diabetes in pregnancy-a social stigma an overview

diabetes in pregnancy-a social stigma an overview

1. Diabetes in Pregnancy

2. Diabetes mellitus State of carbohydrate intolerance resulting from inadequacy of insulin secretion or ineffectiveness of insulin action. It can broadly be divided into:- Pre-gestational DM Type 1 DM Type 2 DM Other types Gestational DM

3. Diabetes the burden Prevalence has increased worldwide. Epidemic proportion in South Asia India has highest no of Diabetics (WHO)  31.7million (2000) 2-4%-rural population 7-10%-urban population  79.4million (projected in 2030)

4. Diabetes classification (Etiological classification) Type 1 Type 2 Gestational Diabetes Other types Genetic mutations of β-cell function—MODY Genetic defects in insulin action Genetic syndromes—Down, Klinefelter, Turner Diseases of the exocrine pancreas—pancreatitis, cystic fibrosis Endocrinopathies—Cushing syndrome, pheochromocytoma Drug or chemical induced—glucocorticosteroids, thiazides, β-adrenergic agonists Infections—congenital rubella, cytomegalovirus, coxsackievirus

5. Diabetes classification (White’s classification) Proposed by Priscilla White in 1932 Not used nowadays Mainly emphasizes on age, duration and presence of vasculopathy. Was modified by ACOG in 1986

6. Diabetes classification (White’s classification)

7. Diabetes classification (ADA’s classification recommended by ACOG) Gestational Diabetes Diagnosed during pregnancy that is not clearly overt(type 1 or Type 2) Type 1 Diabetes Resulting from β-cell destruction, usually leading to absolute insulin deficiency Without vascular complications With vascular complications (specify which) Type 2 Diabetes Due to inadequate insulin secretion in the face of increased insulin resistanse Without vascular complications With vascular complications (specify which) Other types of diabetes Genetic in origin, associated with pancreatic disease, drug induced or chemically induced. Data from American Diabetes Association, 2012

8. Effect of pregnancy on maternal glucose metabolism  In early pregnancy,  basal glucose insulin levels glucose tolerance As pregnancy advances, basal insulin post parandial insulin Maternal & placental hormones human chorionic somatomammotropin Estrogen Progesterone Prolactin Cortisol unchanged normal or slightly improved increases increases As a result, during pregnancy, the normal fasting blood glucose is 65±9mg /dl. The mean non-fasting blood glucose is 80±10 mg/dl. And the Postprandial elevations never exceeds 140 mg/dl.

9. Effect of pregnancy on fetal glucose metabolism Oxygen Free FA Gluc o se Amino ặ Endothelial function Tone regulation Angiogenesis Fetoplacental blood flow Fetal growth From mother Inside fetus Fetal plasma glucose level is always 10gm/dl lower than mothers

10. Diabetes in Pregnancy Pregestational diabetes Gestational diabetes Pregnancy in pre-existing diabetes Type 1 diabetes Type 2 diabetes Diabetes diagnosed in pregnancy

11. Diabetes in pregnancy Importance of classifying DM as pre-gestational or gestational In June 2008, IADPSG experts agreed that it was important to identify women diagnosed with Diabetes during early pregnancy and level them as Overt Diabetes and not GDM(as was done earlier) as the needs and implications for the mother and her fetus were different for this group, which are as follows: Increased risk of congenital malformations in the offspring. Risk of diabetic complications as Nephropathy and Retinopathy. Need for prompt treatment and normalization of blood glucose levels. Need to ensure proper treatment of diabetes after pregnancy.

12. Gestational diabetes de f ined as  Gestational diabetes is car b o h ydr a te intol e ra n ce o f v aria b le seve r ity with onset o r first recognition during pregnancy (ACOG, 2013). includes  This so m e de f inition und o ubtedly women with previously unrecognized overt diabetes.

13. Effect of Diabetes on Pregnancy With pre-gestational or overt diabetes, the embryo, fetus, and mother frequently experience serious complications directly attributable to diabetes. The likelihood of successful outcomes with overt diabetes is related somewhat to the degree of glycaemic control, but more importantly, to the degree of underlying cardiovascular or renal disease.

