnancy. ADA (2014 guidelines) defined GDM as “diabetes diagnosed during pregnancy that is not clearly overt diabetes”.

Epidemiology

The overall worldwide prevalence :1% - 20%. International Diabetes federation (2013) : worldwide 16% live births complicated by hyperglycemia during pregnancy. In a study from Haryana the prevalence was GDM was found to be 7.1% while in another study from South India it was 16.55%

WHO Criteria 1999

GDM to be diagnosed if any of the following criteria is met: FPG ≥ 126 mg/dl (7 mmol/L) 2hr post 75 gm OGTT ≥ 140 mg/dl ( 7.8 mmol/L)

NEED TO CHANGE DIAGNOSTIC CRITERIA

Was not evidence based, over 10 years old hence needed to be updated in light of new data Does not differentiate between overt diabetes and glucose intolerance in pregnancy. The diagnostic level of FPG ≥ 126mg/dl( 7 mmol/lt) – universally considered to be too high.

Diabetes during pregnancy, symptomatic or not , is associated with adverse pregnancy outcomes- what level of hyperglycemia should be treated is not clear. Difference in the management approach in overt diabetes and impaired glucose tolerance during pregnancy.

WHO -2013 criteria Gdm : Any of the following Diabetes in pregnancy : Any of the following Parameters Level fasting plasma glucose ≥5.1-6.9 mmol/l (92 -125 mg/dl) 1-hour plasma glucose following a 75g oral glucose load ≥ 10.0 mmol/l (180 mg/dl) 2-hour plasma glucose following a 75g oral glucose load ≥ 8.5-11.0 mmol/l (153 -199 mg/dl) Parameters Level fasting plasma glucose ≥ 7.0 mmol/l (126 mg/ dl) 2-hour plasma glucose following a 75g oral glucose load ≥ 11.1 mmol/l (200 mg/dl) random plasma glucose in the presence of diabetes symptoms ≥ 11.1 mmol/l (200 mg/ dl) Diagnostic criteria for GDM is based on adverse pregnancy outcomes as derived from HAPO, 2008 (Hyperglycemia and adverse pregnancy outcomes)study and the recommendations of IADPSG (International assoc. Of Diabetes & pregnancy study group) consensus panel.

ADA’s “One-Step” Strategy for GDM 75-g OGTT, after overnight fast (≥8 h), with PG measurement fasting and at 1 h and 2 h, at 24-28 wks in women not previously diagnosed with overt diabetes    GDM diagnosis made if PG values meet or exceed:  Fasting: 92 mg/dl (5.1 mmol/L) 1 h: 180 mg/dl (10.0 mmol/L) 2 h: 153 mg/dl (8.5 mmol/L) 

ADA’s “Two-Step” Strategy for GDM   50-g GLT (nonfasting) with PG measurement at 1 h (Step 1), at 24-28 wks in women not previously diagnosed with overt diabetes If PG at 1 h after load is ≥140 mg/dl  (7.8 mmol/L), proceed to 100-g OGTT  (Step 2), performed while patient is fasting GDM diagnosis made when two or more PG levels meet or exceed: Fasting: 95 mg/dl or 105 mg/dl (5.3/5.8) 1 hr: 180 mg/dl or 190 mg/dl (10.0/10.6) 2 hr: 155 mg/dl or 165 mg/dl (8.6/9.2) 3 hr: 140 mg/dl or 145 mg/dl (7.8/8.0)

Pathophysiology of GDM

Progressive insulin resistance No adequate insulin GDM Placental hormones Maternal adiposity  diabetogenic adipokines Defect in β-cell insulin secretion - Defective first phase insulin response - Lower insulin response to given glycemic stimulus

Whom & when to screen??

High risk patients Higher pre-pregnant BMI > 27 kg/m2 Increased gestational weight gain Ethnicity  South Asian, Middle East, Black Caribbean Maternal age over 25 years Previous GDM Previous macrosomic baby weighing 4.5 kg or above, Multiparity Twin pregnancy Family history of diabetes(first-degree relative with diabetes)

When to screen Women with previous GDM As soon as possible after booking Repeat at 24-28 weeks if first test normal All other high risk women - 24-28 weeks Screening  75 gm 2 hr OGTT - NICE 2015

Maternal & Fetal complications

Maternal complications Miscarriage Pre-eclampsia/ hypertensive disorders of pregnancy Increased obstetric interventions Long term maternal increased risk of T2DM (50% in next 20 years),CVD,Metabolic syn

Fetal complications Unexplained stillbirth Macrosomia/LGA baby Shoulder dystocia Neonatal hypoglycemia/hypocalcemia/ hyperbilirubinemia Delayed lung maturity Long term-Childhood obesity(2 fold), T2DM (6 fold)and metabolic syndrome(4 fold)

Why to treat?? GDM has been demonstrated to be an independent risk factor for various adverse pregnancy outcomes. HAPO study(Hyperglycemia and adverse pregnancy outcomes-2008)- international multicentric cohort of 25,505 pregnant women GDM treatment consistently demonstrates significant decreases in adverse outcomes such as macrosomia, LGA , shoulder dystocia, preeclampsia and and obstetric interventions. - .ACHOIS Study -2005 -Systematic review by Flavinga et al- effectiveness of GDM treatment. Diabetic research and clinical practice , 2012

