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Gestational diabetes mellitus dr. sandesh, dr anupama, dr sundar

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Gestational Diabetes Mellitus

Gestational Diabetes Mellitus

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  • Even though gestational diabetes is, by definition, diabetes diagnosed during pregnancy, sometimes blood glucose levels do not return to normal after delivery. Even if glucose levels do return to normal after pregnancy, a history of gestational diabetes (hGDM) has a lifelong impact on the mother’s risk for developing diabetes. Immediately after pregnancy, 5% to 10% of women with gestational diabetes are found to have diabetes, usually type 2.Women who had GDM have a 35% to 60% chance of developing diabetes in the 10 to 20 years after delivery.Children of GDM pregnancies may be at greater future risk for obesity and diabetes.Also, the risk for cardiovascular disease is increased in women with a history of GDM. Studies in women with prior GDM suggest that a chronic inflammatory response may be present and represents an early feature of the cluster of CVD risk factors that relate to insulin resistance and the metabolic syndrome. The good news is there are steps a woman can take to prevent or delay diabetes and lower that risk for both herself and her child. And we learned this from the Diabetes Prevention Program or D-P-P which was sponsored by NIH. Buchanan TA, Xiang A, Kjos SL, Watanabe R: What is gestational diabetes? Diabetes Care 2007; 30 Suppl 2: S105-11.Kitzmiller JL, Dang-Kilduff L, Taslimi MM: Gestational diabetes after delivery. Short-term management and long-term risks. Diabetes Care 2007; 30 Suppl 2: S225-35.

Transcript

  • 1. Diabet es in Pregna ncy Dr. Sandesh Dr. Anupama Dr. Sundar
  • 2. Presentation Outline • Glucose Metabolism • Introduction • Epidemiology • White Classification • Maternal, fetal and infant risks • Screening criteria • Diagnostic criteria • Management Issues • Kathmandu declaration
  • 3. Objectives • To discuss in brief about Gestational Diabetes Mellitus with maternal and fetal effect • To discuss about screening and diagnosis of Gestational Diabetes Mellitus • To discuss about treatment of Gestational Diabetes Mellitus
  • 4. Diabetes mellitus State of carbohydrate intolerance resulting from inadequacy of insulin secretion or ineffectiveness of insulin action.
  • 5. Gestational diabetes Refers to Carbohydrate intolerance resulting in hyperglycemia of variable severity with onset or first recognition during pregnancy irrespective of need for insulin and regardless of whether diabetes persists after pregnancy.
  • 6. Carbohydrate Metabolism and Pregnancy Dr. Sundar 2013-8-27 6
  • 7. • 51 amino acids • 2 chains linked by disulfide bonds • 5800 Dalton molecular weight
  • 8. Effects of Insulin • Nearly all cells (80%) increase glucose uptake (seconds) – Active transport – Primarily affects liver and muscle – Brain tissue is excepted • Alters phosphorylation of many key intracellular metabolic enzymes (minutes) • Alters protein synthesis and gene transcription (hours)
  • 9. Insulin and Fat Metabolism • Liver cells store glycogen only up to 5-6% – Remaining glucose metabolized to fat – Triglycerides are synthesized and release into blood • Adipose cells store fat – Inhibits breakdown of triglycerides – Stimulates uptake and use of glucose to form glycerol – Stimulates fatty acid uptake and conversion to triglycerides • Lack of insulin – Free fatty acids build up in blood – Liver metabolizes to produce phospholipids and cholesterol – Can lead to excess acetoacetic acid production and buildup of acetone (acidosis, which can lead to blindness and coma)
  • 10. Insulin and Protein Metabolism • Promotes – Transport of amino acids – Protein synthesis – Gene transcription • Inhibits protein degradation • Prevents glucose synthesis in liver – Preserves amino acids • Lack of insulin causes elimination of protein stores
  • 11. Insulin Control Muscle Glucose uptake Glycogen synthesis Liver Glucose uptake Glycogen synthesis Fatty acid synthesis Glucose synthesis Brain No effect Pancreas Beta cells Gastrointestinal hormones Feedback amino acids glucose triglyceridesAdipose Glucose uptake Glycerol production Triglyceride breakdown Triglyceride synthesisInsulin Most Cells Protein synthesis Amino acids Blood glucose
  • 12. Effects of Glucagon • Prevents hypoglycemia – Powerful system to degrade glycogen – Increases glucose synthesis from amino acids • Increases with exercise independent of blood glucose • Exerts effects through cAMP second messenger system
  • 13. Insulin Affects Tissues Differently • Muscle – Uptake of glucose and immediate use (exercise) or storage as glycogen (Exercising muscles can take up glucose without insulin) • Liver – Uptake of glucose and storage as glycogen • Inhibits glycogen phosphorylase • Activates glycogen synthase • Inhibits glucose synthesis • Promotes excess glucose conversion to fatty acids • Adipose Tissue – Promotes glucose uptake and conversion to glycerol for fat production
  • 14. Pregnancy and glucose metabolism 2013-8-27 24
  • 15.  Normal pregnancy is characterized by mild fasting hypoglycemia, postprandial hyperglycemia, and hyperinsulinemia.  Increased basal level of plasma insulin in normal pregnancy is associated with several unique responses to glucose ingestion.  Insulin sensitivity in late normal pregnancy is 45 to 70 percent lower than that of nonpregnant women (Butte, 2000; Freemark, 2006). 2013-8-27 25 Carbohydrate metabolism
  • 16. • Deterioration of glucose tolerance occurs normally during pregnancy. • Significant metabolic changes are necessary to provide proper energy delivery to the growing conceptus. 2013-8-27 26 Carbohydrate metabolism
  • 17. • The mechanism(s) responsible for insulin resistance is not completely understood. • Progesterone and estrogen may act, directly or indirectly, to mediate this resistance. • Rising serum levels of estrogen and progesterone increase insulin production and secretion while increasing tissue sensitivity to insulin. 2013-8-27 27 Carbohydrate metabolism
