Gestational Diabetes: Long Term Metabolic Consequences Gladys (Sandy) Ramos, MD Associate Clinical Professor Maternal Fetal Medicine Outline Population rates of obesity and T2DM Obesity and metabolic syndrome What s new in diagnosis of type 2 DM? Fetal and neonatal effects of GDM Maternal effects of GDM Interventions to prevent T2DM Age-Adjusted Prevalence of Obesity and Diagnosed Diabetes Among U.S. Adults Aged 18 Years or older Obesity (BMI 30 kg/m 2 ) 1994 2000 2010 Diabetes No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0% 1994 2000 2010 No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0% CDC s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics 1
>1/3 of women in the US are Obese 64% are overweight or Obese USA: Diabetes & Prediabetes - Diagnosed And Undiagnosed --10.7% Diabetes + 19% Prediabetes = approximately 29% of adult US population 2
Adipose-immune interactions during obesity. Dixit V D J Leukoc Biol 2008;84:882-892 Metabolic Syndrome Obesity Insulin Resistance/Diabetes Dyslipidemia/Heart Disease Hypertension 2-3 Fold increased risk of T2DM and premature cardiovascular disease Prevalence of Metabolic Syndrome in U.S. Adults Ford et al, JAMA. 2002 3
Diagnosis of T2DM and prediabetes 2010: Criteria for diagnosis of diabetes 1. A1C 6.5%. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* OR 2. FPG 126 mg/dl. Fasting is defined as no caloric intake for at least 8 h.* OR 3. 2-h plasma glucose 200 mg/dl during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* OR 4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose 200 mg/dl. *In the absence of unequivocal hyperglycemia, criteria 1 3 should be confirmed by repeat testing. DIABETES CARE, VOLUME 33, JANUARY 2010 Dx and Classification of DM Prediabetes 2010 Glucose Categories of increased risk for Diabetes Prediabetes: A1C 5.7 6.4% IFG: FPG 100 mg/dl to 125 mg/dl IGT: 2-h PG ;75-g OGTT 140 mg/dl to 199 mg/dl *For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher ends of the range DIABETES CARE, VOLUME 33, JANUARY 2010 Dx and Classification of DM 4
Diagnostic Criteria in Pregnancy Prior to 24 weeks Same Criteria Fasting > 126 mg/dl A1C >6.5% Random plasma glucose of >200mg/dL+ confirmation Neonatal Effects of GDM Pederson Hypothesis FETUS FETAL HYPERGLYCEMIA PLACENTA MOTHER GLUCOSE FETAL HYPERINSULINEMIA (cord c-peptide) INSULIN MACROSOMIA 5
Adult Obesity After Prenatal Diabetes Exposure BMI was 2.6 kg/m 2 higher Dabelea et al, Diabetes, 2000 Childhood Metabolic Syndrome: Effect of Exposure to Maternal GDM Charlotte M. Boney, et al. Pediatrics 2005 Long Term Effects Matorell, et al J. Nutr. 2001 6
Are Our Children Becoming Obese HAPO Trial Observational Trial Given a 75-gram 2-hour oral glucose tolerance test (OGTT) at about 28 weeks of gestation Exclusion criteria Fasting>105 2 hour >200 Routine prenatal care HAPO Trial Primary Outcomes BW>90 th %ile Neonatal hypoglycemia Neonatal hyperinsulinemia (c peptide>90 th %ile) Primary cesarean delivery Secondary Outcomes Neonatal fat mass Shoulder dystocia Preterm delivery Pre-eclampsia NICU admission 7
Results of HAPO Fasting Plasma Glucose and Outcomes 1-Hour Plasma Glucose and Outcomes 8
2-Hour Plasma Glucose and Outcomes Can Treatment of GDM Reduce Fetal Obesity? Two RCTs 9
Treatment of GDM Reduces Adverse Outcome OUTCOME ROUTINE CARE (N = 510) INTERVENTION (N = 490) P Birth Weight 3482 + 660 3335 + 551 <.001 LGA 22% 13% <.001 Macrosomia 21% 10% <.001 Preeclampsia 18% 12% 0.02 20% of intervention group required insulin SGA 7% 7% ns Crowther CA, et al. NEJM, 2005 12% of patients in treatment group required pharmacotherapy Landon, et al. NEJM 2009 10
Long Term Effects X Breastfeeding Long Term Maternal Effects Risk Factors for GDM Incidence 3-5% Ethnic Groups African Americans Asians Latinas American Indian Others AMA Obesity Tobacco Family History 11
Glucose metabolism in GDM GDM and Type 2 DM Type 2 DM is characterized by: Glucose intolerance Peripheral insulin resistance Impaired regulation of hepatic glucose production Declining Beta-cell function Longitudinal study GDM vs. Controls Followed for 11yrs Vohr and Boney, J Matern Fetal neonatal Med, 2008 12
Vohr and Boney, J Matern Fetal neonatal Med, 2008 Type 2 DM- 12.7% (GDM) vs. 4.1% (controls Metabolic Syndrome 27.2% (GDM) vs. 8.2% (controls) Vohr and Boney, J Matern Fetal neonatal Med, 2008 Forest plot of overall risk of MS after GDM Xu Y, Shen S, Sun L, Yang H, et al. (2014) Metabolic Syndrome Risk after Gestational Diabetes: A Systematic Review and Meta- Analysis. PLoS ONE 9(1): e87863. doi:10.1371/journal.pone.0087863 http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087863 13
Interval of time Kim, Newton, Knopp, Diabetes Care, 2002 Long Term Effects X Breastfeeding How to modify these risks? 14
Diagnostic Criteria Prediabetes: A1C 5.7 6.4% IFG: FPG 100 mg/dl to 125 mg/dl IGT: 2-h PG ;75-g OGTT 140 mg/dl to 199 mg/dl T2DM: A1C >6.5% 2-h PG ;75-g OGTT >200mg/dl Fasting >126mg/dl DIABETES CARE, VOLUME 33, JANUARY 2010 Dx and Classification of DM Postpartum Screening 6 weeks post partum, 75gram 2 hour GTT Breastfeeding- Short term Pregnancy characterized Insulin resistance Elevation in fasting triglycerides Breastfeeding characterized Improved insulin sensitivity Decrease in lipids Fat store mobilization Weight loss Lower rates of metabolic syndrome --Particularly GDM 15
Breastfeeding- Long Term Gunderson et al. Diabetes 2010 Breastfeeding- Childhood effect Schaefer-Graf et al. Diabetes Care 2006 ADA recommendations IGT, IFG, Prediabetes Weight loss of 7% Increased physical activity- moderate exercise 150 min/weeks Counseling Metformin- BMI>35kg/m, Age<60yrs, prior GDM Annual screening for type 2 DM Screening and treatment of modifiable risk factors for CVD http://www.cdc.gov/diabetes/prevention/about.htm 16
Lifestyle modification Trial Duration of Trial (yrs) T2DM Risk Reduction Da Qing Trial, Lancet 20 43% 2008 Finnish Diabetes Prevention Study Group, Lancet 2006 7 43% Diabetes Prevention Program Research Group, Lancet 2009* *US trial 10 34% Metformin Ratner et al, JCEM 2008 Thank You 17