Gestational Diabetes: An Update

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Presentation delivered at the 16th ASEAN Federation of Endocrine Societies congress in Ho Chi Minh City, Vietnam

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Gestational Diabetes: An Update

  1. 1. GESTATIONAL DIABETES: AN UPDATE Iris Thiele Isip Tan MD, MSc, FPCP, FPSEM Clinical Associate Professor, UP College of Medicine Section of Endocrinology, Diabetes & Metabolism Department of Medicine, Philippine General HospitalFriday, November 18, 11
  2. 2. 1964 1982 2008 2010 1972 1996 2003 2006 2011 MD 1st Son #1 Son #2 Here I am! birthday http://www.flickr.com/photos/yogma/3961135108/ http://www.sxc.hu/photo/533027Friday, November 18, 11
  3. 3. “For at least a generation there has been a divergence of opinions about GDM.” Robert G. Moses, MD New Consensus Criteria for GDM: Problem Solved or a Pandora’s Box Diabetes Care 2010;33(3):690-1 1964 1982 2008 2010 1972 1996 2003 2006 2011 MD 1st Son #1 Son #2 Here I am! birthday http://www.flickr.com/photos/yogma/3961135108/ http://www.sxc.hu/photo/533027Friday, November 18, 11
  4. 4. “For at least a generation there has been a divergence of opinions about GDM.” Robert G. Moses, MD New Consensus Criteria for GDM: Problem Solved or a Pandora’s Box Diabetes Care 2010;33(3):690-1 IADPSG O’Sullivan Carpenter Consensus & Mahan & Coustan criteria HAPO 1964 1982 2008 2010 1972 1996 2003 2006 2011 MD 1st Son #1 Son #2 Here I am! birthday http://www.flickr.com/photos/yogma/3961135108/ http://www.sxc.hu/photo/533027Friday, November 18, 11
  5. 5. International Implications on Association of Diabetes screening and in Pregnancy Study diagnosis of GDM Hyperglycemia Groups (IADPSG) Adverse Pregnancy Outcomes (HAPO)Friday, November 18, 11
  6. 6. Hyperglycemia Adverse Pregnancy Outcomes HAPO NEJM 2008; 358:1991-2002 large diverse population 25,505 pregnant single protocol 15 centers 9 countries Thailand, Hong Kong, SingaporeFriday, November 18, 11
  7. 7. 75-g OGTT 24-32 weeks Results unblinded if FPG >105 mg/dL 2h PG >200 mg/dL RPG >160 mg/dL any PG <45 mg/dL HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  8. 8. HAPO NEJM 2008; 358:1991-2002 Cord blood serum BW>90th %ile C-peptide >90 %ile Primary OUTCOMES Primary CS Neonatal hypoglycemia http://www.flickr.com/photos/mikewade/3267336862/ http://www.flickr.com/photos/clairity/1385780317/ http://www.flickr.com/photos/j2dread/4501366303/ http://www.flickr.com/photos/tessawatson/379265818/Friday, November 18, 11
  9. 9. OR for adverse pregnancy outcomes 1 level SD increase FPG 6.9 mg/dL (0.4 mmol/L) 1 h PG 30.9 mg/dL (1.7 mmol/L) 2 h PG 23.5 mg/dL (1.3 mmol/L) HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  10. 10. HAPO NEJM 2008; 358:1991-2002 1h PG 1.46 Fasting (95%CI 2h PG BW>90th %ile 1.39,1.53) 1.38 1.38 (95%CI (95%CI 1.32,1.44) OR 1.32,1.44) Fasting 1.55 (95%CI 1h PG 1.47,1.64) 1.46 (95%CI 1.38,1.54) 2h PG 1.37 Cord blood serum (95%CI 1.30,1.44) C-peptide >90 %ile http://www.flickr.com/photos/mikewade/3267336862/ http://www.flickr.com/photos/clairity/1385780317/Friday, November 18, 11
  11. 11. HAPO NEJM 2008; 358:1991-2002 1h PG 1.10 Fasting (95%CI 2h PG Primary CS 1.06,1.15) 1.11 1.08 (95%CI (95%CI 1.03,1.12) OR 1.06,1.15) Fasting 1.08 (95%CI 1h PG 0.98,1.19) 1.13 (95%CI 1.03,1.26) 2h PG Neonatal 1.10 hypoglycemia (95%CI 1.00,1.12) http://www.flickr.com/photos/tessawatson/379265818/ http://www.flickr.com/photos/j2dread/4501366303/Friday, November 18, 11
