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Www.drsarma.in1. 2 Glucose Challenge Test (GCT) An excellent screening test is to obtain plasma glucose level one hour after a 50 g glucose load administered.

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Presentation on theme: "Www.drsarma.in1. 2 Glucose Challenge Test (GCT) An excellent screening test is to obtain plasma glucose level one hour after a 50 g glucose load administered."— Presentation transcript:

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2 2 Glucose Challenge Test (GCT) An excellent screening test is to obtain plasma glucose level one hour after a 50 g glucose load administered at any time of the day without regard to the time since the last meal. It is a well validated and widely applied screening procedure for women between weeks of gestation. Cut-off value > 140 mg/dl identifies 80% women with GDM Cut-off value > 130 mg/dl identifies 90% women with GDM GCT is elevated, do a diagnostic oral glucose tolerance test

3 3www.drsarma.in Timing of measurement National Diabetes Data Group (1979) Carpenter and Coustan (CC) 1982 Fasting105 mg/dl95 mg/dl 1 hour190 mg/dl180 mg/dl 2 hour165 mg/dl155 mg/dl 3 hour145 mg/dl140 mg/dl Diabetes 1979;28:1039–1057; Am J OBG. 1982;144: or more values must be abnormal; for at least 3 days prior to the test, the patient should have an unrestricted diet and unlimited physical activity. The patient should fast for 8 hours before the test. The CC criteria detects 54% more women with GDM than NDDG criteria

4 4www.drsarma.in Test sample timing Plasma Glucose value Fasting (mg%)95 1 hour (mg%)180 2 hour (mg%)155 3 hour (mg%)140

5 Tight glycemic control can reduce fetal risk. But, stringent glycemic control puts the mother at increased risk of hypoglycemic events and the fetus at risk of being small-for-gestational age. American Diabetes Association (ADA) Recommendations: Fasting whole blood glucose<95 mg/dl 1 hr postprandial blood glucose <140 mg/dl 2 hr postprandial blood glucose <120 mg/dl Hb A1C (for GDM)< 6.0 % These are venous plasma targets, not glucometer targets

6 6www.drsarma.in HbA1C – not ideal for screening of GDM May used for screening of T2DM Patients with excessive fetal growth - Insulin Those who don’t achieve targets in 1w- Insulin Target values –Hb A1c < 6%; Pre pregnancy Hb A1c < 7% –Fasting – < 95 mg% –Post prandial 1 hour – < 120 mg % –Post prandial 2 hours – < 140 mg% –Urine ketones should be negative Diabetes Care 21(2):B161–B167, 1998, Diabetes Care 2010; 33: 676–682

7 7www.drsarma.in Uterin e After Birth Maternal DM Placenta AA, Fat CHO At Birth Macrosomi a Hypoglycemi a Fetus  Insulin Obesit y Metabolic Syndrome CVD IGT/DM

8 8www.drsarma.in Optimal Nutrition + Optimal Glycemic Control Results in optimal birth weight of 3–3.5 kg. HTN, IGT Type 2 DM Barker’s Hypothesis Low birth weight Pederson’s hypothesis Macrosomia

9 9www.drsarma.in First Half of Pregnancy (Anabolic) –Pancreatic beta-cell hyperplasia  hyper insulinemia –Increased uptake and storage of glucose Second Half of Pregnancy (Catabolic) –Placental hormones block glucose receptors and cause insulin resistance Increased lipolysis Increased gluconeogenesis Decreased glycogenesis –Increased glucose and amino acids for the fetus

10 10www.drsarma.in Pregnancy is Diabetogenic condition A Wonderful Metabolic Stress Test Placental Diabetogenic Hormones –Progesterone, Cortisol, GH –Human Placental Lactogen (HPL), Prolactin Insulin Resistance (IR), ↑  cell stimulation Reduced Insulin Sensitivity up to 80% Impaired 1 st phase insulin, Hyperinsulinemia Islet cell auto antibodies (2 to 25% cases) Glucokinase mutation in 5% of cases

11 11www.drsarma.in The hormones of pregnancy cause IR They also cause direct hyperglycemia But, the basic defect is The maternal pancreatic  cells are unable to compensate for this increased demand Plasma Glucose in pregnancy hangs on a delicate balance If the Mean Plasma Glucose (MPG) is –Less than 87 mg% - IUGR of fetus –More than 104 mg% - LGA of fetus It is important to screen for hypothyroidism

12 12www.drsarma.in Does GDM pose serious risks to offspring? Does treatment reduce those risks? Does treatment reduce other risks associated with GDM (obesity/diabetes in offspring)? Does reducing hyperglycemia reduce risks? (macrosomia & cesarean delivery)

13 13www.drsarma.in 1 Poor Pregnancy outcomes and mortality High maternal & perinatal morbidity 2 High risk of future onset of diabetes in mothers A good primary prevention opportunity 3 Metabolic problems in the offspring Including high incidence of diabetes

14 14www.drsarma.in Mean glucose is >150 – PN Mortality is 24% Mean glucose is PN Mortality is 15% Mean glucose is <100 – PN Mortality is 4%

15 15www.drsarma.in Maternal HbA1c levels < 7.2Nil % % > % Critical periods weeks post conception Need preconception metabolic care

16 16www.drsarma.in ComplicationMean blood glucose Spontaneous abortion160 mg% Congenital anomalies140 mg% Still births140 mg& Lung maturation140 mg% Metabolic complication110 mg% Macrosomia or LGA110 mg%

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20 20www.drsarma.in Insulin discovery by Banting and Best Commercial insulin with impurities Higher quality Bovine and Porcine Insulin Synthetic Human Insulin Synthetic human insulin approved Synthetic recombinant human insulin Sequencing the human insulin receptor Lispro insulin (Lilly) analogue Glargine insulin (Sanofi Aventis) analogue Glulisine (Sanofi Aventis) analogue Detemir insulin (Novo Nordisk) analogue

21 21www.drsarma.in Mimic physiological control No adverse effect upon maternal and fetal outcome. No interfere with antenatal, perinatal & post natal care IgG bound insulin can cross placenta. So insulin should not induce antibody generation Insulin Analogues fulfills all the criteria Mimic physiological insulin secretion Does not cross placenta No mitogenic potential

22 22www.drsarma.in Analogue Change in amino acid sequenceType Lispro28-29 Proline and Lysine are interchangedRapid AspartProline at 28 replaced by Aspartic acidRapid Glulisine3 Lysine by Asparagine; 29 Lysine by GlutamineRapid GlargineA21 Asparagine by Glycine; 2 Arginine to C terminal BLong DetemirB 30 Threonine by Myristic acid a C-14 Fatty acidLong

23 23www.drsarma.in AnalogueBrand NameManufacturer FDA LisproHUMALOGEli LillyB AspartNOVOLOGNovo NordiskB GlulisineAPIDRASanofi AventisC GlargineLANTUS(R)Sanofi AventisC DetemirLEVEMIRNovo NordiskB

24 24www.drsarma.in Batch to Batch consistency No allergy, antibody formation No immune mediated lipoatrophy Glucose control is similar in endogenous insulin production Pre prandial hypoglycemia and postprandial hyperglycemia are well controlled. Mealtime flexibility is possible with analogues.

25 25www.drsarma.in Maternal More physiological profile Better glycemic control Minimum hypoglycemia risk Greater meal time flexibility Fetal Low fetal hypoglycemia risk Less Macrosomia, defects Fewer C-sections Better pregnancy outcomes

26 26www.drsarma.in Brunzell JD et al. J Clin Endocrio Metab. 1976; 42:

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28 28www.drsarma.in Barnett AH, Owens DR, Lancet 1977; 349:97-99 and 1997,101:60-70

29 29www.drsarma.in Basal Basal Plus Basal Bolus Spilt Mix AM+PM CSII + CGMS

30 30www.drsarma.in Two parameters – Weight and Gestational age The level of blood sugar is not the criterion Insulin requirements increase rapidly, especially from 28 to 32 weeks of gestation –1 st trimester: U/kg/day –2 nd trimester: U/kg/day –3 rd trimester: U/kg/day Increase every 3 days by 2 units based on BGM

31 31www.drsarma.in Titrate insulin based on SMBG values: Fasting Pre-meal <95 2 hour post-meal <120 Bedtime <120

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34 34www.drsarma.in NICE Clinical Guideline 63 March 2008