  • 18. • Plasma levels of placental lactogen increase with gestation, and this protein hormone is characterized by growth hormone–like action that may result in increased lipolysis with liberation of free fatty acids (Freinkel, 1980). • The increased concentration of circulating free fatty acids also may aid increased tissue resistance to insulin (Freemark, 2006). 2013-8-27 28 Carbohydrate metabolism
  • 19. Glucose Metabolism in Pregnancy • Fetal growth is dependent upon maternal glucose • Carbohydrates from maternal diet • Stored glycogen converted to glucose • High levels of glucose transported by diffusion to the fetus • Fetal production of insulin
  • 20. 1st Trimester • The overall result is a lowering of the fasting glucose levels, reaching a nadir by the 12th week. • The decrease is on average 15 mg/dL; thus fasting values of 70-80 mg/dL are normal in a pregnant woman by the 10th week of gestation. 2013-8-27 30
  • 21. 2nd Trimester • In the second trimester, higher fasting and postprandial glucose levels are seen. This facilitates the placental transfer of glucose. • Glucose transfer is via a carrier-mediated active transport system that becomes saturated at 250 mg/dL. 2013-8-27 31
  • 22. 2nd Trimester (contd) • Fetal glucose levels are 80% of maternal values. In contrast, maternal amino acid levels are lowered during the second trimester by active placental transfer to the fetus. • Fetal levels of amino acids are 2- to 3-fold higher than maternal levels, but not as high as levels within the placenta. • Lipid metabolism in the second trimester shows continued storage until midgestation; then, as fetal demands increase, there is enhanced mobilization (lipolysis). 2013-8-27 32
  • 23. Physiology in Late Pregnancy Characterized by accelerated growth of the fetus • A rise in blood levels of several diabetogenic hormones • Food ingestion results in higher and more prolonged plasma glucose concentration
  • 24. Physiology in Late Pregnancy • Maternal insulin and glucagon do not cross the placenta • During late pregnancy a women’s basal insulin levels are higher than non-gravid levels • Food ingestion results in a twofold to threefold increase in insulin secretion (Franz, M.J., 2001)
  • 25. Physiology of GDM • Gestational hormones induce insulin resistance • Inadequate insulin reserve and hyperglycemia ensues
  • 26. ‘Endocrinology of Pregnancy’ • The placenta produces larger quantities of more hormones than any other human organ: – Human placental lactogen – Estrogen / progesterone • The majority of its products are released into the maternal circulation to induce changes on the fetuses’ behalf.
  • 27. HPL • HPL is the hormone mainly responsible for insulin resistance and lipolysis. • HPL also decreases the hunger sensation and diverts maternal carbohydrate metabolism to fat metabolism in the third trimester. • HPL is a single-chain polypeptide secreted by the syncytotrophoblast and has a molecular weight of 22,308 and a half-life of 17 minutes. • HPL levels are elevated during hypoglycaemia to mobilize free fatty acids for energy for maternal metabolism. 2013-8-27 37
  • 28. HPL (cont) • During pregnancy, the levels of HPL rise steadily during the first and second trimesters with a plateau in the late third trimester. • This plateau is the natural result of decreasing nutrient delivery to the placenta, thus decreasing hormone production. 2013-8-27 38
  • 29. Cortisol • Cortisol levels rise during pregnancy and stimulate endogenous glucose production and glycogen storage and decrease glucose utilization. 2013-8-27 39
  • 30. Prolactin • Prolactin levels are also increased 5- to 10-fold • may have an impact on carbohydrate metabolism. • patients with hyperprolactinemia deserve early pregnancy glucose screening. 2013-8-27 40
  • 31. Dr. Anupama Epidemiology and management
  • 32. Epidemiology • Abnormal maternal glucose regulation occurs in 3-10% of pregnancy. • DOUBLES the risk of serious injury at birth, TRIPLES the likelihood of caesarean delivery and QUADRUPLES the incidence of newborn intensive care unit admission (eMed.Journal, June 2000 , Vol 3, Number 6)
  • 33. Epidemiology • The prevalence of GDM in low-risk populations ranges from 1.4% to 2.8%; in high-risk populations, prevalence ranges from 3.3% to 6.1% • Abnormal maternal glucose regulation occurs in 3-10% of pregnancy. • Prevalence different among different races and population
  • 34. Approximate Prevalence of Diabetes in Pregnancy in the United States GDM=gestational diabetes mellitus Nondiabetes 92% More than 200,000 type 2 diabetes mellitus + 135,000 GDM + 6000 type 1 diabetes mellitus = 341,000 pregnancies complicated by hyperglycemia annually Diabetes 8% 4.022 Million Births in 2002 50% GDM Diabetes 8% 2% T1DM 24% Diagnosed T2DM
  • 35. • GDM represents 90% of all cases of diabetes mellitus that are diagnosed during pregnancy. • Compared to European women, prevalence of gestational diabetes has increased eleven fold in women from the Indian subcontinent . • DOUBLES the risk of serious injury at birth, TRIPLES the likelihood of caesarean delivery and QUADRUPLES the incidence of newborn intensive care unit admission (eMed.Journal, June 2000 , Vol 3, Number 6)
  • 36. Diabetes in Nepal • Singh and Bhattarai found the rates of DM and IGT to be 14.6 and 9.1% in urban areas, and 2.5 and 1.3% in rural areas [Diabet. Med. 20 (2003) 170–171] • Prevalence more in urban population than in the rural population [Diabet. Med. 20 (2003) 170–171] • Most of the Nepalese Diabetic patients have poor KAP scores [Rawal Medical Journal.2008; 33(1):8-11] • No published studies about prevalence of GDM in Nepal
  • 37. Importance Pregnant women with pre-gestational diabetes are at higher risk for multiple complications affecting both the mother and the fetus than those women without diabetes Obstet Gynecol 2003;101: 380-392.