  12. 12. No obvious threshold at which risks increased HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  13. 13. No obvious threshold FPG mg/dL at which risks increased Category 1 <75 2 75-79 3 80-84 4 85-89 5 90-94 6 95-99 7 >100 HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  14. 14. No obvious threshold 1h PG mg/dL at which risks increased Category 1 <105 2 106-132 3 133-155 4 156-171 5 172-193 6 194-211 7 >212 HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  15. 15. No obvious threshold 2h PG mg/dL at which risks increased Category 1 <90 2 91-108 3 109-125 4 126-139 5 140-157 6 158-177 7 >178 HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  16. 16. LGA C-section Hypoglycemia C-peptide HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  17. 17. “Lack of clear thresholds and the fact that the four primary outcomes are not necessarily of equal clinical importance make direct translation of our results into clinical practice challenging.” HAPO NEJM 2008; 358:1991-2002Friday, November 18, 11
  18. 18. “... the relationship between maternal glucose levels and fetal growth and outcome appear to be a basic biologic phenomenon, and not a clearly demarcated disease state ...” Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  19. 19. “What is a challenge is to decide how much increase in risk is the point at which treatment should be initiated and what is the hope and expectation for the treatment to reduce those risks ...” Metzger B. Endocrine Today 2008Friday, November 18, 11
  20. 20. “Secondly, should the associations of glucose be weighted equally with the primary outcomes or are some more important than others? The third issue is whether all of the glucose measures are needed to identify increased risk.” Metzger B. Endocrine Today 2008Friday, November 18, 11
  21. 21. International Association of Diabetes in Pregnancy Study Hyperglycemia Groups (IADPSG) Adverse Pregnancy Outcomes (HAPO)Friday, November 18, 11
  22. 22. IADPSG encourage and facilitate research and advance education facilitate an international approach to enhancing the quality of care for women with diabetes in pregnancy http://www.sxc.hu/photo/358002 Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  23. 23. IADPSG workshop/conference June 2008 (220 delegates approx 40 countries) consensus development session (50 delegates) Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  24. 24. OR for increased neonatal body fat, LGA and cord serum C-peptide Mean glucose as reference Positive Predictive Value % for >90th %ile OR Subjects > Birth Threshold C-peptide % Body fat weight 1.75 16.1 16.2 17.5 16.6 2.0 8.8 17.6 19.7 18.8 Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  25. 25. IADPSG recommendation for diagnosis of GDM FBS 92 mg/dL Diagnosis requires only one 1h 180 mg/dL threshold value exceeded 2h 153 mg/dL Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  26. 26. IADPSG recommendation for diagnosis of GDM FBS 92 mg/dL Diagnosis requires only one 1h 180 mg/dL threshold value exceeded 2h 153 mg/dL ADA FBS 95 mg/dL 1h 180 mg/dL 2h 155 mg/dL Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  27. 27. First prenatal visit Measure FPG, A1c or random plasma glucose in all or only in high-risk Overt Diabetes in Gestational Order a 75-g Pregnancy Diabetes OGTT at 24-28 FPG > 7 mmol/L wks AOG A1c > 6.5% FPG Random PG > 5.1-6.9 mmol/L FPG 11.1 mmol/L (92-125 mg/dL) <5.1 mmol/L IADPSG Consensus Panel. Diabetes Care Mar 2010;33(3):676-82Friday, November 18, 11