14. Fetal effects of Overt Diabetes Spontaneous Abortion. Several studies have shown that poor glycaemic control (A1c > 7 %), was associated with a threefold increase in the spontaneous abortion rate (Galindo, 2006) . Preterm Delivery. Overt diabetes is an undisputed risk factor for preterm birth. It is associated with fivefold increase in preterm delivery (Canadian Study)

15. Fetal effects of Overt Diabetes Malformations. The incidence of major malformations in women with type 1 diabetes is doubled (Eidem, 2010; Sheffield, 2002). These account for almost half of perinatal deaths in diabetic pregnancies. At least three interrelated molecular chain reactions have been linked to the mechanism behind poor glycaemic control and increased risk for major malformations (Reece, 2012). alterations in cellular lipid metabolism excess production of toxic superoxide radicals activation of programmed cell death. Risk of an isolated cardiac defect was fourfold higher compared with the twofold increased risk of noncardiac defects (Correa, 2008). The caudal regression sequence is a rare malformation frequently associated with maternal diabetes (Garne, 2012) .

16. Fetal effects of Overt Diabetes Altered Fetal Growth. Growth may be diminished due to malformations and substrate deprivations due to placental insufficiency Fetal overgrowth(macrosomia) is a more common and is due to maternal hyperglycaemia and fetal hyperinsulinemia. Raised HC/AC ratios, Increased risk of shoulder dystocia or caesarean delivery.

17. Fetal effects of Overt Diabetes Unexplained Fetal Demise. 3-4x higher risk of fetal death, typically without an identifiable cause. 7x higher in women with hypertension with overt diabetes. The infants are typically LGA and die before labour usually after 35weeks of gestation. Due to poor glycaemic control and fetal lactic acidosis. Hydraminos. Diabetic pregnancies are often complicated by excess amniotic fluid. A likely albeit unproven explanation is that fetal hyperglycemia causes polyuria.

18. Neonatal effects of Overt Diabetes Hypoglycemia Rapid drop of blood glucose post delivery Due to fetal beta cell hyperplasia induced by chronic maternal hyperglycemia. Strict maternal glyceamic control reduces the risk of fetal hypoglycemia. Polycythemia and hyperbilirubinemia Increased EPO levels due to fetal hypoxia and IGF May lead to renal vein thrombosis. Polycythemia leads to increased bilirubun load.

19. Neonatal effects of Overt Diabetes Hypertrophic Cardiomyopathy Mostly affects the interventricular septum and ventricular wall. In most of the affected, it resolves after delivery. Hypocalcemia one of the potential metabolic derangements in neonates of diabetic mothers. cause has not been explained. Theories include aberrations in magnesium– calcium economy, asphyxia, and preterm birth. Cognitive impairment Inheritance of diabetes

20. Maternal effects of Overt Diabetes Diabetic nephropathy Diabetes is a leading cause of ESRD Clinically detectable nephropathy begins with microalbuminuria—30 to 300 mg/24 hours. This may manifest as early as 5 years after diabetes onset. Macroalbuminuria—more than 300 mg/24 hours— develops in patients destined to have end-stage renal disease. If Sr.Creat > 1.5mg/dl may accelerate progression to ESRD. Hypertension almost invariably develops during this period, and renal failure ensues typically in the next 5 to 10 years.

21. Maternal effects of Overt Diabetes Diabetic retinopathy The presence and severity is related to the degree of the glycaemic control. A variety of lesions may be found which include Micro aneurysms, dot-blot hemorrhages, hard exudates, cotton wool infarcts; and proliferative retinopathy with marked neovascularization. Proliferative retinopathy should be ideally treated by laser photocoagulation before conception as it may lead to retinal or vitreous hemorrhage during delivery.

22. Maternal effects of Overt Diabetes Diabetic neuropathy Both autonomic and peripheral neuropathies are rare in pregnancy. It is however possible that patient with gastroparesis may suffer exaggerated nausea and vomiting. Proper foot care instruction should be given to all diabetic women. Preeclampsia Hypertension that is induced or exacerbated by pregnancy is the complication that most often forces preterm delivery in diabetic women. The incidence of chronic and gestational hypertension and especially preeclampsia is remarkably increased in diabetic mothers.

23. Maternal effects of Overt Diabetes Diabetic ketoacidosis This serious complication develops in approximately 1 percent of diabetic pregnancies (Hawthorne, 2011). It is most often encountered in women with type 1diabetes. It is increasingly being reported in women with type 2 or even those with gestational diabetes (Sibai, 2014). Diabetic ketoacidosis (DKA) may develop with hyperemesis gravidarum, β-mimetic drugs given for tocolysis, infection, and corticosteroids given to induce fetal lung maturation. An important cornerstone of management is vigorous rehydration with crystalloid solutions of normal saline or Ringer lactate.