  • 38. White Classification of Diabetes Mellitus in Pregnancy GDM: • Class A1 Gestational diabetes (GDM) not requiring insulin (or oral agents). • Class A2 Gestational diabetes requiring insulin (or oral agents). Pregestational DM: • Class B Onset at >20 years of age or duration of <10 years. • Class C Onset at 10 to 19 years of age or duration of 10 to 19 years, no vascular disease.
  • 39. Cont.. • Class D Onset at <10 years of age or duration of 20 years or more or, any onset/duration but with background retinopathy or hypertension only. • Class F Nephropathy (>500 mg proteinuria per day at <20 weeks of pregnancy). • Class H Arteriosclerotic heart disease, clinically evident. • Class R Proliferative diabetic retinopathy (active) or vitreous hemorrhage. • Class T History of renal transplant
  • 40. Causes of GDM • Inadequate insulin production • Increased insulin resistance Or Both!! • Strong genetic predisposition • Progressive increased risk until term (but most clinically significant problems are evident by the early third trimester)
  • 41. GDM Risk Factors:  Family history  Previous child > 9 pounds  Glycosuria  Previous stillbirth – fetal anomalies - polyhydramnios  Maternal age (>30)  Non-Caucasian  Obesity
  • 42. Low-risk status requires no glucose testing, but this category is limited to those women meeting all of the following characteristics:  Age <25 years.  Weight normal before pregnancy .  Member of an ethnic group with a low prevalence of gestational diabetes mellitus .  No known diabetes in first-degree relatives .  No history of abnormal glucose tolerance .  No history of poor obstetric outcome . Risk assessment
  • 43. Intermediate risk for GDM • Patients with any one of the following – Ethnic population except Caucasian, European – Age > 25 – BMI > 25 • with – No known diabetes in first degree relative – No H/O glucose intolerance – No H/O obstetric complications usually associated with GDM 5th International Workshop- Conference on Gestational Diabetes Mellitus, ADA, ACOG
  • 44. Risk assessment marked obesity. personal history of gestational diabetes mellitus. Glycosuria. a strong family history of diabetes . A high risk of gestational diabetes mellitus:
  • 45. • high risk patients should undergo glucose testing A fasting plasma glucose level >125mg/dL or a casual plasma glucose >200 mg/dL meets the threshold for the diagnosis of diabetes In the absence of this degree of hyperglycemia, evaluation for gestational diabetes mellitus in women with average or high-risk characteristics is by glucose tolerance test . Risk assessment
  • 46. Screening • Screening commonly conducted during the 24th to 28th week of gestation • Using the 140 mg/dl threshold, the GCT is positive for 14% to 18% of all pregnant women, including about 80% of women with GDM
  • 47. Current recommendations for screening • High risk patients should be screened as early as possible and repeated at 24-28 weeks if screening negative – Strong family history of diabetes – Prior history of GDM – Morbid obesity – Other manifestations of glucose intolerance 5th International Workshop- Conference on Gestational Diabetes Mellitus, ADA, ACOG
  • 48. • 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 diagnostic 3-hr 100-g OGTT • Glucose challenge test: – Venous plasma glucose level is measured after 1 hr of 50 gm glucose load without regard to time of day and time of last meal. • Threshold value for 1-hr GCT is 130 or 140mg/dl – either is acceptable Current recommendations for screening for GDM 5th International Workshop- Conference on Gestational Diabetes Mellitus, ADA, ACOG
  • 49. 50-g oral glucose challenge The screening test for GDM, a 50-g oral glucose challenge, may be performed in the fasting or fed state. Sensitivity is improved if the test is performed in the fasting state . A plasma value above 130-140 mg one hour after is commonly used as a threshold for performing a 3- hour OGTT. If initial screening is negative, repeat testing is performed at 24 to 28 weeks.
  • 50. Threshold 130mg/dl 140mg/dl Sensitivity 90% 80% False positives 20-25% 14-18% WHO advocates universal screening utilizing a one- step 2-hr 75-g OGTT
  • 51. 75 gm 2-Hour OGTT Fasting 95 mg% 1-hour 180 mg% 2-hour 155 mg%
  • 52. 3 hour Oral glucose tolerance test Prerequisites: - Normal diet for 3 days before the test. - No diuretics 10 days before. - At least 10 hours fast. - Test is done in the morning at rest. Giving 75 gm (100 gm by other authors) glucose in 250 ml water orally Criteria for glucose tolerance test: The maximum blood glucose values during pregnancy: - fasting 90 mg/ dl, - one hour 165 mg/dl, - 2 hours 145 mg/dl, - 3 hours 125 mg/dl. If any 2 or more of these values are elevated, the patient is considered to have an impaired glucose tolerance test.
  • 53. Diagnosis of GDM with a 100-g or 75-g glucose load 100 gm Glucose load mg/dl mmol/L Fasting 95 5.3 1 hr 180 10.0 2 hr 155 8.6 3 hr 140 7.8 75 gm glucose load Fasting 95 5.3 1 hr 180 10.0 2 hr 155 8.6 Two or more of the venous plasma concentrations must be met or exceeded for a positive diagnosis. The test should be done in the morning after an overnight fast of between 8 and 14 h and after at least 3 days of unrestricted diet (≥150 g carbohydrate per day) and unlimited physical activity. The subject should remain seated and should not smoke throughout the test. Diabetic care
  • 54. GDM Criteria National Diabetes Data Group* American Diabetes Association* World health Organization † Carpenter and Coustan* Fasting 105 95 ≥ 126 95 1 hour 190 180 - 180 2 hours 165 155 ≥ 140 155 3 hours 145 - 140 *2 or more criteria met = positive diagnosis (cutoff points in mg/dl) † 1 or more criteria met = positive diagnosis
  • 55. A POSITIVE SCREEN DOES NOT ESTABLISH THE DIAGNOSIS OF GESTATIONAL DIABETES!!!