  28. 28. IADPSG recommendation for diagnosis of GDM FBS 92 mg/dL 24-28 wks AOG 1h 180 mg/dL Diagnosis requires only one threshold value exceeded 2h 153 mg/dL Overt diabetes FPG >7.0 mmol/L (126 mg/dL) Coustan et al. AJOG 2010; 202(6):654.e1-654.e6Friday, November 18, 11
  29. 29. Implications on screening and diagnosis of GDMFriday, November 18, 11
  30. 30. Use of IADPSG criteria More women will be diagnosed with GDM 17.8% of pregnant women in HAPO http://www.flickr.com/photos/kkoshy/4334413228/ + 1,702 women with GDM from 2,448 to 4,150 of 23,316 pregnancies in HAPO Ryan EA. Diabetologia 2011; 54:480-6Friday, November 18, 11
  31. 31. n = 1038 50-g GCT Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  32. 32. n = 1038 50-g GCT + GCT >7.8 mmol/L n = 228 Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  33. 33. n = 1038 GCT - 50-g GCT <7.8 mmol/L n = 810 + GCT >7.8 mmol/L n = 228 Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  34. 34. n = 1038 GCT - 50-g GCT <7.8 mmol/L n = 810 + GCT >7.8 mmol/L n = 228 75-g OGTT Japan SOG criteria FPG>100 mg/dL 1h PG >180 mg/dL 2h PG >150 mg/dL Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  35. 35. n = 1038 GCT - 50-g GCT <7.8 mmol/L n = 810 + GCT >7.8 mmol/L n = 228 75-g OGTT OGTT + Japan SOG criteria >7.8 mmol/L FPG>100 mg/dL n = 25 1h PG >180 mg/dL 2h PG >150 mg/dL Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  36. 36. n = 1038 GCT - 50-g GCT <7.8 mmol/L n = 810 + GCT OGTT >7.8 mmol/L - >7.8 mmol/L n = 228 n = 203 75-g OGTT OGTT + Japan SOG criteria >7.8 mmol/L FPG>100 mg/dL n = 25 1h PG >180 mg/dL 2h PG >150 mg/dL Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  37. 37. n = 1038 GCT - 50-g GCT <7.8 mmol/L IADPSG + criteria n = 810 + GCT OGTT >7.8 mmol/L - >7.8 mmol/L 43 GDM n = 228 n = 203 75-g OGTT OGTT + 5 overt DM Japan SOG criteria >7.8 mmol/L 20 GDM FPG>100 mg/dL n = 25 1h PG >180 mg/dL 2h PG >150 mg/dL Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  38. 38. n = 1038 Total 68 GDM 172% increase GCT - 50-g GCT <7.8 mmol/L IADPSG + criteria n = 810 + GCT OGTT >7.8 mmol/L - >7.8 mmol/L 43 GDM n = 228 n = 203 75-g OGTT OGTT + 5 overt DM Japan SOG criteria >7.8 mmol/L 20 GDM FPG>100 mg/dL n = 25 1h PG >180 mg/dL 2h PG >150 mg/dL Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  39. 39. Impact on workload of changing GDM diagnostic criteria by lowering fBGL alone and with increasing 2h BGL (IADPSG) 29% increase in workload extra 366 women diagnosed ADIPS criteria fBGL >5.5 mmol/L 2h BGL >8.0 mmol/L Flack JR et al. Aus NZ J Obstet Gynecol 2010; 50:439-43.Friday, November 18, 11
  40. 40. “One approach will be to argue that we cannot cope with the change in numbers and that these new criteria should be ignored.” will leave a significant number at risk untreated... Flack JR et al. Aus NZ J Obstet Gynecol 2010; 50:439-43.Friday, November 18, 11
  41. 41. Adjust thresholds for fasting, 1h & 2h BG levels “to keep the number of women diagnosed with GDM stable ... an example of explicit rationing of medical care.” Flack JR et al. Aus NZ J Obstet Gynecol 2010; 50:439-43.Friday, November 18, 11
