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제 26 차대한당뇨병학회춘계학술대회 11 May, 2013 ICC, Jeju, Korea What are the appropriate screening and diagnostic methods for gestational diabetes in Korean women? 서울의대 분당서울대학교병원 내과장학철

임신성당뇨병 Gestational diabetes mellitus is defined as glucose intolerance of variable severity with onset or first recognition during the present pregnancy. Incidence: 5% in Korean Women Maternal hyperglycemia Adverse pregnancy outcome Diabetic Fetopathy 4725 g 3250 g

Diagnosis of Overt Diabetes Mellitus in Pregnancy: Threshold Values Diagnosis of Overt Diabetes Mellitus in Pregnancy Measure of glycemia FPG A1C Consensus threshold >7.0 mmol/l (126 mg/dl) >6.5% (DCCT/UKPDS standardized) Random plasma glucose (RPG) >11.1 mmol/l (200 mg/dl) confirmed* *Confirm RPG with FPG or A1C IADPSG, Diabetes Care 2010; 33:676-82

The incidence of GDM is increasing in Korea Year Delivery(n) GDM(n) Incidence(%) 2002 8,627 344 4.0 2003 9,464 338 3.6 2004 8,972 250 2.8 2005 8,112 172 2.1 2006 7,725 222 2.9 2007 7,730 325 4.2 2008 7,112 329 4.6 2009 6,352 333 5.2 2010 6,694 303 4.5 2011 6,542 356 5.4 Total 77,330 2,972 3.8 김문영, 제일병원

연도별고령산모비율 (%) % 제일병원 통계청 고령산모가늘어나면서임신중당뇨병으로병원을찾는사람이매년 27% 씩증가 ( 국민건강보험공단, 2012.10.9) 김문영, 제일병원

임산부의날, MBN News 고령산모가늘어나면서임신중당뇨병으로병원을찾는사람이매년 27% 씩증가 ( 국민건강보험공단, 2012.10.9)

Contents Current diagnostic approach for GDM Detection and diagnosis of GDM in Korea Case presentation

Current Screening and Diagnostic Test for GDM Two step approach 50 g glucose challege test Cutoff -130, 135, 140 mg/dl 100 g glucose tolerance test NDDG criteria Carpenter-Coustan criteria One step approach WHO IADPSG

Glucose Thresholds for the Diagnosis of GDM Criteria NDDG (100 g) C-C (100 g) WHO (75 g) IADPSG (75 g) Fasting, mg/dl 1-h, mg/dl 2-h, mg/dl 3-h, mg/dl 105 190 165 145 95 180 155 140 110 140 92 180 153 C-C = Carpenter & Coustan; NDDG = National Diabetes Data Group; WHO = World Health Organization; IADPSG = International Association of Diabetes and Pregnancy Study Groups

HAPO Study Observational study Glucose tolerance status using 75 g OGTT at 24 to 32 weeks during pregnancy in 25,505 pregnant women from 15 centers in 9 countries Increasing maternal glucose levels were related to increased infant birth weight, body fat, and cord C- peptide > 90th percentile, and increased primary cesarean delivery rates. In addition, these women also had increased risks for premature delivery, preeclampsia, shoulder dystocia or birth injury, and hyperbilirubinemia. N Engl J Med 358:1991 2002, 2008

HAPO study: Associations btw Maternal Glucose & 1 Outcomes Birth Weight > 90th Percentile Primary C-Section Frequency (%) 30 25 20 15 10 5 0 1 2 3 4 5 6 7 Fasting One Hour Two Hour Frequency (%) 35 30 25 20 15 10 5 0 1 2 3 4 5 6 7 Fasting One Hour Two Hour Glucose Categories Glucose Categories Clinical Hypoglycemia Cord C-Peptide >90th Percentile Frequency (%) 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 1 2 3 4 5 6 7 Fasting One Hour Two Hour Frequency (%) 35 30 25 20 15 10 5 0 1 2 3 4 5 6 7 Fasting One Hour Two Hour Glucose Categories Glucose Categories

Plasma Glucose Concentrations at Specified OR Glucose Odds Ratio mg/dl* 1.5 1.75 2.0 FPG 90 92 95 1-Hr PG 167 180 191 2-Hr PG 142 153 162 *Mean of threshold values for birthweight, cord serum C-peptide, % body fat >90 th percentile