Management of GDM

Glycemic Targets in Pregnancy- ADA (2015) GDM targets   Targets for preexisting type 1 or 2 DM  Premeal, bedtime, overnight glucose:  60-99 mg/dL (3.3-5.4 mmol/L) Peak postprandial glucose: 100-129 mg/dL (5.4-7.1 mmol/L) A1C: <6.0% Preprandial: ≤95* mg/dL (5.3 mmol/L) and either  1-hr postmeal: ≤140 mg/dL (7.8 mmol/L) 2-hr postmeal: ≤120 mg/dL (6.7 mmol/) * Diabetes in Pregnancy Study Group India  90mg% For GDM pts on pharmacotherapy maintain plasma glucose levels : >4mmol/lt (72 mg/dl) – NICE 2015

Management components Medical Nutrition Therapy Physical exercise  30 min walk (NICE 2015) Pharmacotherapy SMBG Counseling regarding hypoglycemic symptoms

Medical Nutrition Therapy

Carbohydrate controlled meal plan that promotes adequate nutrition and appropriate weight gain, normoglycemia and absence of ketosis. Food plan must be flexible and should incorporate modifiable components

Calories IBW – 30 kcal/kg/d Overweight (1.2 – 1.5 X IBW) – 24kcal/kg/d Obese > 1.5 X IBW – 12-15 kcal/kg/d Underweight < 0.8 X IBW – 40 kcal/kg/d Components Carbohydrate 40% Protein 20% Fat 40 % (saturated < 7%)

Since there is defect in first phase of insulin secretion the challenge of quantity of food at one time should be less. 3 major meals and 3 snacks per day - Total calories to be divided into 9 portions - 2 portions = major meal 1 portions = snack

Decreased carbohydrate load in the breakfast Morning cortisol surge (Dawn phenomenon) release of blood glucose from stored sources and hepatic gluconeogenesis high blood glucose levels. Split the breakfast portion into two equal halves  prevents undue peak in blood glucose levels. Bedtime snack prevents accelerated starvation and ketosis overnight.

Pharmacotherapy

Pharmacological management ADA, ACOG, NICE, Diabetes in Pregnancy Study Group in India recommends insulin for maternal hyperglycemia not meeting the target levels even with diet and exercise after about 2 weeks. Most insulins are category B; glargine and glulisine are category C.

Status of OHA

Metformin is commonly used because of strong evidence of its effectiveness in pregnancy and lactation with minimal risk of teratogenisity (pregnancy cat B, USFDA approved-1995, yet not by UK marketing authorization)

Oral hypoglycemics like glibenclamide can be considered (during second and third trimester) in patients in whom blood glucose targets are not met with metformin but who decline insulin therapy or who cannot tolerate metformin. Acarbose-found safe in pergnancy.(Bertini et al,perinatal outcomes &use of OHA.J Perinat med.2005)

Antenatal management - Oral hypoglycemics (contd.) Noninsulin medications lack sufficient long-term safety data Because of limited safety data global recommendations still have kept insulin as the drug of choice.

Labor and delivery

Target glucose of 80 to 110 mg/dL Maternal glucose > 110 mg/dL insulin drip If the woman does not require insulin during the prenatal period, labor and delivery can likely proceed without special attention to maternal glycemia. If insulin is required, and labor and delivery are to be scheduled, it is preferable to schedule for the morning hours. In this case, the usual insulin dose can be administered the evening before the scheduled delivery, and the morning dose can be held.

If the mother took insulin and spontaneous labor ensues, a dextrose infusion with the rate adjusted to a target glucose of 80 to 110 mg/dL may be required to prevent maternal hypoglycemia. The infant is at greatest risk of hypoglycemia in the first hours after birth therefore mother should feed their babies as soon as possible after birth and then at frequent intervals

Post-partum – ABCDEFG of post- partum care A- assessment of hyperglycemic status B- breastfeeding C- contraception(avoid progesterone-only therapy) D- diet E- exercise F- family oriented motivation & education G- goals

All patients with GDM should continue lifestyle management including diet , regular physical exercise and maintenance of ideal body weight

Post-partum screening Women with GDM to be reclassified at 6 weeks with 75gm OGTT (ADA) If BS profile – WNL  reassess every 3 years If results  prediabetic rangeassess annually If results  diabetic range manage as a case of diabetes

Goals of postpartum care Maintaining euglycemic status Monitoring cardiometabolic parameters - BP Lipid profile Weight control

Key notes… Since the HAPO and other studies have shown that the association of risk of adverse pregnancy outcomes is continuous with increasing glucose level, WHO new (2013) diagnostic criteria for GDM is based on prognostic accuracy meaning risk of adverse pregnancy outcomes rather than on diagnostic accuracy. Maternal metabolic characteristics are crucial determinants of insulin resistance during pregnancy and in offsprings.

Treatment of GDM is effective in reducing many adverse outcomes , the risk reduction for these outcomes is in general large, the no. to treat is low and the quality of evidence is adequate, which justifies treatment of GDM. Treatment of choice is diet , physical exercise with/without insulin.

Interventions esp. healthy diet, exercise & weight reduction before ,during and after pregnancy might be a key to prevent the vicious cycle that contributes to the epidemic of obesity, insulin resistance and Type 2 DM .