  42. 42. Stratify risk. “Those women diagnosed at the lower end of the ‘new’ diagnostic range may be expected to be at ‘lower risk’ and if so, their management ‘may’ be ...‘less stringent’.” Flack JR et al. Aus NZ J Obstet Gynecol 2010; 50:439-43.Friday, November 18, 11
  43. 43. OGTT n = 25 + 20 GDM >7.8 mmol/L 5 overt DM needed insulin n = 228 OGTT n = 203 75-g OGTT - >7.8 mmol/L IADPSG criteria Japan SOG criteria FPG>100 mg/dL 43 GDM 1h PG >180 mg/dL of which 5 2h PG >150 mg/dL needed insulin IADPSG “overt diabetes” diagnosis may help differentiate women who need insulin from women who do not need insulin. Morikawa M. Diab Res Clin Pract 2010; 90:339-42.Friday, November 18, 11
  44. 44. IADPSG criteria X 140 cases of LGA X 21 cases of shoulder dystocia X 16 cases of birth injury of 23,316 pregnancies in HAPO cohort Ryan EA. Diabetologia 2011; 54:480-6 http://www.sxc.hu/photo/249796Friday, November 18, 11
  45. 45. IADPSG criteria X 140 cases of LGA X 21 cases of shoulder dystocia X 16 cases of birth injury of 23,316 pregnancies in HAPO cohort Modest outcomes? Ryan EA. Diabetologia 2011; 54:480-6 http://www.sxc.hu/photo/249796Friday, November 18, 11
  46. 46. n = 1038 Total 68 GDM 172% increase GCT - 50-g GCT <7.8 mmol/L IADPSG + criteria n = 810 + GCT OGTT >7.8 mmol/L - >7.8 mmol/L 43 GDM n = 228 n = 203 75-g OGTT OGTT + 5 overt DM Japan SOG criteria >7.8 mmol/L 20 GDM FPG>100 mg/dL n = 25 1h PG >180 mg/dL 2h PG >150 mg/dL Morikawa M. Diab Res Clin Pract 2010;90: 339-42.Friday, November 18, 11
  47. 47. OGTT n = 25 + 5 overt DM + GCT >7.8 mmol/L 20 GDM n = 228 OGTT n = 203 75-g OGTT - >7.8 mmol/L 43 GDM Japan SOG criteria FPG>100 mg/dL IADPSG criteria 1h PG >180 mg/dL no specific treatment 2h PG >150 mg/dL for GDM Morikawa M. Diab Res Clin Pract 2010;90 339-42.Friday, November 18, 11
  48. 48. OGTT n = 25 + 5 overt DM + GCT >7.8 mmol/L 20 GDM n = 228 OGTT n = 203 75-g OGTT - >7.8 mmol/L 43 GDM Japan SOG criteria FPG>100 mg/dL IADPSG criteria 1h PG >180 mg/dL no specific treatment 2h PG >150 mg/dL for GDM 6 infants >3600 g (14%) p=0.021 vs non-GDM 3.8% (n=160) Number Needed to Treat (NNT) 1/(0.14-0.038) = 9.8 Morikawa M. Diab Res Clin Pract 2010;90 339-42.Friday, November 18, 11
  49. 49. Nurses, dietitians & physicians Glucose monitoring Therapy of diabetes Ryan EA. Diabetologia 2011; 54:480-6Friday, November 18, 11
  50. 50. Cost-effective strategy based on risk GDM risk <1%: no screening/treatment strategy 1-4.2%: FPG followed by OGTT >4.2%: OGTT alone Round JA et al. Diabetologia 2011; 54:256-63 Nurses, dietitians & physicians Glucose monitoring Therapy of diabetes Ryan EA. Diabetologia 2011; 54:480-6Friday, November 18, 11
  51. 51. RR for developing gestational diabetes by ethnicity (adjusted for age, BMI and parity; white as reference) UK Data (1992) RR (95%CI) Black 3.1 (1.8 to 5.5) South East Asian 7.6 (4.1 to 14.1) Indian 11.3 (6.8 to 18.8) Dornhorst A, Paterson CM, Nicholls JSD, et al. High prevalence of gestational diabetes in women from ethnic minority groups. Diabetic Medicine 1992; 9:820–5.Friday, November 18, 11
  52. 52. AFES Study Group on Diabetes in Pregnancy (ASGODIP) ASGODIP protocol 1-step (high-risk) Prevalence (%) 75-g OGTT Indonesia 16 2h cut-off 140 mg/dL Malaysia 13 Philippines n/N Philippines 14 Low risk 35/853 Singapore 10 High risk 136/350 Thailand 13 171/1203 Overall ASEAN 13 14.2% Litonjua AD et al. AFES Study Group on Diabetes in Pregnancy: Preliminary Data on Prevalence. PJIM 1996:34:67-68.Friday, November 18, 11
