Gestational Diabetes Mellitus: A Current Approach

Transcription

1 Gestational Diabetes Mellitus: A Current Approach jkendric@utmck.edu Jo s Office GDM-carbohydrate intolerance of any degree with onset or diagnosis during pregnancy (ADA, 2012) GDM A 1 -diet controlled GDM A 2 -insulin requiring 1

2 KendrickJ_Gestational Diabetes: A Current GDM comprises 90% of all DM in pregnancy Reported rates of GDM 5-14% of all pregnancies-true incidence unknown due to lack of uniform diagnostic criteria Five to 10% of women with GDM have undiagnosed type 2 DM Women over the age of 20 comprise over half of individuals with diabetes type 2 diabetes and only 25% know it New diagnostic criteria for GDM will increase incidence to 18% of all pregnancies Increasing prevalence due to delayed childbearing and obesity Overweight increases risk factor (RF) by 2.1; obese increases RF 3.6; severely obese increases RF 8.6 NIDDK, NATIONAL DIABETES STATISTICS, 2011 Obesity 26% Diabetes 9% 2

3 Weekly food expenditure: $ Food expenditure for one week: Egyptian Pounds or $

4 PORTABLE PHONES REMOTE CONTROLS 4

5 How Food is Digested 1. Food enters stomach 4. Pancreas releases insulin 5. Insulin unlocks receptors 6. Glucose enters cell 2. Food is converted into glucose 3. Glucose enters bloodstream Anabolic Phase enhanced insulin secretion due to estrogen, progesterone mediated beta cell hyperplasia-hyperinsulinemia increased insulin sensitivity exogenous insulin needs decreased lipogenesis and fat deposition 5

6 Catabolic Phase diabetogenic state decreased insulin sensitivity due to antiinsulin placental hormones Accelerated starvation-fat breakdown/lipolysis decreased acid buffering capacity increased risk for DKA dramatically increased insulin needs First prenatal visit all or at risk Fasting plasma glucose (FPG)->126 mg./ dl. Hgb Aic-6.5% Random Plasma Glucose (RPG)->200 mg./ dl.* If FPG is , considered early GDM If all of the above normal then administer 75 gram OGTT at weeks International Association of Diabetes and Pregnancy Study Groups (IADPSG, 2010). Diabetes Care, 33,#3, March MEASURE OF GLYCEMIA THRESHOLD Fasting Plasma Glucose > 126 mg./dl (FPG) A1c > 6.5% Random plasma glucose > 200 mg./dl confirmed* (RPG) *Random plasma glucose must be confirmed by FPG or A1c Accepted by ADA, 2010, Rejected by ACOG,

7 Timing Criteria mg./dl mmol/l Fasting plasma glucose hr plasma glucose 2 hr plasma glucose *One abnormal values constitutes GDM Accepted by ADA, 2010, Rejected by ACOG, 2011 Low risk does not require screening Age < 25 years Pre-pregnancy weight normal (BMI of 25 or less) No known diabetes in first degree relatives Not a member of high risk racial-ethnic group Hispanic African American Native American Asian No history of abnormal glucose tolerance No history of poor obstetric outcome American Diabetes Association; 2008 Requires testing between weeks Abnormal pre-pregnancy weight High risk racial ethnic heritage Family history of type 2 diabetes in first degree relative History of abnormal glucose tolerance test History of poor obstetric outcome History of fetal macrosomia (>4000 grams) American Diabetes Association;

8 Requires testing as soon as pregnancy confirmed: Severe obesity Prior history of GDM or delivery of a large-for gestational age infant Presence of glycosuria Diagnosis of polycystic ovarian syndrome Strong family history of type 2 diabetes American Diabetes Association; gram 1 hour oral glucose challenge test (GCT) Positive at 130 mg./dl ( non fasting)*** Requires step #2---3 hour OGTT Requires 25% of women to have OGTT Positive at 140 mg./dl (fasting) *** Requires 15% to have OGTT but will miss 10% Diagnostic at 200 mg./dl. ***Berkus, Stern, Mitchell et al. Does fasting interval affect the glucose challenge test? Am J Obstet Gynecol 1990;163: Diagnostic 3 hour oral glucose tolerance test 100 gm(ogtt) for high risk population or 75 gram OGTT Plasma fasting prior to ingestion Diagnostic for GDM at 120 mg./dl. Testing should be performed after an overnight fast with no smoking or activity during test. Diet prior to fast should be unrestricted (150 gms. CHO) for 3 days 8

9 Organization Test type Diagnostic threshold ACOG (2011) 100 gm 3 h. OGTT 75 gm National Diabetes Data Group (NDDG) F: >105 1 hr >195, 2 hr.>165 3 hr>145 Carpenter & Coustan F.>95, 1 hr> 180, 2 hr.>155, 3 hr.>140 F> 95, 1 hr>180, 2 hr.>155 WHO (2010): ADA gm OGTT F: >92, 1 hr>180, 2hr >153 Mullholland, Njorge, Mersereau & Williams, Comparison of guidelines available in the US for diagnosis and management of diabetes Before, during and after pregnancy. Journal of Women s Health, 16, DIABETES DIABETES DIABETES DIABETES Women with risk factors with normal 3 h OGTT may benefit from repeat testing at 32 weeks 1 Macrosomia associated with one abnormal value 2 consider nutrition intervention and repeat OGTT 4 weeks later 1. Neiger, Coustan.(1991) The role of repeat glucose tolerance tests in the diagnosis of GDM. Am J Obstet Gynecol,165: Lindsay, MK., Graves, Klein. (1989). The relationship of one abnormal glucose tolerance test value and pregnancy complications. Obstet Gynecol, 73;

10 Total of 25,505 women in 15 centers in nine countries Took 9 years and 20 million dollars 75 gm OGTT between weeks Blinded to women with FPG < 105 and 1 or 2 hour PG <200 mg./dl. The Analysis HAPO Study based cooperative on Research assigned Group (2008). glucose Hyperglycemia category and adversepregnancy outcome. NEJM 358 (19); Category Fasting Glucose 1 hr. Glucose 2 hr. Glucose 1 <75 <105 < or more 212 or more 178 or more Directly proportional change in outcomes to maternal glucose Adjusted for confounders of maternal BMI, previous macrosomia and previous GDM Outcome measures Birth weight Umbilical cord c-peptide (chosen due to stability in frozen sample) Incidence of cesarean delivery Incidence of neonatal hypoglycemia 10

11 Secondary outcome measures with positive associations(related to 1 and 2 hr. glucose but not fasting) Preeclampsia Shoulder dystocia or birth injury Premature delivery Intensive neonatal care hyperbilirubinemia The HAPO Study Cooperative Research Group. N Engl J Med 2008;358: Evaluated the HAPO results and published their recommendations for screening and diagnosis of hyperglycemia in pregnancy in Diabetes Care 2010;33:

12 International consensus recommendation for the screening and diagnosis of gestational diabetes 75 gram OGTT, one abnormal value Thresholds: FBS: 92 (8.3%) OR 1 hr.: 180 (5.7%) OR 2 hr: 153 (2.1%) Total: 17.8% Odds ratio of 1.75 FOR PRIMARY OUTCOMES Prevalence of GDM will be increased to 17.8 % which more closely reflects the incidence of T2dm/pre dm Cost/benefit analysis not obtained Requires the availability of dietitians, diabetes educators and staff for increased surveillance of these pregnancies Additional costs associated with therapy Number of inductions will be increased and risk for CS Requires fasting and morning appt. Overt DM can be detected and treated and vascular disease assessment obtained during pregnancy, allows postpartum referral, negating need for further testing Will allow a global data base and true epidemiology and prevalence determined Treating lower glycemic thresholds may reduce risks for metabolic syndrome/t2dm later Treating lower thresholds should reduce the risk of adverse outcomes 12

13 Japan Parts of India Germany (with modifications) China (with modifications) Italy Brazil (with modifications) The American Diabetes Association WHO has reviewed HAPO data and other data and will publish revised guidelines soon. NIH will hold a consensus conference October 29-31, 2012 and will make independent recommendations that may or may not be the same as IADPSG. (Boyd Metzger, 2012) Pre eclampsia/eclampsia HTN and worsening of HTN Urinary tract infections Polyhydramnios Preterm labor/birth Spontaneous abortion Cesarean section Operative delivery Managing Preexisting Diabetes and Pregnancy, 2008 Fraser RA, 2010; Ogata ES, 2008;Hawson JM, 2010;Girling J, 2010 complication incidence cause Hypoglycemia 10-25% Excessive neonatal insulin secretion Hypocalcemia Hypomagnesemia Polycythemia Cardiomyopathy Hyperbilirubinemia Respiratory Distress Syndrome (RDS) Stillbirth 50% 33% 5-6% <1% 20-40% 2-6% 2.5-4% Transient hypoparathyroidism Often secondary to hypocalcemia Intrauterine hypoxia Anabolic effect of hyperinsulinemia Increased hemolysis, ineffective erythropoiesis Decreased surfactant production with hyperinsulinemia Polyhydramnios, chronic fetal hypoxia or acidemia 13