  • 56. Adverse Pregnancy Outcomes • Maternal risks: – Pre-eclampsia: affects 10-25% of diabetic pregnancies. – Increased operative vaginal deliveries and consequent trauma – polyhydramnios – Increased C-section – PPH: due to overdistension of uterus – Infection: due to chorioamnionitis and post partum endometritis – >50% of women with gestational diabetesn will develop overt DM in ensuing 20 yrs – Recurrence rate: 35-50%
  • 57. Potential Complications in Infants of Mothers With Diabetes • Intrauterine demise – Spontaneous abortion – Stillbirth • Macrosomia • Visceromegaly – Cardiomegaly – Hepatic enlargement • Birth injury – Shoulder dystocia – Erb’s palsy – Diaphragmatic paralysis – Facial paralysis – Cerebral ischemia – Hemorrhage in brain, eyes, liver, genitalia Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:133-149
  • 58. – Macrosomia: • Birth weight >4500gm (ACOG) • Occurs in 17-29% of gestational diabetes(ACOG: 12%) • Patho physiology: maternal hyperglycemia Fetal hyperglycemia Fetal hyperinsulinemia Excess somatic growth • Consequent complications: – Shoulder dystocia. Brachial plexus injury, clavicular fracture – Risk of fetal anomalies and fetal death more in overt diabetes
  • 59. • Cardiac( including great vessel anomalies) : most common • Central nervous system: 7.2% • Skeletal: cleft lip/palate, caudal regression syndrome • Genitourinary tract: ureteric duplication • Gastrointestinal : anorectal atresia Fetal congenital anomalies
  • 60. • Neonatal risks: – Hypoglycemia – Hypocalcemia – hypomagnesemia – Hyperviscosity syndrome due to polycythemia – Hyperbilirubinemia – Respiratory distress syndrome – Cardiomyopathy
  • 61. Pedersen Hypothesis (1952) • Maternal hyperglycemia  • Fetal hyperglycemia  • Fetal hyperinsulinemia  • Excess fetal fat
  • 62. Fetal hyperinsulinemia The Impact of Maternal Hyperglycemia During Pregnancy Modified Pedersen Hypothesis Fetus Fetal pancreas stimulated IgG=immunoglobulin G MotherPlacenta IgG-antibody-bound insulin Insulin Maternal hyperglycemia Insulin resistance syndrome
  • 63. Monitoring Urine glucose monitoring is not useful in gestational diabetes mellitus. Urine ketone monitoring may be useful in detecting insufficient caloric or carbohydrate intake in women treated with calorie restriction.
  • 64. Daily self-monitoring of blood glucose (SMBG) appears to be superior to intermittent office monitoring of plasma glucose. Monitoring
  • 65. For women treated with insulin, preprandial monitoring is superior to postprandial monitoring. However, the success of either approach depends on the glycemic targets that are set and achieved. Monitoring
  • 66. Glycosylated haemoglobin (Hb A1 It is normally accounts for 5-6% of the total haemoglobin mass. A value over 10% indicates poor diabetes control in the previous 4-8 weeks. If this is detected early in pregnancy, there is a high risk of congenital anomalies . If this is detected in late pregnancy it indicates increased incidence of macrosomia and neonatal morbidity and mortality. Monitoring
  • 67. The mean glucose represented by the hemoglobin A1c level can be calculated using the "rule of 8's." A value of 8 percent equals 180 mg/dl, and each 1 percent increase or decrease represents ± 30 mg/dl. Glycosylated haemoglobin (Hb A1 Monitoring
  • 68. Assessment for asymmetric fetal growth by ultrasonography, particularly in early third trimester, may aid in identifying fetuses that can benefit from maternal insulin therapy Monitoring
  • 69. Maternal surveillance should include blood pressure and urine protein monitoring to detect hypertensive disorders. Monitoring
  • 70. Goals of management • Achieving glycemic targets • Nutritional counseling from an Registered Dietitian • Encouraging physical activity • Avoiding ketosis • Initiating and maintaining insulin therapy • Arrangement and planning of delivery • Post partum follow-up and management
  • 71. 2 groups of patients • Pregnant ladies with established diabetes (type I or type II) • Pregnant ladies with new onset diabetes (GDM)
  • 72. • SMBG (self-monitoring of blood glucose) – Fasting/premeal: 80 to110 mg/dL – 1 hour postmeal: <155 mg/dL • HbA1C – In normal range (<6%, but ideally <5%) – Target value of HbA1C is stable at <7 Preconception Care of Established Diabetes Joslin Diabetes Center and Joslin Clinic; Guideline for Detection and Management of Diabetes in Pregnancy 9/14/2005
  • 73. Medical Goals • Switch from oral agent therapy to physiologic basal-bolus insulin replacement (type 2 diabetes) • Prevent hypoglycemia and ketoacidosis • Blood pressure <130/80 mm Hg • Protein excretion levels <150 mg/24 hours • Free T4 >1.0 but <1.6 ng/dL TSH <2.5 IU/mL • Establish medical team for ongoing management Preconception Care of Established Diabetes American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S76-S78
  • 74. Exception to discontinuing oral anti-diabetic medication during pregnancy Metformin may be continued during first trimester on patients with PCOS or type 2 DM with anovulatory infertility At first visit should begin increasing insulin to control blood sugar and taper off metformin
  • 75. What about other medications!!! • Gliburide • Other OHA’s • ACE inhibitors • ARBs • All cholesterol lowering agents.
  • 76. Booking Antenatal visit for existing Diabetic Patients • HbA1C • 24 hr urine (protein, creatinine clearance, creatinine) • EKG • Eye examination • Renal function tests (Class D-T) • Dating scan at 10 – 12 weeks
  • 77. GDM Screening and Diagnosis Universal Screening Guidelines Average and high risk: Screen at intake Low risk: Screen at 24 to 28 weeks’ gestation Screen with 1-h 50-g GCT 180 mg/dL STOP Check Fasting BS >95 Diabetic Refer to HEd, A1C 140–180 mg/dL Administer FPG and 3-h 100-g OGTT on separate day 130 mg/dL STOP Patient does not have GDM If FPG 95 mg/dL STOP Patient has GDM Refer to Health Ed Otherwise, administer 3-h 100-g OGTT (2 or more abnormal values, patient has GDM) 1 h 180 mg/dL 2 h 155 mg/dL 3 h 140 mg/dL If patient has GDM risk factors, rescreen at 24–28 weeks’ gestation Rescreen later in gestation FPG=fasting plasma glucose Jovanovic-Peterson L et al. Am J Perinatol. 1997;14:221-228 /ADA 2006 Diabetes Care
  • 78. SMBG –Pregnancy Complicated by Diabetes Blood Glucose Goals and Testing Frequency Goal Timing Fasting 60–90 mg/dL Test on waking from bed Pre-meal 60–90 mg/dL Test before each meal 1-hour postprandial 2-hour postprandial 100–130 mg/dL 100-120 mg/dl Test 1 hour after each meal screens for highest sugar exposure to fetus. Some Perinatologist prefer 2 hour Postprandial check 11:00 PM–4:00 AM 60–100 mg/dL Test at bedtime or in middle of the night* *2:00–4:00 AM if nocturnal hypoglycemia is suspected
  • 79. • 3 daily meals; snack as needed • Small breakfast • Control of carbohydrate intake; – low glycemic foods. Minimal 130 grams of CHO. • High fiber diet • Foods with low saturated fat • Avoiding concentrated sweets • multivitamin with iron, folic acid, and calcium Nutrition Therapy General Dietary Guidelines
  • 80. Physical Activity in GDM • Improves peripheral insulin resistance and glucose levels • Obviate need for insulin • Encouraged for women with no obstetric contraindications Jovanovic-Peterson L et al. Am J Obstet Gynecol. 1989;161:415-419
  • 81. Energy requirement 25 years female IBW 60 kg Carbohydrate (65%) 450 Protein (10%) 70 Fat (25%) 180 Carbohydrate 100 gm Protein (10%) 15 gm Fat (25%) 17 gm Diet Carbohy. Protein Fat _ Arabian bread 30 gm --- --- Cheese 5 gm 10 gm 10 gm Honey 50 gm 2 gm 3 gm Glass of milk 10 gm 5 gm 5 gm_ Total 95 gm 17 gm 18 gm Carbohydrate (65%) 590 Protein (10%) 90 Fat (25%) 220 Carbohydrate 130 gm Protein (10%) 20 gm Fat (25%) 22 gm Diet Carbohy. Protein Fat _ Rice 80 gm --- 6 gm chicken 5 gm 15 gm 12 gm Salad 30 gm 4 gm 4 gm Orange 10 gm --- ---___ Total 125 gm 19 gm 22 gm Carbohydrate (65%) 330 Protein (10%) 50 Fat (25%) 120 Carbohydrate 65 gm Protein (10%) 10 gm Fat (25%) 11 gm Diet Carbohy. Protein Fat _ Tuna sandwich 45 gm 12 gm 10 gm Apple 15 gm --- --- Tea --- --- --- _ Total 95 gm 17 gm 18 gm 60 Kg X 30 kcal = 1800 kcal with 30% extra= 2100 Kcal Breakfast 700 kcal Lunch 900 kcal Dinner 500 kcal
  • 82. Grains – 8-10 choices Fruit – 2-3 choices Milk – 3-4 choices
  • 83. Avoid severe restriction - <1500 kcal not recommended Avoid excessive fatty foods 33% calorie restriction slowed wt gain and improved BG 1800 kcal-2100 kcal
  • 84. • Fasting venous plasma < 95 mg/dl • 2 hour postprandial <120 mg/dl • 1 hour postprandial <130 mg/dl (140) • Pre-meal and bedtime: 60 to 95 mg/dl Glycemic targets ACOG recommendation If diet therapy fails to maintain these targets > 2 times/week, start insulin These are venous plasma targets, not glucometer targets
  • 85. Why these tight glycemic targets? Prospective study in type1 patients with pregnancy FBS Macrosomia >105 mg/dl 28.6 % 95-105 10% <95 mg/dl 3%
  • 86. GDM Failure to maintain glycemic targets INSULIN THERAPY Medical nutrition therapy
  • 87. Can OHA be used to treat GDM? • Glyburide – Does not cross the placenta – Controlled BG in 80% of women – Women with high FBG less likely to respond to Glyburide – More adverse perinatal outcomes compared to insulin – use is considered off-label and requires appropriate discussions of risks with patient
  • 88. Metformin – alone or with insulin was not associated with increased peri-natal complications compared with insulin – Less severe hypoglycemia in neonates – Does cross the placenta – long term study MiG TOFU ongoing – use is considered off-label and requires appropriate discussions of risks with patient (NEJM, 2008) Contd…
  • 89. Metformin in GDM • Metformin versus Insulin for the Treatment of Gestational Diabetes751 women with GDM randomly assigned to metformin (with supplemental insulin if needed) or insulin – Metformin group: 92.6% continued until delivery, 46.3% received supplemental insulin – Primary and secondary outcomes were statistically similar – Women preferred metformin to insulin • No studies to compare metformin and glyburide Rowan J. MiG Trial, NEJM, May 2008
  • 90. Insulin • Polypeptide hormone • Secreted by β cells of pancreas • Discovered by Frederick Banting and Charles Best (1921) • Leonard Thompson (age 14, 65lbs) first patient successfully treated.
  • 91. Insulin Preparation Action Name Onset Duration Very rapid Lispro / Novo rapid 10-15 min 2-3 hrs Rapid Crystalline zinc (CZI) 30-45 min 4-6 hrs Intermediate Neutral Protamine Hagedorn (NPH) 1-2 hrs 6-12 hrs Lente zinc Long acting Ultralente zinc 6-8 hrs 18 hrs Lantus (glargine) 4-8 hrs 24 hrs Premixed 80% NPH+20%CZI 30-45 min 6-12 hrs 70% NPH+30%CZI 30-45 min 6-12 hrs 50% NPH+50%CZI 30-45 min 6-12 hrs
  • 92. • Fast acting: Humalog , NovoRapid • Short acting: Regular/R • Intermediate acting: NPH/N – Detemir can be used if woman unable to tolerate NPH ( Ongoing study to evaluate use in pregnancy) – Glargine – avoid use • Human Insulins-Least Immunogenic Breastfeeding mother- All types insulin considered safe Insulin Safety in Pregnancy
  • 93. Insulin types and duration of action 0 3 6 9 12 15 18 21 24
  • 94. 10/90 20/80 30/70 40/60 50/50 time Bloodsugar
  • 95. Insulin Delivery Throughout Pregnancy Daily Insulin Dose for Pregnancy with Preexisting Diabetes Gestational week 4–12 12–24 24–38 38–42 0.7 U 0.8 U 0.9 U 1.0 U Insulin dose Multiplied by current pregnant weight in kg Jovanovic L. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker Inc; 2002:139-151
  • 96. Principles for Insulin • Calculation of total dose required • Divided into 2 doses • 2/3 in morning • 1/3 in evening • NPH + Regular or rapid acting in AM, regular or rapid acting at supper, NPH at bedtime • Regular or rapid acting (lispro or aspart) with meals, NPH at bedtime
  • 97. Alternate Insulin Dosing in GDM • For tight control “SPLIT REGIMEN” • ½ dose divided into 3 parts • ½ dose at night
  • 98. Insulin: when to initiate? Blood glucose ADA ACOG Fasting ≤105 mg/dL >95 mg/dL 1hr pp ≤155 mg/dL 2hr pp ≤130 mg/dL >120 mg/dL
  • 99. The total dose of required for a pregnant lady is calculated according to the patient’s weight as follows: Insulin therapy …..cont. In the first trimester .......... weight x 0.7 In the second trimester........ weight x 0.8 In the third trimester........... weight x 0.9
  • 100. Blood sugar moderately elevated – Mixed insulin started – 50:50 or 30:70 Blood sugar highly elevated – Continuous insulin infusion – Total 24 hour dose identification – After identifying mixed insulin DKA – Continuous insulin infusion
  • 101. Insulin Dose adjustment • 4 parameters measured – Fasting blood sugar – Post-lunch or PP – Pre-dinner – Post dinner • Measurement should be done atleast 48 hours of insulin dose adjustment NEXT
  • 102. • Very high parameter –supplemental regular insulin • Insulin dose readjustment –Depending upon the derangement NEXT Insulin Dose adjustment
  • 103. • High morning levels, but controlled evening levels • Controlled morning levels, but high evening levels • High fasting or pre-dinner, but controlled PP or post dinner • Controlled fasting or pre-dinner, but elevated PP or post dinner • All 4 parameters deranged Insulin Dose adjustment NEXT
  • 104. Insulin Delivery Throughout Pregnancy Initiating Insulin Therapy in GDM • regular insulin based on specific abnormal FPG, pre-meal, and 1-hour postprandial glucose readings – high FPG with bedtime NPH – pre-dinner hyperglycemia with pre-breakfast NPH – bedtime hyperglycemia with pre-dinner NPH – abnormal postprandial glucose with rapid-acting insulin (lispro or aspart) immediately before the offending meal • Evaluate regimen for 1 week; adjust as needed to maintain glucose <90 mg/dL before meals and <120 mg/dL 1 hour post-meal • 1 unit of insulin will neutralize 20 mg/dl of blood sugar Jovanovic L, ed in chief. Medical Management of Pregnancy Complicated by Diabetes. 3rd ed. Alexandria, Va: American Diabetes Association; 2000:111-132
  • 105. Additional units (regular insulin) Preprandial glucose mg/dl 0<100 2100-140 3140-160 4160-180 5180-200 6200-250 8250-300 10>300 supplemental regular insulin scale
  • 106. 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 Hospitalization
  • 107. Clinical pearls • Start with insulin @0.2Units per kg per day • If type I DM need of basal insulin needs to be addressed • If blood sugar highly elevated in GDM or Overt type II DM may start with higher doses • Long acting insulin at bedtime to cover morning fasting • NPH dose must be adjusted based on fasting blood sugars • Lantus offers a more constant basal coverage with less injections
  • 108. Twice daily regimen Hours of day 4:00 16:00 20:00 24:0012:008:00 Plasmainsulin 24:00 Breakfast Lunch Dinner
  • 109. Additional dose during lunch 4 tight control Hours of day 4:00 16:00 20:00 24:0012:008:00 Plasmainsulin 24:00 Breakfast Lunch Dinner
  • 110. Split regimen Regular Insulin before meal and long acting at bedtime Hours of day 4:00 16:00 20:00 24:0012:008:00 Plasmainsulin 24:00 Long act Breakfast Long actLong act Lunch Dinner
  • 111. Insulin Lispro Controls Postprandial Hyperglycemia in GDM Plasma glucose (mg/dL) Jovanovic L et al. Diabetes Care. 1999;22:1422-1427 0 20 40 60 80 100 120 140 0 60 120 180 Time (min) Regular human insulin Insulin lispro
  • 112. Infant Malformations in Preexisting Diabetes Are Related to First-Trimester A1C Levels, Not Type of Insulin A1C standard deviation from mean at first prenatal visit correlates with major anomaly rate in insulin lispro–treated patients (5.4%, P=0.04) Wyatt JW et al. Diabet Med [online early]. Available at: http://www.blackwell-synergy.com/ links/doi/10.1111/j.1464-5491.2004.01498.x/abs/ 0 2 4 6 8 10 12 14 <–2 –2 to <0 0 to <2 2 to <4 4 to <6 6 to <8 8 Percent with major anomalies A1C standard deviation from mean
  • 113. KETOACIDOSIS
  • 114. KETOACIDOSIS • As pregnancy is a state of relative insulin resistance marked by enhanced lipolysis and ketogenesis • diabetic ketoacidosis may develop in a pregnant woman with glucose levels barely exceeding 200 mg/dl • DKA may be diagnosed during pregnancy with minimal hyperglycemia accompanied by a fall in plasma bicarbonate and a pH value less than 7.30
  • 115. clinical signs of volume depletion follow the symptoms of hyperglycemia, which include polydipsia and polyuria. Malaise. Headache.  nausea. Vomiting. KETOACIDOSIS
  • 116. Occasionally, diabetic ketoacidosis may present in an undiagnosed diabetic woman receiving β-mimetic agents to arrest preterm labor Because of the risk of hyperglycemia and diabetic ketoacidosis in diabetic women Terbutaline and magnesium sulfate has become the preferred tocolytic for cases of preterm labor in these cases. Antenatal corticosteroids used to accelerate fetal lung maturation can cause significant maternal hyperglycemia and precipitate DKA KETOACIDOSIS
  • 117. An intravenous insulin infusion will usually be required and is adjusted on the basis of frequent capillary glucose measurements. Therapy hinges on the meticulous correction of metabolic and fluid abnormalities. Every effort should therefore be made to correct maternal condition before intervening and delivering a preterm infant. KETOACIDOSIS
  • 118. ANTEPARTUM FETAL EVALUATION antepartum fetal monitoring tests are now used primarily to reassure the obstetrician and avoid unnecessary premature intervention. These techniques have few false-negative results, allowing the fetus to benefit from further maturation in utero.
  • 119. Ultrasound Ultrasound is a valuable tool in evaluating fetal growth, estimating fetal weight, and detecting hydroamnios and malformations.
  • 120. Ultrasound….cont. Ultrasound examinations should be repeated at 4- to 6-week intervals to assess fetal growth. The detection of fetal macrosomia, the leading risk factor for shoulder dystocia, is important in the selection of patients who are best delivered by cesarean section.
  • 121. The non-stress test (NST • Done weekly from 28 weeks and Twice weekly from 34 weeks • remains the preferred method to assess ante- partum fetal well-being in the patient with diabetes mellitus • If the NST is nonreactive, a biophysical profile (BPP) or contraction stress test is then performed .
  • 122. Doppler umbilical artery velocimetry Doppler umbilical artery velocimetry has been proposed as a clinical tool for antepartum fetal surveillance in pregnancies at risk for placental vascular disease. It is found that Doppler studies of the umbilical artery may be predictive of fetal outcome in diabetic pregnancies complicated by vascular disease. Elevated placental resistance as evidenced by an increased systolic/diastolic ratio is associated with fetal growth restriction and preeclampsia in these high-risk patients.
  • 123. Limited data from a single randomized controlled trial suggest that induction of labour in women with gestational diabetes treated with insulin reduces the risk of macrosomia. The Cochrane Library, Issue 4, 2003
  • 124. When antepartum testing suggests fetal compromise, delivery must be considered.
  • 125. • Delivery by cesarean section usually is favored when fetal distress has been suggested by antepartum heart rate monitoring • Delivery planned at 38 weeks' gestation • elbecause of poor control or a history of a prior stillbirth, an elective delivery is planned
  • 126. 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 cephalopelvic disproportion.
  • 127. Indications: 1) Multipara with good obstretic history 2) Young primigravidae without any obstetric abnormality 3) Presence of cong. Malformation of fetus. Induction of labour:
  • 128. • NO breakfast on the day of induction. • Low rupture of membrane with simultaneous oxytocin drip if no contraindication. • % dextrose with 10 unit soluble insulin @ 100- ml /hr(1-1.25units /hr). • Hourly bld glucose estimation using dextrostix and insulin adjusted accordingly. • If labour fails to start within 6-8 hrs or unsatisfactory progress, Caesarian section. Methods:
  • 129. Low dosage constant insulin infusion for intra partum period: Blood glucose (mg/dl) Insuline dosage (U/hr) Fluids (125ml/hr) <100 0 D5RL 100-140 1.0 D5RL 141-180 1.5 NS 181-220 2.0 NS >220 2.5 NS
  • 130. Indications: 1) Elderly primi 2) Multigravidae with BOH 3) Uncontrolled diabetes 4) Obstetrical complication like pre- eclampsia,polyhydramnioius,malpresentation 5) Large baby Caesarian section:
  • 131. • Perform early morning. • Omit breakfast and insulin dose. • % dextrose with units soluble insulin until pt is able to take fluids by mouth. • Insullin requirements suddenly falls following the delivery. • Epidural or spinal anaesthesia prefferd than GA as oral feeding can be started soon.
