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1 임신성당뇨병의관리 김성훈 관동의대제일병원내과

2 내용 임신성당뇨병의정의와임상적의미 선별검사와진단 발병원인 임신중관리 분만후관리와추적관찰

3 증례 임신 28주의 32세여성 임신 27주에 50g OCT:1시간혈당이 174 mg/dl 100g OGTT: fasting-97 mg/dl, 1 hour-189 mg/dl, 2 hour-166mg/dl, 3 hour-140mg/dl 신장 164cm, 체중은 75kg ( 임신전 68kg) 혈압 110/70mmHg, 신체검사, 소변검사나다른검사소견은정상

4 임신성당뇨병의정의 Glucose intolerance of variable severity, with onset or first recognition during pregnancy Increasing prevalence of obesity and diabetes - T2DM in women of childbearing age - pregnant women with undiagnosed T2DM Diabetes at initial prenatal visit, using standard criteria overt, not gestational, diabetes (IADPSG 2010) In Korea: 2-5% of all pregnancies

5 임신부 태아 신생아 인슐린작용 혈중포도당아미노산지질 태 반 거대아불균등성장 고인슐린혈증 혼합영양소 저혈당증고빌리루빈혈증저칼슘혈증적혈구과다증 사춘기비만 내당능장애 제 2 형당뇨병

6 임신성당뇨병의임상적의미 Perinatal complications (fetal or neonatal) - excessive fetal growth (macrosomia) - shoulder dystocia, birth injury (bone fracture and nerve palsies) - hypoglycemia, hyperbilirubinemia, hypocalcemia, erythremia, poor feeding - high risk of developing glucose intolerance and obesity in the offspring at a young age Maternal complications - morbidity from operative delivery - maternal birth trauma - preterm labor - preeclampsia - a lifetime risk of diabetes mellitus

7 Frequency of perinatal complications in women with mild to moderate GDM without treatment Buchanan TA et al. Nat. Rev Endocrinol 8: 639, 2012

8 선별검사와진단검사

11 ADA: Standards of Medical Care in Diabetes Diabetes Care 36:S11-S66

12 임신성당뇨병의진단기준 당뇨병진료지침 2011, 대한당뇨병학회

14 발병원인 Autoimmune destruction of the pancreatic cells Monogenic diabetes Similarities to type 2 diabetes : β-cell defects and insulin resistance

15 Rationale for treatment of mild GDM

16 Conclusion Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman s health-related quality of life NEJM 352:24, 2005

17 NEJM 361:1339, 2009

18 임신중관리

19 Goals of management - to prevent perinatal mortality and morbidity - to achieve and maintain normoglycemia Blood glucose goals (by ADA) Fasting whole blood glucose 95 mg/dl 1-h postprandial whole blood glucose 140 mg/dl 2-h postprandial whole blood glucose 120 mg/dl

20 Patterns of glycemia in normal pregnancy Hernandez TL et al. Diabetes Care 2011;34:

21 임상영양치료 MNT: the cornerstone of Tx for GDM Goals of MNT - provide the necessary nutrients for maternal/fetal health - to maintain normoglycemia - prevent ketosis - to allow for the appropriate weight gain

22 Individualized MNT Total calories: kcal/bw (30-35 kcal/ibw) - A 30% of calorie restriction in obese women (BMI >30) (~25 kcal/kg actual weight per day) : reduce hyperglycemia and plasma TG and no increase in ketonuria Carbohydrate-restricted diet : 35-40% (by ADA), 50% in Korea (Park et al, 2001) reduce maternal blood glucose values and improve fetal outcome Carbohydrates with low GI - reduce postprandial hyperglycemia and to provide sufficient slowrelease CHO to prevent hypoglycemia between meals Small frequent meals: 3 main meals and 2 to 3 snacks

23 Goals for weight gain (1) Prepregnancy BMI Total wt.gain (kg) Rate of wt.gain(2&3tri.)kg/wk Underweight (<18.5) ( ) Normal weight ( ) ( ) Overweight ( ) ( ) Obese ( 30) ( ) Institute of Medicine, 2009

24 Goals for weight gain (2) Less weight gain is safe and has a beneficial effect on perinatal outcomes in obese women: a weight gain of 0-7 pounds was associated with the least macrosomia Cheng YW et al. Gestational weight gain and gestational diabetes mellitus: perinatal outcomes. Obstet Gynecol 112: , 2008

25 Gynecol Endocrinol 2011: 27:775-81

26 운동요법 Improve insulin sensitivity and reduce hyperglycemia Should not cause fetal distress, uterus contraction, or hypertension :upper body cardiovascular training Less than 30 minutes of low to moderate physical activity (walking and swimming)

27 검사 (surveillance) Maternal glycemia (daily SMBG) : self-monitoring of blood glucose (SMBG)- 4-7 times/day (before breakfast, 1-2hr after breakfast, lunch, and dinner) US measurement of fetal abdominal circumference : 2 nd and early 3 rd trimesters and repeated every 3-6 weeks Urine ketone : severe hyperglycemia, weight loss during treatment insufficient caloric or CHO intake (starvation ketosis) Glycosylated Hb or other circulating proteins

28 인슐린치료 When nutritional therapy fails to maintain glycemic goals or who show signs of excessive fetal growth - Two major approaches 1. glycemia criteria 2. fetal growth-based strategy (fetal AC) Human insulin (NPH and RI) and insulin analogues (lispro, aspart, premix insulin, and detemir) Insulin administration be individualized (ex, MDI and Insulin pump)

