Turkish Guidelines for the management of pregnancies with GDM OLUS API YedITEPE UNIVERSITY HOSPITAL, ISTANBUL, TURKEY

one of the largest health emergencies of the 21st century 1 in 11 adults have diabetes (415 million) By 2040, 1 adult in 10 (642 million) will have diabetes The prevalence of diabetes is increasing worldwide IDF Diabetes Atlas, 7th Edition, 2015

1 in 7 births is affected by gestational diabetes 16.2 % OF LIVE BIRTHS

HAPO: Incidence of Adverse Outcomes Increases Along Continuum N Engl J Med. 2008 May 8;358(19):1991-2002. doi: 10.1056/NEJMoa0707943. Hyperglycemia and adverse pregnancy outcomes. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA. Source Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. bem@northwestern.edu Abstract BACKGROUND: It is controversial whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. METHODS: A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter (5.8 mmol per liter) or less and the 2-hour plasma glucose level was 200 mg per deciliter (11.1 mmol per liter) or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia. RESULTS: For the 23,316 participants with blinded data, we calculated adjusted odds ratios for adverse pregnancy outcomes associated with an increase in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight above the 90th percentile, the odds ratios were 1.38 (95% confidence interval [CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively; for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI, 1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to 1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03 to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at which risks increased. Significant associations were also observed for secondary outcomes, although these tended to be weaker. CONCLUSIONS: Our results indicate strong, continuous associations of maternal glucose levels below those diagnostic of diabetes with increased birth weight and increased cord-blood serum C-peptide levels. Metzger BE, et al. Hyperglycemia and Adverse Pregnancy Outcomes. NEJM 2008;358(19):1991-2002.

Why Diagnose and Treat GDM? MATERNAL MORBIDITY Short-term Preterm labor Preeclampsia Traumatic labor Caesarian section Postoperative/postpartum infection Postoperative/postpartum hemorrhage Thromboembolism Maternal morbidity and mortality Hemorrhage Post-partum & Long-Term Failure to initiate and/or maintain breastfeeding Infection Weight retention GDM in subsequent pregnancy Future overt diabetes Future cardiovascular diseasePrevent future risks for the mother (CVD, DM II)

Why Diagnose and Treat GDM? FETAL/NEONATAL/CHILD MORBIDITY Short-term Stillbirth Neonatal death Shoulder dystocia Respiratory distress syndrome Excessive fetal growth (macrosomia, large for gestational age) Cardiomyopathy Neonatal hypoglycemia Neonatal polycythemia Neonatal hyperbilirubinemia neonatal hypocalcemia Erb’s palsy (as consequence of birth injury) Long-Term Programming and imprinting; fetal origins of disease: diabetes, obesity, hypertension, metabolic syndrome

DIABETES IN TURKEY Diabetes has become one of the major public health issues also in Turkey Rapid economic growth Increase in life expectancy Changes in lifestyle According to the recent global estimates of the World Health Organization, there will be 300 million people with diabetes by the year 2025. POSSIBLE CAUSES World Health Organization. World health statistics 2011. Geneva: WHO Press; 2011.

> 12 %

6-8%

EPIDEMIOLOGY OF DIABETES: TURKEY DATA TURDEP STUDY-1 & TURDEP STUDY-2 Turkish Diabetes Epidemiology Study Group Turkey was a country where awareness of diabetes was poor. Screening programs date back to the 1940s, and nearly 1 million people have been screened to date, but because of differing methodology and lack of standardization between studies, considerable variations in diabetes prevalence have been reported from one area to another and even in the same area over time INCREASING PREVALANCE

Cross-sectional, population-based survey, 1997-1998 N = 24,788 subjects (age ≥ 20 years, women 55%, response 85%) Glucose tolerance was classified according to WHO recommendations on the basis of 2-h blood glucose values Satman I et al. Diabetes Care, 2002

*TURDEP-1 STUDY: Satman İ, Yılmaz T and TURDEP Study Group TURDEP-1 STUDY RESULTS (> 20 YEARS OF AGE) Diyabet 7.2 % Yeni DM 32.3 % Bilinen D 67.7 % BGT 6.7 % DIABETES UNDIAGNOSED DM KNOWN DM IGT *TURDEP-1 STUDY: Satman İ, Yılmaz T and TURDEP Study Group