35 35www.drsarma.in Blood GlucoseIV Fluid with or without Insulin mg%5% DNS – 100 ml/hr mg%NS or RL – 100 ml/hr mg%NS or RL – 100 ml/hr + 4 U R Insulin mg%NS or RL – 100 ml/hr + 6 U R Insulin > 180 mg%NS or RL – 100 ml/hr + 8 U R Insulin In GDM Insulin requirement precipitously drops after placental expulsion

36 36www.drsarma.in Total 24 hour Insulin requirement in 60 kg 1 st Trimester 60 x 0.7 = 42 units – 2/3 pre BF = 28 U, 1/3 = 14 U evening Of the 28U – 2/3 NPH and 1/3 Regular = (19 + 9) in one inj. Of the 14U – ½ Regular pre supper (7U) and ½ NPH at bed

37 37www.drsarma.in Patient Resistance: (Psychological Insulin Resistance) –Compliance issues, Needle phobia –Fear of scarring, Fear of wrong dosage –Financial, Difficulties in administration Physician Resistance (Clinician Inertia) –Lack of resources and knowledge of Insulins –Lack of time to plan/follow/educate intensive regimen Perceived and real adverse effects –Weight gain; Hypoglycemia –Optimal control requires multiple injections

38 38www.drsarma.in Crowther et al – Multicenter – 1000 pts. Langer et all – 1100 GDM, 1100 Normal HAPO: 28,000 women (Hyperglycemia And Adverse Pregnancy Outcome) ACHOIS (Australian Carbohydrate Intolerance Study) MFMU Maternal and Fetal Medicine Unit (NICHD) GDM Trial Int J Gynecology & Obstetrics. 2002,78, (1);69-77

39 39www.drsarma.in Langer et al - NEJM 2000: , Oct 19

40 40www.drsarma.in OAD in Pregnancy: The Other Alternative, O. Langer,

41 41www.drsarma.in OAD in Pregnancy: The Other Alternative, O. Langer,

42 42www.drsarma.in Current Diabetes Reviews, 2009, 5, Glibenclamide – Class B, may be other SUs Metformin – Class B ( No statins, No ACEi, ARB) TZD – Not to be used, AGI – Class B GLP-1, DPP IV Inhibitors – More studies needed

43 43www.drsarma.in New generation of oral hypoglycemic agents glyburide does not cross the placenta and may be used to replace insulin between wks. Metformin can be used in P.C.O. patients during the whole pregnancy. It showed that it reduces miscarriages and the incidence of GDM TZDs not studied in pregnancy – not a choice AGIs – weak drugs – GI side effects - local action GLP-1 and DPP IV Inhibitors not studied yet

44 44www.drsarma.in Expert Rev. Endocrinol. Metab. 7(2), 165–167 (2012) Selective v/s Universal screening Single 50g GCT v/s 100g OGTT OADs – Poor Women’s Insulin

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46 46www.drsarma.in Abstract Diabetes in pregnancy is associated with risks to the woman and to the developing fetus. Miscarriage, pre-eclampsia, preterm labour and congenital malformations in fetus are more common in women with pre-existing diabetes. Insulin requirement increases with each trimester of pregnancy in diabetic females. Treatment of gestational diabetes consists of medical nutrition therapy but insulin treatment forms the mainstay of the therapy. Monitoring glycemic control is essential in treatment of gestational diabetes. HbA1c level is helpful to differentiate between a pre-GDM and GDM. Majority of pregnant women with diabetes fail to achieve optimum glycemic control, mostly the postprandial plasma glucose with conventional insulin. In them, the best option is to administer ultra- short-acting analogs, insulin Lispro or insulin Aspart. These analogs improve the postprandial glucose control during pregnancy in both type 1 and type 2 diabetes and are considered safe and effective. Supplement to JAPI April 2011 VOL. 59

47 47www.drsarma.in NICE Clinical Guideline 63 March 2008

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49 49www.drsarma.in Blood glucose levels monitored continuously Pre specified insulin dose is s/c delivered by pump This minimized timing and dosing errors. Blood glucose is assessed periodically Insulin dose is calculated CGMS is integrated with a delivery device – blue tooth Hence round the clock blood glucose is controlled.

50 50www.drsarma.in When used within ADI Aspartame (NutraSweet) –does not cross placenta; –No adverse effects Sucralose (Equal) – acceptable Acesulfame K (Sunnet) – acceptable Saccharin (Nectra Sweet, Sweet Twin) – Crosses placenta; not acceptable Cyclamate (Sucril) – not acceptable

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