14 Cesarean birth Excessive blood loss Infection Wound breakdown Macrosomia HTN GDM Fetal death Birth defects-ntd Longer hospital stays Miscarriage Inability to monitor fetus Difficult epidural or spinal anesthesia Higher NICU admissions Increased deep veinthrombosis n=323, 1 hr. <130 PP, predicted 28% macrosomia (Institute control prior to 32 weeks) (DIEP, J Obstet Gynecol, 164:1991) 1 hr. PP decreases risk of macrosomia from 42% preprandial to 12% (DeVenciana et al. N Engl J Med. 333:1995) 1 hr PP BG< 120 mg./dl eliminates macrosomia (Combs et al. Diabetes Care, 15; 1992) 1 hr. PP BG < 120 decreases risk of neonatal hypocalcemia (Demarini et al. Obstet Gynecol. 823; 1994) Mean PP BG of <105 significantly correlated to abd. circumference (Paretti et al. Diabetes Care 24;2001) Significant reduction in LGA and emergent CS in 1 hr. PP testing and pt. preference (Moses et al. Aust NZ J Obstet. Gynecol, 39; 1999) 14

15 Organization Capillary Blood Glucose (mg./dl) ADA, 2010 Fasting Peak Postprandial 1 h Mean Daily BG <110 A1c <6.0% AACE (2007) Fasting Peak Postprandial 1 hr <120 Initiate Insulin >90 >120 post meals A1c <6.0% ACOG, 2005 Fasting <95 Premeal <100 Postprandial 1 hr. <140 Postprandial 2 hr. <120 Mean Daily BG 100 A1c <6.0% 15

16 Individualized meal plan based on BMI, height, weight and gestational age Consider cultural, ethnic, religious influences, schedule and finances Carbohydrate content divided between meals and snacks 175 grams CHO, 28 gms fiber, 1.1 gm/kg/day protein (Reader, DM, 2008) Non-nutritive sweeteners approved by FDA in pregnancy Saccharin, aspartame (except in PKU), acesulfame K, sucralose neotame-not always recommended Monitor weight gain and loss and tolerance of therapy Prenatal vitamin with DHA Calcium 1500 mg/day, folic acid 600mcg/day (dietary or supplements) Avoid alcohol/smoking Limit caffeine to 300mg/d, artificial sweeteners 1-2 portions/day Avoid fish potentially high in mercury Increase calories after 1 st trimester by300kcal/ day Reader, Managing Preexisting Diabetes and Pregnancy, 2008 BMI IOM, 2009 Kiel et al, 2007 Cedergren, 2007 < lbs 9-22 lbs lbs 5 to 22 lbs > lbs <20 lbs > lbs No more than 13 lbs lbs > lbs > lbs wt. loss 16

17 May decrease maternal glucose levels decreasing need for insulin or amount of insulin required Planned physical activity of 30 minutes daily unless contraindicated, well hydrated with HR less than 150 bpm Arm exercise in GDM while seated for 10 minutes postmeal reduces BG May decrease stress and anxiety Summary and Recommendations of Fifth International Workshop Conference on GDM (2008) Pregnancy Considerations Risks of moderate-intensity activity done by healthy pregnant women very low Risks for low birth weight, preterm birth or early pregnancy loss not increased May reduce risk of pregnancy complications; preeclampsia and gestational diabetes Key Guidelines 150 minutes (2 hrs./30 minutes) of moderate intensity aerobic activity per week for women who are NOT already highly active Pregnant women who habitually engage in vigorousintensity aerobic activity may continue Avoid doing exercise lying on back after the first trimester Avoid activities that increase the risk of falling or abdominal trauma Contact or collision sports Horseback riding, downhill skiing, soccer, basketball 17

18 CONTRAINDICATIONS Significant heart or lung dz. Incompetent cervix Persistent bleeding Preterm labor (PTL) Multiple gestation-ptl Ruptured membranes Pregnancy induced hypertension WARNINGS TO DISCONTINUE Vaginal bleeding Dyspnea Headache Chest pain Decreased fetal movement Amniotic fluid leaking Muscle weakness Preterm labor Calf pain or swelling Dawn P. Coe 1, Jo M. Kendrick 2, Bobby Howard 2, David R. Bassett Jr. 1, FACSM, Dixie L. Thompson 1, FACSM, Scott A. Conger 1, and Jennifer D. White 1 Day Monday (1) Tuesday (2) Wednesday (3) Thursday (4) Friday (5) Events Ini3al visit, inser3on of the Con3nuous Glucose Monitoring System (CGMS), and pedometer placement. Fixed carbohydrate meal for lunch, 30 minutes res3ng, and either 30 minutes of walking on the treadmill or 30 minutes of TV. No visit. Fixed carbohydrate meal for lunch, 30 minutes res3ng, and either 30 minutes of walking on the treadmill or 30 minutes of TV. Final visit and removal of the CGMS Results Figure 1. Postprandial glucose levels following walking and sedentary condi9ons Glucose Levels (mg/dl) Pre-Treatment * Post-Treatment ** 2 Hours 3 Hours 4 Hours 5 Hours Postprandial Glucose Levels 6 Hours Walk Sedentary *p<0.001 **p<