TURGEP-II STUDY Cross-sectional, population-based survey, 15 January to 11 June 2010. N = 26,499 subjects (age ≥ 20 years, response 87%) Fasting glucose and biochemical parameters were measured in all; then a OGTT was performed. amples from both urban and rural populations in five geographical regions corresponding to the first survey. Three provinces from each region, six counties from each province, and three urban districts and three rural villages from each county were randomly selected. Satman I et al. Eur J Epidemiol, 2013

*TURDEP-2 STUDY: Satman I and TURDEP Study Group TURDEP-2 STUDY RESULTS (> 20 YEARS OF AGE) Diabetes 13.7% (UNDIAGNOSED) 45.5% IGT 13.9 % The crude prevalence of diabetes was 16.5 % (95 % CI: 16.1–17.0); of them 45.5 % had newly diagnosed (prevalence: 7.5 %; 95 % CI: 6.3–8.7) and 54.5 % previously known (9.0 %; 7.8–10.1) diabetes (p\0.001). Among previously known diabetes 85.5 % was on anti-diabetic medications (OAD: 71.9 %, insulin: 2.2 %, insulin ? OAD: 11.4 %). *TURDEP-2 STUDY: Satman I and TURDEP Study Group

AGE-SPECIFIC DIABETES RATES TURDEP-1 AND TURDEP-II AGE GROUPS OVERALL 13.7 %, MEN 12.4 %, WOMEN 14.6 %

TURKEY MINISTRY OF HEALTH, CHRONIC DISEASES & RISK FACTORS STUDY – PHYSICAL INACTIVITY MEN INADEQUATE MODERATE ADEQUATE WOMEN INADEQUATE MODERATE ADEQUATE ANKARA, 2013 http://sbu.saglik.gov.tr/Ekutuphane/kitaplar/khrfat.pdf

Obesity rates in women & men TURDEP-II Obesity ; BMI

Rate of diabetes & prediabetes increasing in Turkey Prevalance of Diabetes(%) Percent Increase DM %90 IGT % 106 Obesity % 40 Central Obesity % 35 Hypertension % 11 15 % 64,5 %90 13.7 (16.5) 10 1997 2010 % 49,8 7.2 5 Average age ↑ 4 years, Women 6 kg,average waist 6 cm ↑ Men 8 kg, average waist 7 cm ↑ Onset of diabetes 5 years earlier Satman I et al. Eur J Epidemiol, 2013 Satman I et al. Diabetes Care, 2002

CHALLENGES IN DIAGNOSIS OF GDM IN TURKEY

1) DIAGNOSIS OF PREDIABETES ‘Isolated-IFG’ FPG levels = 5.6–6.9 mmol/L (100–125 mg/dL) but 2-hPG levels < 7.8 mmol/L ( < 140 mg/dL) Isolated-IGT 2-hPG levels 7.8–11.0 mmol/L (140–199 mg/dL) but FPG levels < 5.6 mmol/L (<100 mg/dL) Combined prediabetes (IFG + IGT) Both FPG levels 5.6–6.9 mmol/L (100–125 mg/dL) and 2-hPG levels 7.8–11.0 mmol/L (140–199 mg/dL) The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care. 2003;26:3160–7.

IMPAIRED FASTING GLUCOSE (IFG) IMPAIRED GLUCOSE TOLERANCE (IGT) TURDEP-II: Prediabetes The crude prevalence of prediabetes was 30.8 % (isolated- IFG 14.7 %, isolated-IGT 7.9 %, and combined 8.2 %). IMPAIRED FASTING GLUCOSE (IFG) IMPAIRED GLUCOSE TOLERANCE (IGT) COMBINED IFG + IGT CRUDE RATE STANDARDIZED RATE

45.5 % for TURKEY according to TURDEP-II study

MARCH, 2017

M. Hod et al. International Journal of Gynecology and Obstetrics ; 2015

This clinical practice guideline was prepared by the Diabetes and Pregnancy Study Group of Turkish Perinatology Society to clarify controversial issues in Turkey and facilitate clinical practice in the light of new scientific data obtained on pregnancy and diabetes recently.

Recommendations for screening GDM All pregnant women should be screened for GDM at 24-28 weeks of gestation [Grade C, Level3 3) If there is a high risk of GDM based on multiple clinical factors, screening should be offered at any stage in the pregnancy [Grade D, Consensus]. If the initial screening is performed before 24 weeks of gestation and is negative, rescreen between 24-28 weeks of gestation.

USING THE IADPSG criteria The rate of diagnosed GDM cases increases to 18%. More intervention What is the impact on the patient and workload of increasing the prevalence of GDM? Do we have sufficient evidence with respect to treatment benefit at the various thresholds to make an informed decision?