  • 132. • Usual dose of intermediate-acting insulin is given at bedtime. • Morning dose of insulin is withheld. • Intravenous infusion of normal saline is begun. • Once active labor begins or glucose levels fall below 70 mg/dl, the infusion is changed from saline to 5% dextrose and delivered at a rate of 2.5 mg/kg/min. • Glucose levels are checked hourly using a portable meter allowing for adjustment in the infusion rate. • Regular (short-acting) insulin in administered by intravenous infusion if glucose levels exceed 140 mg/dl. Insulin Management during Labor and Delivery
  • 133. Scottish A national clinical guideline • Women with insulin-requiring diabetes in pregnancies which are otherwise progressing normally should be assessed at 38 weeks gestation to ensure delivery by 40 weeks. • Women with diabetes should be delivered in consultant- led maternity units which have a senior physican, obstetrician, and neonatologist available. • The progress of labor should be monitored as for other high risk women, including continuous electronic fetal monitoring. • Intravenous insulin and dextrose should be administered as necessary to maintain blood glucose levels between 4 and 7 mmol/l.
  • 134. • During labor close blood glucose monitoring • Adjust dextrose and insulin accordingly • post delivery spontaneos correction of GDM • Screening for hypoglycemia of newborn • Exclussive breast feeding
  • 135. HAPO (Hyperglycemia And Pregnancy Outcomes*) Followed > 23,000 women after a 2-hour 75 gram GTT to determine whether there were glucose value thresholds that separated normal outcomes from complicated outcomes. Women with FBS > 105 or 2-hr glucoses > 200 were unblinded. Followed for BW > 90th percentile, primary cesarean, neonatal hypoglycemia, cord-blood C-peptide > 90th percentile. *NEJM 2008;358:1991-2002
  • 136. HAPO Conclusion • Strong, continuous associations of maternal glucose levels below those diagnostic of GDM were seen with birthweight and increased cord-blood C-peptide levels. • The current criteria for diagnosing and treating hyperglycemia during pregnancy needs to be re-evaluated.
  • 137. ACHOIS (Australian Carbohydrate Intolerance Study) • Randomized 1000 women with 2-hr 75 gram glucose values 140-200 to treatment – no treatment (‘normal < 155). • Treatment group: Fewer serious perinatal complications and lower birth weights but more NICU admissions. • Number needed to treat to prevent a ‘serious complication’ (death, shoulder dystocia, bone fracture, nerve palsy) was 34. • No change in cesarean rate. NEJM 2005;352:2477-86
  • 138. Gestational Diabetes: Post-natal • Blood glucose testing first few days after delivery • Fasting glucose rechecked 6-12 weeks following delivery • Every 6-12 months thereafter to be screened for Type 2 Diabetes-high risk of developing Type 2 Diabetes (7x higher) and/or CVD Kitzmiller, et al Diabetes Care 30:S225-S235, 2007 Diabetes Care 34:Supplement 1, 2011
  • 139. Why is Gestational Diabetes a Concern AFTER Pregnancy • Immediately after pregnancy, 5% to 10% of women with GDM have diabetes, usually type 2. • Women who had hGDM have 35% to 60% chance of developing diabetes in the 10 to 20 years after delivery. • Risk for cardiovascular disease may be increased. • Children of GDM pregnancies may be at greater risk for future obesity and diabetes. Buchanan TA, et al.Diabetes Care 2007; 30 Suppl 2: S105-11. Kitzmiller JL, et al. Diabetes Care 2007; 30 Suppl 2: S225-35.
  • 140. Postpartum Focus: – OGTT (6 weeks to 6 months 75 g OGTT) – weight management, – postpartum visit with a registered dietitian – Encourage breastfeeding – Monitoring occasionally with meter – Future pregnancy
  • 141. Neonatal Hypoglycemia Is Inversely Related to Maternal Hyperglycemia at Delivery 0 50 100 150 200 250 Maternal glucose Neonatal glucose Type 1 diabetes Type 2 diabetes GDM Jovanovic L, Peterson CM. Am J Med. 1983;75:607-612 Glucose (mg/dL)
  • 142. Postpartum Considerations Lactation and Nutrition • Breastfeeding is recommended – Decreased risk of type 1 diabetes and infection in infant, Decrease incidence of type 2 by ½. – 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 normoglycemia cannot be maintained with MNT • Women with previous GDM have – 40% to 60% risk of developing type 2 diabetes in 5 to 15 years – 66% risk of GDM in future pregnancies
  • 143. Breastfeeding and DM meds • Both metformin and glyburide/glipizide are found at low concentrations (or not at all) in breast milk – Hale et al, Diabetologia 2002 – Feig et al, Diabetes Care 2005 – Can be considered however, more long-term studies needed
  • 144. Contraception Type % Effectiveness Acceptability Notes Oral contraception 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 Intrauterine 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
  • 145. Birth Weight and Risk of Future Type 2 Diabetes 0 5 10 15 20 25 2500 g 3500 g 4500 g Birth weight Percent 1500 g Jovanovic L. Diabetes Care. 2000;23:1219-1220 McCance DR et al. BMJ. 1994;308:942-945 3 lb, 5 oz 5 lb, 8 oz 7 lb, 11 oz 9 lb, 14 oz
  • 146. • Gestational diabetes 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 Conclusion
  • 147. KATHMANDU DECLARATION Primary prevention ‘‘Life Circle’’ approach
  • 148. Primary prevention strategies • Preconception – Educate that pregnancy can be a risk factor – Infections/inflammation – Screen for diabetes and its risk factors in the potential mother
  • 149. • Pregnancy – Fetal programming • Maternal nutrition • Prenatal psychosocial stress • Screening during pregnancy • Postnatal follow-up
  • 150. – Infancy and childhood • Nutrition of the infant • Monitor growth and well-being • Legislation to promote good dietary environment • Physical activity • Risk assessment and lifestyle modification • Initiate nutrition, physical activity and stress reduction programmes in educational institutions and the community
  • 151. – Adult life • Screening for high risk individuals • Proper nutrition • Encourage physical activity • Stress in adult life • Promote employer and employee education • Increased awareness and education throughout the ‘‘Life Circle’’ • Secondary prevention strategies – Multi-factorial/multi-disciplinary/multi-sectoral approach to care – Access to quality essential medicines to all