Frequencies of Outcomes: Glucose Values < or >Threshold Outcome % All Values < Threshold % Any > 92/180/153 (5.1/10.0/8.5) Birthweight >90 th percentile 8.3 16.2 Cord C-peptide >90 th percentile 6.7 17.5 % Body fat >90 th percentile 8.5 16.6 Preeclampsia 4.5 9.1 Preterm birth (<37 weeks) 6.4 9.4 Shoulder dystocia/birth injury 1.3 1.8 Primary Cesarean section 16.8 24.4

Adopting IADPSG criteria Patients Fasting state, wait time of 2 hours Increasing women with GDM Considerable inconvenience (SMBG, Education, US, etc.) Providers Additional clinical resources & services Workload would increase approximately 30 percent 1 million more clinic visits & prenatal testing in U.S.

Adopting IADPSG criteria Health Care Systems Additional outpatient visits and testing Increased time spent on labor and delivery suites due to more frequent inductions & cesarean deliveries. Direct medical and patient time costs would be higher Annual cost in the U.S. for the care of GDM x 3

Does treatment modify the health outcomes of mothers with GDM and their offspring? Very few studies NICHD RCT*: treatment of GDM reduced the risk for macrosomia, hypertensive disorders of pregnancy, and shoulder dystocia. Treatment of GDM did not increase the risk of cesarean delivery. Results were not consistent among studies for maternal weight gain and risk for induction of labor. Lack of evidence: treatment of GDM on birth trauma, BMI at delivery, and long-term maternal outcomes including T2DM, obesity, and hypertension. *Landon MB et al. NEJM 361:1339-48, 2009

Does treatment modify the health outcomes of mothers with GDM and their offspring? A 50 percent reduction in macrosomia in infants born to mothers who received treatment for GDM. No sufficient data available to conclude whether treatment of GDM modifies neonatal morbidities such as prematurity, admission to neonatal intensive care units, or mortality.

Treatment of mild GDM Reduces Adverse Outcome* Outcome Not treated NICHD RCT Treated P BW >90 th percentile 14.5 7.1 <0.001 C-peptide >95 th percentile 22.8 17.7 0.07 NICU admission 11.6 9.0 0.19 Shoulder Dystocia 4.0 1.5 0.02 Preeclampsia 5.5 2.5 0.02 *Landon MB et al. NEJM 361:1339-48, 2009 * FPG <95 mg/dl, a 1-hr value between 180 and 199 and a 2-hr value between 155 and 199 were eligible

What are the harms of increased diagnosis of GDM? Patients short-term stress and anxiety Over-diagnosis of GDM may lead to the medicalization of pregnancy. Considerable variability in the 2-hour glucose tolerance test Anti-diabetic medication hypoglycemia Higher induction of labor rates in women with GDM Cesarean rates may be higher in women given the diagnosis of GDM.

NATIONAL INSTITUTES OF HEALTH CONSENSUS DEVELOPMENT CONFERENCE Several criteria need to be fulfilled for adopting IADPSG recommendation: There should be evidence that the additional women who are identified by the one-step approach have an increased frequency of maternal and/or perinatal morbidities. There should be evidence that these morbidities can be decreased by intervention. There should be evidence that the benefits of the decrease in morbidities outweigh the harms incurred (including maternal, perinatal, and societal). NIH, March 4 6, 2013

KDA 임신성당뇨병진료지침 진단기준 1. 첫번째산전방문검사시다음중하나이상을만족하면기왕의당뇨병이있는것으로진단한다. [E] 1-1. 공복혈장혈당 126 mg/dl 1-2. 무작위혈장혈당 200 mg/dl 1-3. 당화혈색소 6.5% 2. 임신 24-28주사이에시행한 2시간 75 g 경구당부하검사결과다음중하나이상을만족하는경우임신성당뇨병으로진단할수있다. [E] 2-1. 공복혈장혈당 92 mg/dl 2-2. 당부하 1시간후혈장혈당 180 mg/dl 2-3. 당부하 2시간후혈장혈당 153 mg/dl 3. 기존의 2단계접근법으로 100 g 경구당부하검사를시행한경우는다음기준중두가지이상을만족하는경우임신성당뇨병으로진단한다. [E] 3-1. 공복혈장혈당 95 mg/dl 3-2. 당부하 1시간후혈장혈당 180 mg/dl 3-3. 당부하 2시간후혈장혈당 155 mg/dl 3-4. 당부하 3시간후혈장혈당 140 mg/dl

임신성당뇨병소연구회 (KDPSG) 회장 : 관동의대제일병원김문영 간사 : 최성희, 한성희 Pregnancy outcome in women with gestational diabetes mellitus by IADPSG criteria ( 다기관연구 : 2013/3-) Determine whether the additional women categorized as having diabetes by the IADPSG criteria, who would be considered normal in the C-C criteria, are increased risk for adverse pregnancy outcome.