29 경구혈당강하제 A randomized clinical trial in 404 GDM mothers (glyburide vs insulin) - mean blood glucose levels were similar in two groups - similar perinatal outcomes - glyburide does not appear to cross human placenta (4% ex vivo) - in the setting of GDM, glyburide and insulin are equally effective Langer et al.nejm 343:1134, 2000

30 Rowan JA et al.nejm 358:2003, 2008

31 산과관리 Fetal surveillance - Fetal US screening for congenital anomalies (FPG >120 mg/dl or A1c 7%) - Fetal US to detect fetal macrosomia - fetal movement during the last 8-10 wks of preg - Optimal application of more intensive fetal monitoring: no data Maternal surveillance - Use of corticosteroids to enhance fetal lung maturity: intensified glucose monitoring - risk of hypertensive disorder : BP and urine protein

32 Summary of antepartum care Medical Nutritional therapy Regular exercise Maternal SMBG or fetal AC for intensified Tx Insulin remains the mainstay of Tx glyburide and metformin may be offered as an alternative

33 분만시혈당관리 Most women with GDM will not require insulin during labor Continue measuring BG When induction is planned, insulin and breakfast should be omitted in the morning and iv fluids begun (5% dextrose in half-normal saline, 100 ml/h) If BG >120 mg/dl, short-acting insulin, 1U/h iv (adjust the dosage to maintain the BG mg/dl) Insulin infusion discontinued immediately before delivery and, in most cases, will not need to be resumed postpartum

34 분만후합병증 Recurrence of GDM : ~ 50% in Korean women (Kwak SH et al, Diabetes Care 31: 1867, 2008) Development of T2DM : 30-50% within 5-10 years A higher incidence of the metabolic syndrome Early atherosclerosis (endothelial dysfunction) : increased risk of chronic hypertension and CVD

35 분만후관리 CVD risk factor assessment Breast feeding Contraception or pregnancy planning Diabetes prevention

36 Mitigation of the risk of DM The first step is to decide what type of GDM the patient had :β-cell dysfunction related to islet autoimmunity or monogenic diabetes

37 Risk of T2DM after GDM Study Year Country T2DM/GDM T2DM/no GDM RR (95%CI) Lee H et al Korea 71/620 22/ ( ) Feig et al Canada 2,874/21,823 6,628/637, ( ) Madarasz et al 1995 Hungary 21/68 0/ ( ) Gunderson et al USA 43/ /2, ( ) Vambergue et al 1992 France 53/295 1/ ( ) Lee A et al Australia 405/5,470 16/ ( ) Ferraz et al 2007 Brazil 6/70 7/ ( ) Krishnaveni et al India 13/35 8/ ( ) Morimitsu et al Brazil 7/23 0/ ( ) Jarvela et al Finland 23/435 0/ ( ) Albareda et al Spain 44/696 0/ ( ) Aberg et al Sweden 21/229 1/ ( ) Linne et al Sweden 10/28 0/ ( ) Bian et al China 15/45 1/ ( ) Ko et al China 105/801 7/ ( ) Osei et al USA 10/15 0/ ( ) Damm et al Denmark 33/241 0/ ( ) Benjamin et al USA 14/47 3/ ( ) O'Sullivan et al USA 224/615 18/ ( ) Persson et al Sweden 5/145 0/ ( ) Total 3,997/31,867 6,862/643, ( ) Bellamy et al. Lancet Decreased risk Increased risk

38 Incidence of T2DM after GDM in Koreans Free from T2DM Median T2DM free duration: 8.1 ± 0.4 years Follow-up duration (year)

39 Risk factors for conversion from GDM to type 2 diabetes Fasting glucose value on OGTT Obesity precedes pregnancy Postpartum weight gain GDM diagnosed before the 24 th week of pregnancy Relative insulinopenic response to oral glucose The requirement for insulin in pregnancy Family history of type 2 diabetes, esp on the maternal side Maternal age Parity Previous history of GDM

40 분만후혈당검사 Summary and Recommendations of the Fifth International Workshop-Conference on Gestational Diabetes Mellitus, Diabetes Care 30 (Suppl.2), 2007

41 Management of women with prior GDM Buchanan TA et al. Nat. Rev Endocrinol 8: 639, 2012

42 Prevention of T2DM in women with GDM In women with a history of GDM, Metformin and intensive lifestyle: ~50% reduction in the risk of diabetes Women with a history of GDM found to have prediabetes should receive lifestyle interventions or metformin to prevent diabetes ADA: Standards of Medical Care in Diabetes Diabetes Care 36:S11-S66

43 Future directions Risk and timeline for progression to diabetes Appropriate preventive strategies - Optimal timing and cost-effectiveness of diabetes prevention interventions - Effective ways to deliver preventive interventions

44 결론 임신성당뇨병의진단과치료는주산기합병증을감소시킨다. 임신성당뇨병여성은분만후정기적인혈당검사를시행하고당뇨 병의위험성에대한설명과예방을위한생활요법이필요하다. 임상의는임신성당뇨병여성에게당뇨와심혈관질환위험인자의 조기발견, 예방과관리에대한최신지견을적용함으로써이들의삶 을향상시킬수있다.

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract