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Gestational Diabetes Mellitus: Prevalence, Risk Factors Maternal and Infant Outcomes. Professor Bagher Larijani Professor of Internal Medicine & Endocrinology Head of EMRC. Endocrine and Metabolism Research Center (EMRC) Tehran University of Medical Sciences(TUMS).
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Gestational Diabetes Mellitus: Prevalence, Risk Factors Maternal and Infant Outcomes Professor Bagher Larijani Professor of Internal Medicine & Endocrinology Head of EMRC Endocrine and Metabolism Research Center (EMRC) Tehran University of Medical Sciences(TUMS)
Classification of Diabetes Mellitus Type 1 : - Immune mediated - Idiopathic Type 2 : - Insulin resistance - Relative insulin deficiency Other specific types: - Genetic defect of beta-cell function or in insulin action - Diseases of the exocrine pancreas, endocrinopathies - Induced: Drug, Infections, uncommon immune-mediated diabetes - Other genetic syndromes Gestational Diabetes Mellitus American Diabetes Association: Economic consequences of diabetes mellitus in the US in 1997. Diabetes Care 21:296, 1998 EMRC
GDM Gestational Diabetes Mellitus (GDM) is defined as: Carbohydrate intolerance of varying severity with the first recognition of onset occurring during pregnancy American Diabetes Association: Clinical practice Recommendations, Diabetes Care, 21, 1, S60, 1988
GDM Gestational Diabetes Mellitus is a common metabolic abnormality affecting pregnant women
Pathogenesis of GDM • Decreased tissue sensitivity to insulin • Impaired insulin – insulin receptor binding • Impaired intracellular insulin signaling • Increased insulin degradation • Impaired -cell function • Autoimmune destruction of pancreatic • -cells Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000
Reasons for Varying frequency of GDM around the world Ethnicity Pattern of NIDDM Screening strategy Screening & Diagnostic criteria Environment & Lifestyle
GDM Prevalence In Different Populations Country /population Prevalence% U.S All ethnicities 4 Zuni Indian 14.3 Chinese 7.3 Hispanics 4.2 Australia Australian-born 4.3 Indian-born 15 Vietnam –born 7.3
Prevalence of GDM as a percentage of all pregnancies Percent Epidemiology of glucose intolerance and GDM in women of child bearing age, Diabetes Care, 21, 1998
Frequency of GDM Regarding Ethnicity, Screening Method, And Diagnosis Criteria • The frequency of GDM according to ethnic group diagnosed using a50-g OGTT ,and 75-g OGTT (WHO criteria) Diabetes Care Vol 21 Suppl 2 B43 1998
Screening for GDM Much controversy exists regarding the screening strategy and diagnostic thresholds of GDM Increasing health care cost Limited resources Must pay attention to the
Screening Strategy Universal Selective based on Performing GCT in all pregnant women Obesity Age 25 years familial diabetes poor obstetric outcome abnormal glucose metabolism High GDM prevalence ethnic groups Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000
Sensitivity of Various Screening Protocols ACOG: The American college of obstetricians and Gynecologists Screening of high risk and general population for GDM, Clinical application and cost analysis. Diabetes, 34, 2, 24-27, 1985
Diagnostic Criteria for GDM Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000
Complications Maternal Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000 Obstetrical complications with GDM. Effect of maternal weight. Diabetes, 40, 2:79, 1991
Complications Fetal & Neonatal Macrosomia Organomegaly Prenatal mortality Neonatal hypoglycemia Hypocalcaemia Hyper bilirubinemia Polycythemia Transient tachypnea RDS Poor Apgar LGA infants Still birth Abortion
Complications • Recurrent GDM 30 % - 60 % • Diabetes type 2 5 to 16 years: 17 % - 63 % • Impaired glucose tolerancein the offspring: Age IGT ≤ 5 years 1.2 % 5 - 9 years 5.4 % 10 - 16 years 19.6 %
Monitoring • Daily SMBG • Urine ketone (insufficient caloric or carbohydrate intake) • Urine glucose (is not useful in GDM) • Urine protein & BP (Hypertensive disorders) • Glycohemoglobin • Fructosamine or Glycated albumin (in patients with hemoglobinopathies) • Maternal serum a-fetoprotein (after 16 wk) • Daily fetal movement counting by mother (after 28 wk) • Biophysical testing: (after 34 wk) • 2 × weekly NST. • or weekly CST. • or weekly biophysical profile. • Amniocentesis & delivery • phosphatidy glycerol • L/S ( > 2 the patient suffer HMD) Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000 EMRC
Management Antepartum Peripartum Medical Nutrition Therapy (MNT): • Cesarean Section: • GDM alone dose not mandate C/S • Macrosomic fetus (prevent shoulder dystocia) • Maternal glucose levels should be controlled: • Targeted blood glucose: 80-110mg/dl • Insulin: • . Usual insulin dose on the evening before induction. • . Omit morning insulin dose on day of delivery. • . On day of delivery dextrose infusion & if necessary, an intravenous insulin infusion FBS < 95mg/dl more likely to achieve good glycemic control after 2 weeks of dietary therapy. BMI > 30 we should recommend 30 – 33 % calorie restriction (25kcal/kg & 35-40% carbohydrates) Exercise: Start or continue a program of moderate exercise. Insulin • Human Insulin should be used • SMBG should guide the dose & timing of the Insulin regimen. • The use of insulin analogs has not been adequately tested in GDM. • Based on previous studies, oral glucose-lowering agents are not recommended during pregnancy. • Fructosamine levels correlated significantly with both fasting & mean glucose levels over 2-week intervals. Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000
Multicenter Survey of GDM • 2416 pregnant women • Five hospital clinics in Tehran • Universal Screening • GCT* 130 mg /dl (Positive) • GTT100-gr 3-hour (diagnostic test) * Glucose Challenge Test Iranian Journal of Endocrinology and Metabolism, 1999, Vol 1, No 2, 125-133 Journal of Endocrinology, Abstract Supplement, 19th Joint Meeting of the British Endocrine Societies, with the European Federation of Endocrine Societies, 13-16 March 2000, p.124 EMRC
Multicenter Survey of GDM • Carpenter & Coustan criteria • Obstetrics & Family history • Complete physical examinations • Followed up until delivery • OGTT 75-gr 6-12 weeks after delivery Iranian Journal of Endocrinology and Metabolism, 1999, Vol 1, No 2, 125-133 Journal of Endocrinology, Abstract Supplement, 19th Joint Meeting of the British Endocrine Societies, with the European Federation of Endocrine Societies, 13-16 March 2000, p.124 EMRC
Universal Screening • Performing blood glucose testing: • At 24 - 28 wk: all pregnant women • Before 24 wk: high risk pregnant women • Repeat after 32 wk: • - Age > 30 years • - Impaired GTT in one of the venous • plasma concentrations • - Symptoms of hyperglycemia Screening for GDM: optimum timing and criteria for retesting. Diabetes 34, 2:21-23, 1985 Clinics in laboratory medicine, 21.1 March 2001, 173-192 Diabetes Care 23.1, ADA clinical practice recommendation 2000 EMRC
Universal Screening GCT 50 g (first visit with RF) GCT 50 g OGTT 100 g At 24 – 28 wk all Pregnant women GDM OGTT 100 g GCT at 32 – 36 wk GDM OGTT No GDM - + - + - + High risk - High risk + + - + - Screening for GDM: optimum timing and criteria for retesting. Diabetes 34, 2:21-23, 1985 Diabetes Care 23.1, ADA clinical practice recommendation 2000
Multicenter SurveyThe prevalence of IGT and GDM Iranian Journal of Endocrinology and Metabolism, 1999, Vol 1, No 2, 125-133 Journal of Endocrinology, Abstract Supplement, 19th Joint Meeting of the British Endocrine Societies, with the European Federation of Endocrine Societies, 13-16 March 2000, p.124
Risk Factors for Gestational Diabetes Mellitus
Association of Risk Factors with GDM Risk factors • Obesity • Family Hx. Of DM • Age 25 • History of poor obstetric outcome • History of abnormal glucose metabolism Iranian Journal of Endocrinology and Metabolism, 1999, Vol 1, No 2, 125-133 Journal of Endocrinology, Abstract Supplement, 19th Joint Meeting of the British Endocrine Societies, with the European Federation of Endocrine Societies, 13-16 March 2000, p.124
Symptoms Associated With GDM and Normal Pregnancy Symptoms: Polyuria, Hyperhidrosis, Polydipsia, Polyphagia 31% of GDM patients were Asymptomatic 52% of Normal pregnant women were symptomatic Iranian Journal of Endocrinology and Metabolism, 1999, Vol 1, No 2, 125-133 Journal of Endocrinology, Abstract Supplement, 19th Joint Meeting of the British Endocrine Societies, with the European Federation of Endocrine Societies, 13-16 March 2000, p.124 EMRC
Universal Screening Threshold 130 mg/dL 140 mg/dL 15.7% Cost 12% sensitivity
Selective Screening 14% Sensitivity 130 mg/dL Cost 28.6% Threshold Sensitivity 23% 140 mg/dL Cost 37%
Outcome GDM Patients Controls Odds Ratio (95%CI) P-value P (%) 95%CI P (%) 95%CI Caesarean section 47.13 36.33-58.13 28.1 26.71-29.52 2.28 (1.48-3.49) 0.0002 Macrosomia 16.09 9.09-25.52 9.00 8.13-9.93 1.93 (1.08-3.47) 0.0374 Hypoglycemia 11.49 5.65-20.12 3.90 3.32-4.55 3.2 (1.62-6.3) 0.0011 Hypocalcemia 6.90 2.57-14.41 2.70 2.22-3.25 3.05 (1.29-7.16) 0.0195 Hyperbilirubinemia 12.64 6.48-21.5 7.4 6.61-8.26 1.81 (0.95-3.4) 0.1031 Pregnancy Outcome in Women with GDM and Controls
Maternal outcome OGTT 75-gr 6-12 weeks after delivery Postpartum Diabetes Mellitus : 7.3% Impaired Glucose Tolerance : 18.4%
The best predictors of postpartum diabetes and IGT • Fasting blood glucose level • Maternal obesity • Early gestational age at GDM diagnosis • Gestational requirement for insulin
The Prevalence of DM and IGT in Different Areas of IRAN (WHO Criteria 1985)
Prevalence of Diabetes Mellitus in IRAN 14.5 - 22.5 % of the people over 30 years have IGT or DM. 25 % of people with IGT will lead to Diabetes. EMRC
Prevalence of GDM as a percentage of all pregnancies Percent Epidemiology of glucose intolerance and GDM in women of child bearing age, Diabetes Care, 21, 1998
Cost-Effectiveness For every dollar spent on the Slightly more expensive postprandial monitoring strategy ,approximately $3 would be saved in adverse outcome costs
For every additional dollar spent on preconception care of diabetes $1.86 could be saved in direct medical cost for the offspring
The rate of risk factors show significant difference between GDM patients and normal pregnant women But High Prevalence of GDM among pregnant women without any risk factor suggests revision in the Risk Factors for GDM screening.
Approximately one fourth of GDM patients were experienced IGT or overt diabetes in the early postpartum period.
As conclusion: • GDM is prevalent in Iran • The Burden of GDM is significant and needs more attention • Universal screening seems more cost effective in Iran • We need a national strategy to manage this disease
National program of GDM • Large cohortstudy designed and conducted by EMRC with cooperation of CDC,Undersecretary for Health of MOH • Target areas include Tehran, Mazandaran, Ardabil, Boushehr, and Esfahan Provinces.
Objectives of program • Determine the prevalence of GDM in Iran • Evaluate the risk factors for GDM • Evaluate the complications of GDM • Recommend the most appropriate method for screening and treatment of GDM (based on ethnic and economic condition of Iran) • Compare different methods for the screening, diagnosis and treatment of GDM • Establishment of combined GDM clinics in all provinces
Summary of EMRC activities about diabetes • Performing 27 research projects • Performing 19 graduate thesis • Publishing 24 papers • Presenting 95 abstracts in seminars • Editing 5 books • Publishing 30 educational pamphlets • Publishing the Iranian Journal of Diabetes and Lipid Disorders • Conducting 4 workshops for physicians • Conducting 4 seminars • Conducting 4 educational camps for diabetic children
Summary of EMRC activities about diabetes • Establishment of diabetes polyclinic with 1200 registered patients • Establishment of GDM clinic • Establishment of Diabetes Hotline • Strategic planning for NCDs including diabetes • Establishment of National Diabetes Network • National program of GDM • National program of pancreas and islet transplantation