19 Pharmacologic Intervention Insulin only FDA approved treatment for diabetes in pregnancy Glyburide-second generation sulfonylurea Insulin secretagogue Onset of action 4 hrs lasting 10 hrs. Low placental transfer Metformin-biguanide Decreases hepatic conversion of glycogen to glucose Improves peripheral insulin sensitivity Crosses placenta freely 19

20 Lispro/Aspart, Humulin/Novolin N, Detemir category B Glargine category C Algorithm based on weight Preconception 0.6U/kg/day First Trimester (6w) 0.7U/kg/day Second Trimester(16w) 0.8U/kg/day Third Trimester(26w) 0.9U/kg/day >150%ideal 1.5 to 2U/kg Basal (50%) and bolus insulin (50%), evaluate BG Adapted from Jovanovic and Peterson,1982. Evaluate blood glucose every 1 to 2 weeks based on glycemic control Serial ultrasound to assess growth after weeks Fetal kick counts at 28 weeks Begin weekly to twice weekly fetal testing by electronic fetal monitor or ultrasound based on any co-morbidities and level of glycemic control Deliver at 39 to 40 weeks 20

21 Macrosomia (>90percentile) > 4000 gms. (8# 13 oz) incidence % with good control, 25-42% without normoglycemia (Langer,2004) Organomegaly-heart, liver Fetal echo r/o hypertrophy with impaired cardiac function which is associated with fetal death (Leslie 82: Sardesai 01) excessive fat deposition (shoulders & trunk) birth trauma-shoulder dystocia, fractured clavicles, brachial plexus injury, asphyxia, and other injuries intrauterine growth restriction (IUGR) < 10th percentile carries significant risk for neonatal death (Boulet 06) incidence 20 % associated with vasculopathy, HTN, placental insufficiency, decreased renal function, smoking LONG TERM RISKS Obesity Insulin resistance Glucose intolerance T2dm GDM (females) HTN Other types of cardiovascular disease RISK REDUCTION Parents should be educated regarding long term risks Encourage breast feeding Encourage healthy diets and active lifestyle Providers should monitor growth and development of children 21

22 Conway & Catalano, 2008 Consider week delivery-well controlled, no comorbidities earlier with amnio for FLM with worsening vascular disease, poor glycemic control, macrosomia Continuous fetal heart rate monitoring Maintain normoglycemia ( mg./dl) to minimize risk of neonatal hypoglycemia Maternal bedside BG monitoring every 1-2 hrs Continuous infusion of insulin/and/or glucose as indicated May use basal rate on insulin pump and bolus as indicated Insulin resistance dramatically improves immediately after birth GDM resolves Insulin/oral medications require dosage decrease of 50% in women with prepregnancy diabetes Breast feeding Requires 500 additional calories Not all oral medications are safe Decreases insulin requirements in type 1 and 2 diabetes Decreases risk of development of type 2 diabetes and obesity in offspring (Dabelea, 2007; Schaefer-Graf et al, 2006) Decreases risk of transmission of type 1 diabetes (Virtanen & Knip, 2003) 22

23 EDUCATION Risk of GDM subsequent pregnancy-30-84% (Kim, Berger & Chamany, 2007) Lifetime risk of overt diabetes 50-60% (AACE, 2007; Kjos, 2007) Lifestyle modifications and metformin decreases the risk of development of type 2 diabetes (Ratner et al, Diabetes Prevention Research Group, 2008) Test every 1 to 3 years and prior to subsequent pregnancy (ADA, 2012) Preconceptual counseling 75 gram 2 hr. glucose tolerance test 36% obtain f/u testing 32% of physicians order 75 gm Providing written requisition increases testing frequency (Kim, 2007) Normoglycemia IFG and IGT Diabetes Mellitus FPG <100 FPG between FPG> 126 mg./dl mg./dl 2 hr plasma glucose <140 2 hr. plasma glucose mg./dl 2 hr. plasma glucose > 200 mg./dl Symptoms of diabetes mellitus and casual plasma glucose >200 mg./ dl Diagnosis must be confirmed on a subsequent day of any of the three methods in the absence of unequivocal hyperglycemia. 23