24. Fetal effects of GDM Adverse consequences of gestational diabetes differ from those of pregestational diabetes. Unlike in women with overt diabetes, rates of fetal anomalies do not appear to be substantially increased (Sheffield, 2002). Fetal Macrosomia Maternal hyperglycemia prompts fetal hyperinsulinemia, particularly during the second half of pregnancy. This in turn stimulates excessive somatic growth. Neonatal Hypoglycemia Neonatal hyperinsulinemia may provoke hypoglycemia within minutes of birth.

25. Maternal effects of GDM Maternal Obesity In women with gestational diabetes, maternal BMI is an independent and more substantial risk factor for fetal macrosomia than is glucose intolerance (Ehrenberg, 2004; Mission, 2013). increased maternal abdominal subcutaneous fat thickness as measured by sonography at 18 to 22 weeks gestation correlated with BMI and was a better predictor of gestational diabetes (Suresh and colleagues,2012)

26. Diagnosis of Pregestational Diabetes Diagnosis of pre-gestational diabetes is made if patient presents with the signs and symptoms of diabetes along with the BPG levels above the normal during her 1 st antenatal visit. Other than that the criteria for diagnosis for those women who for the first time are tested is shown in the slide:-

27. Diagnosis of Pregestational Diabetes

28. Diagnosis of GDM Diagnosis of GDM is mainly done as Screening by OGT based on risk assessment during antenatal check up. The two recommended methods of screening for GDM are:- One Step approach (IADPSG & ADA recommended) Using 75gm of glucose Two step approach (ACOG & NDD group recommended) Using 50gm glucose followed by 100gm.

29. Oral Glucose Tolerance Test  One Step OGT  Two step OGTT 75 gm of glucose at 24-28 wks Fasting ≥ 92 mg/dl 1h PP ≥ 180 mg/dl 2h pp ≥ 153 mg/dl 50 gm of glucose at 24-28 wks 1h PP ≥ 140 mg/dl 100 gm of glucose at 24-28 wks

30. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management Contraception

31. Diabetes in Pregnancy: management 2 groups of patients Pregnant women with established diabetes (Pregestational DM) Pregnant women with new onset diabetes (GDM)

32. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management Contraception

33. Management of Pregestational Diabetes Preconceptional counselling Attain a preconception A1C of ≤7.0% Assess for and manage any complications. Fundoscopy (to rule out retinopathy) Assesment of renal function (to rule out nephropathy) Serum creatnine Spot urinary microalbumin:creatnine ratio Protein:creatnine ratio Cardiac evaluation by ECG, TMT if >35yrs old Co-existing hypertension/dyslypidemia/CAD/family history/smoking/renal disease. Blood pressure <130/80 mm Hg Protein excretion levels <150 mg/24 hours Free T 4 >1.0 but <1.6 ng/dL TSH <2.5  IU/mL

34. Management of Pregestational Diabetes Women with type 2 diabetes who are planning a pregnancy should switch from non-insulin antihyperglycemic agents to insulin for glycaemic control. Folic Acid 5 mg/d: 3 months pre-conception to 12 weeks post-conception. Discontinue potential embryopathic meds: ACE-inhibitors/ARB (prior to or upon detection of pregnancy) Statin therapy Women who also have PCOS may continue metformin for ovulation induction. Achieving a healthy weight is essential – obesity is associated with adverse pregnancy outcomes.

35. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management Contraception

36. Management of Gestational Diabetes Screening controversy continues whether screening should be universal or selective, based on risk factors ADA’s Fourth international workshop on GDM in 1997 recommended selective screening. the high risk racial groups like India warrant universal screening Screening is done with Oral Glucose test depending on the risk associated

37. Risk assessment for Screening

38. Management of Gestational Diabetes  Screening  The two recommended methods of screening for GDM are:- One Step approach (IADPSG & ADA recommended) Using 75gm of glucose Two step approach (ACOG & NDD group recommended) Using 50gm glucose followed by 100gm

39. Screen i ng  One Step OGT  Two step OGTT 75 gm of glucose at 24-28 wks Fasting ≥ 92 mg/dl 1h PP ≥ 180 mg/dl 2h pp ≥ 153 mg/dl 50 gm of glucose at 24-28 wks 1h PP ≥ 140 mg/dl 100 gm of glucose at 24-28 wks

40. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management Contraception

41. Management of Pregestational Diabetes Glycaemic control during pregnancy Encourage patients to SMBG pre- and postprandial. Pre-conception goals include (ADA) Fasting and pre-meal glucose levels of 80-110 mg/dl 2hr post prandial glucose 100-129mg/dl HbA1c <7% Avoid hypoglycemia. If not controlled by diet or lifestyle modification then pharmacological therapy is initiated, especially for GDM.

42. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management

43. Nutrition Therapy General Dietary Guidelines Appropriate weight gain through carbohydrate and caloric modifications based on height, weight, and degree of glucose intolerance. The mix of carbohydrate, protein, and fat is adjusted to meet the metabolic goals. Daily calorie requirement 1800 kcal-2100 kcal 175-g minimum of carbohydrate per day divided into three meals and 2-4 snacks is to be taken. An ideal dietary composition is 55 % carbohydrate, 20 % protein 25 % fat, of which < 10 % is saturated fat. Weight loss is not recommended, but modest caloric restriction ( 33% ) may be appropriate for overweight or obese women. Avoid severe restriction - <1500 kcal not recommended

44. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management Contraception

45. Diabetes in Pregnancy: management Physical Activity in GDM Improves peripheral insulin resistance and glucose levels Obviate need for insulin Encouraged for women with no obstetric contraindications Cautious not to cause ketosis.

46. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetric management and planning of delivery Post partum follow-up and management Contraception

47. Initiating and maintaining pharmacological therapy The pharmacological therapy available for managing diabetes with pregnancy has been historically Insulin, but recent trends showed that Oral Hypoglycemic drugs are also equally effective especially in cases of Gestational GDM. The OHA recommended are Metformin and Glyburide. According to ACOG OHA can be recommended in GDM but in case of Pregestational diabetes, Insulin is still the pharmacological therapy of choice.

48. Initiating and maintaining pharmacological therapy Insulin is essential if diet control and exercise fail to achieve euglycemia. The requirement of Insulin is different for Pregestational and Gestational diabetes. ACOG recommends multiple daily insulin injections and calorie modifications for Overt Diabetes Whereas for GDM ACOG recommends insulin if: Fasting levels persistently exceed 95mg/dl 1-hour postprandial levels that persistently exceed 140 mg/dL 2-hour levels above 120 mg/dL

49. Initiating and maintaining insulin therapy Insulin Preparations Action Name Onset Durati o n Very rapid Lispro/Novo rapid 10-15mins 2-3 hrs Rapid Crystalline Zinc (CZI) 30-45mins 4-6 hrs Intermediate Neutral Protamine Hagedom (NPH) Lente Zinc 1-2 hrs 6-12 hrs Long acting • Ultralente Zinc Lantus (Glargine) 6-8 hrs 4-8 hrs 18 hrs 24 hrs NPH (80%)+ CZI (20%) 30-45mins 6-12 hrs Premixed • NPH (70%)+ CZI (30%) 30-45mins 6-12 hrs NPH (50%)+ CZI (50%) 30-45mins 6-12 hrs

50. Initiating and maintaining insulin therapy During the first trimester, there is no difference in insulin requirement between type 1 and type 2 subjects. But type 2 DM patients require a significantly higher dose of insulin during 2 nd trimester(33% increase compared to 10% for type I DM) and in 3 rd trimester requirement may be raised up to 40%. This is attributed to the sudden increase in body mass and heightened insulin resistance in type 2 diabetes women during pregnancy. Increased insulin requirement is inevitable in pregnant women with type 2 DM and if not increased in spite of the advancing pregnancy in certain cases, it is a cause of concern. This could be due to poor placental growth, intrauterine growth retardation, and impending intrauterine death. Proactive identification of the cause is needed.

51. Insulin requirement in Overt DM

52. Initiating and maintaining insulin therapy Adjusting insulin doses is simpler with self- monitoring of blood glucose (SMBG) 4 times a day because each component of the insulin regimen affects only 1 SMBG value. The 4 parameters measured are: Fasting blood sugar Post-lunch or PP Pre-dinner Post dinner Measurement should be done atleast after 48 hours of insulin dose adjustment

53. Initiating and maintaining insulin therapy The total dose of required for a pregnant lady is calculated according to the patient’s weight as follows: In the first trimester .......... weight x 0.7/day In the second trimester........ weight x 0.8/day In the third trimester........... weight x 0.9/day This total dose is divided into 2 doses 2/3 in morning 1/3 in evening For tight control “SPLIT REGIMEN” ½ dose divided into 3 parts ½ dose at night In patients who are not well controlled, a brief period of hospitalization is often necessary for the initiation of therapy. Individual adjustments to the regimens implemented can then be made.

54. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetrics management and planning of delivery Post partum follow-up and management

55. Obstetrics management and planning of delivery In view of the threat of late-pregnancy fetal death in women with diabetes, ACOG recommends various fetal surveillance testing at 32-34 weeks. They include F etal movement count Periodic fetal heart rate monitoring Intermittent bio-physical profile Contraction stress testing Mothers are instructed to perform fetal kick counts early in the 3 rd trimester. At 34weeks all insulin treated mothers are preferably admitted and daily fetal movement counts and FHR monitoring is done thrice a week. Delivery is planned at 38weeks.

56. Obstetrics management and planning of delivery For women with gestational diabetes who do not require insulin, early delivery or other interventions are seldom required. Women with gestational diabetes and adequate glycemic control are managed expectantly. Elective induction of labor to prevent shoulder dystocia may be done. Elective cesarean delivery should be done if fetal weight is atleast 4500gms. To avoid brachial plexus injury.

57. Obstetrics management and planning of delivery During labor, continuous fetal heart rate monitoring is mandatory. Labor is allowed to progress as long as normal rates of cervical dilatation and descent are documented. Arrest of dilatation or descent despite adequate labor should alert the physician to the possibility of cephalo pelvic disproportion. Induction of labour is considered if: Multipara with good obstretic history Young primigravidae without any obstetric abnormality Presence of cong. Malformation of fetus.

58. Obstetrics management and planning of delivery

59. Obstetrics management and planning of delivery Insulin management during Section Section should be preferably done early morning. Patient should be kept Nil Orally Morning Insulin dose should be omitted. 5% dextrose with 10 units soluble insulin until pt is able to take fluids by mouth. Epidural or spinal anesthesia preferred than GA as oral feeding can be started soon. Monitoring of glucose level is done hourly. Insullin requirements suddenly falls following the delivery.

60. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetrics management and planning of delivery Post partum follow-up and management Contraception

61. Post partum follow-up and management 50% of the women with GDM may develop overt diabetes within 20years. Women diagnosed with gestational diabetes should undergo evaluation with a 75-g oral glucose tolerance test at 6 to 12 weeks postpartum and at least every 3yrs thereafter. Recurrent GDM: 40% of women with GDM tend to develop it again in subsequent pregnancies and obese women have a greater propensity.

62. Post partum follow-up and management

63. Lactation and Nutrition Breastfeeding is recommended Decreased risk of type 1 diabetes and infection in infant Decrease incidence of type 2 by half. Promotes infant growth and development Maintain pregnancy meal plan or develop postpartum plan to meet added caloric requirements of breastfeeding Rapid weight loss is not advised; exercise is recommended Insulin use must be continued if postpartum euglycemia cannot be maintained with MNT Women with previous GDM 40% to 60% risk of developing type 2 diabetes in 5 to

64. Diabetes in Pregnancy: management Preconceptional counseling Screening Achieving glycaemic targets Nutritional counseling from an Registered Dietitian Encouraging physical activity (avoiding ketosis) Initiating and maintaining pharmacological therapy Obstetrics management and planning of delivery Post partum follow-up and management Contraception

65. Contraception Type % Effectiveness Acceptability Notes Oral co n tracept i on 94–98 + Use preparations with < 0.35-mg estrogen Norplant Depo-Provera 96–99 – May increase insulin needs and/or lower glucose tolerance Barrier methods 72–88 + High failure rates I n traute r i n e devices 97 + Risk of infection no higher with diabetes Rhythm 80 – Menstrual irregularity may lead to failure Tubal ligation 99+ + Potentially irreversible Adapted from Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:21-28

66. Co n clusion Diabetes in pregnancy is a common problem . Risk stratification and screening is essential in almost all pregnant women Tight glycemic targets are required for optimal maternal and fetal outcome Patient education is essential to meet these targets Long term follow up of the mother and baby is essential The timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycemia in them and ensuring adequate nutrition may prevent in all