Case Presentation Case 1 여자 / 36 세 외부병원에서임신성당뇨병으로진단받고내분비내과를방문. GCT: 157 mg/dl 100 g OGTT: 112-155-160-139 mg/dl (capillary) V/S : SBP 123 mmhg, DBP 78 mmhg, PR 102/min 신장 163 cm, 현재체중 65 kg ( 임신전 60 kg) 산과력 : 0-0-0-0 현재임신 26 주 당뇨병가족력 : 없음 23

질문 진단은? GDM? 어떤검사가필요할까?

Case 1 100 g OGTT (27 wks) 89-174-114-101 mg/dl Assessment NGT Recommendation: Regular diet & exercise 25

Case Presentation Case 2 34 세임신부 이전특이병력없던 34 세산모가외부병원에서시행한혈당검사에서이상소견을보여내분비내과를방문. Outside glucose test : 107 mg/dl V/S : SBP 117 mmhg, DBP 71 mmhg, PR 94/min 신장 156 cm, 현재체중 61 kg (BMI 25.1) 산과력 : 2-0-1-1 1 st baby: male, 2.6 kg, 37 weeks 현재임신 13 주 가족력 : 아버지 - 당뇨병 임신전체중 : 61 kg 26

질문 진단은? IFG GDM 어떤검사가필요할까?

Case 2 Lab test FPG 77 mg/dl, A1C 5.5% C-peptide 1.3 ng/ml, insulin 12.1 uiu/ml Lipid Panel 222-162-60-144 mg/dl BUN 10 mg/dl, Cr 0.55 mg/dl Ca9.1 mg/dl, P 3.9 mg/dl, Uric acid 4.0 mg/dl AST/ ALT 21/26 IU/L Assessment NGT Recommendation: Screening test for GDM at 24-28 wks 28

Case Presentation Case 3 29세임신부, 임신28주 임신성당뇨병으로진단받아의뢰됨 50 g GCT: 246 100 g OGTT: 146-272-264-not done (Capillary) 산과력 : 0-0-0-0 당뇨병가족력 : 아버지 V/S SBP, 110; DBP, 64 mmhg; PR(/min) 96 신장 : 160.3 cm, 임신전몸무게 : 63 kg, 현재체중75 kg

질문 진단은? GDM Overt diabetes in pregnancy 어떤검사가필요할까?

Lab test Case 3 FPG 132 mg/dl, A1C 6.7% Assessment GDM B1 Overt diabetes in pregnancy GDM education and insulin therapy 31

감사합니다.

Pregnancy outcome in Korean women stratified by GCT and OGTT Preterm delivery (<37wk) Screen negative (n=2120) Screen positive, Normal OGTT (n=545) GDM by C- C criteria (n=37) GDM by NDDG criteria (n=74) P-value 71(3.3%) 20(3.7%) 3(8.1%) 7(9.5%)* <0.05 Total C-section 642(30.3%) 201(36.9%)* 18(48.6%)* 41(55.4%)* <0.001 Preeclampsia 9 (0.4%) 11 (2.0%)* 2 (5.4%)* 6 (8.1%)* <0.001 Gestational age at delivery (week) 39.5±1.5 39.4±1.4* 39.0±1.5* 38.8±1.4* <0.01 Apgar score (1 min) 8.5±1.0 8.5±1.0 8.4±0.9 8.4±0.9 0.42 Apgar score (5 min) 9.7±0.7 9.7±0.7 9.6±0.7 9.6±0.7 0.73 Birth weight (g) 3301±450 3360±435* 3379±461 3464±532* <0.001 LGA infant 287(13.5%) 88(16.1%) 10(27.0%)* 25(33.8%)* <0.0001 Macrosomia (>4,000 g) 106(5.0%) 29(5.3%) 2(5.4%) 10(13.5%)*.<0.05 * P<0.05 compared with women with screen negative C-C criteria: Carpenter-Coustan Criteria ( 당뇨병 28:122,2004)