  53. 53. Increased prevalence of GDM using the IADPSG criteria “can only be justified if it is shown convincingly that pregnancy outcomes are improved.” Holt RIG et al. Diabete Med 2011; 28:382-5.Friday, November 18, 11
  54. 54. Landon et al NEJM 2009; M 361:1339-48. O Randomized Composite of controlled I stillbirth/ trial perinatal P Intervention death and (n=485) neonatal diet CBG insulin complications vs hyperbilirubinemia routine care hypoglycemia (n=473) hyperinsulinemia birth trauma “mild” GDM 24-31 wks AOG Landon MB et al. A multicenter, randomized trial of treatment for mild gestational diabetes. NEJM 2009; 361:1339-48.Friday, November 18, 11
  55. 55. Composite endpoint RR 0.87 (95% CI 0.72-1.07), p=0.14 Landon et al NEJM 2009; M 361:1339-48. O Randomized Composite of controlled I stillbirth/ trial perinatal P Intervention death and (n=485) neonatal diet CBG insulin complications vs hyperbilirubinemia routine care hypoglycemia (n=473) hyperinsulinemia birth trauma “mild” GDM 24-31 wks AOG Landon MB et al. A multicenter, randomized trial of treatment for mild gestational diabetes. NEJM 2009; 361:1339-48.Friday, November 18, 11
  56. 56. Composite endpoint RR 0.87 (95% CI 0.72-1.07), p=0.14 Landon et al NEJM 2009; M 361:1339-48. O Randomized controlled I trial P Intervention (n=485) diet CBG insulin vs routine care (n=473) “mild” GDM 24-31 wks AOG Landon MB et al. A multicenter, randomized trial of treatment for mild gestational diabetes. NEJM 2009; 361:1339-48.Friday, November 18, 11
  57. 57. Composite endpoint RR 0.87 (95% CI 0.72-1.07), p=0.14 Landon et al NEJM 2009; M 361:1339-48. O Randomized LGA infants controlled I RR 0.49 trial P Intervention (95%CI 0.32-0.76) p<0.001 (n=485) diet CBG insulin BW >4000 g vs RR 0.41 routine care (95%CI 0.26-0.66) (n=473) p<0.001 “mild” GDM 24-31 wks AOG Landon MB et al. A multicenter, randomized trial of treatment for mild gestational diabetes. NEJM 2009; 361:1339-48.Friday, November 18, 11
  58. 58. ACHOIS Crowther et al. NEJM 2005; M 352:2477-86. O Randomized controlled I Serious trial perinatal P Intervention complications (n=490) death diet CBG insulin shoulder dystocia vs bone fracture nerve palsy routine care (n=510) GDM 24-28 wks AOG Crowther CA et al. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. NEJM 2005; 352:2477-86.Friday, November 18, 11
  59. 59. Any serious perinatal complication ACHOIS Adj RR 0.33 (95% CI 0.14-0.75), p=0.01 Crowther et al. NEJM 2005; M 352:2477-86. O Randomized controlled I Serious trial perinatal P Intervention complications (n=490) death diet CBG insulin shoulder dystocia vs bone fracture nerve palsy routine care (n=510) GDM 24-28 wks AOG Crowther CA et al. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. NEJM 2005; 352:2477-86.Friday, November 18, 11
  60. 60. OGTT is poorly reproducible Diagnosis based on a single test, on a single abnormal value Ryan EA. Diabetologia 2011; 54:480-6 http://www.flickr.com/photos/craigoneal/4084388198/Friday, November 18, 11
  61. 61. report used an adjustment (Model 1) for many of the expected confounders (age, alcohol, smoking, sex etc.), and Greater impact of maternal BMI on also a model (Model 2) that adjusted for fasting plasma OR for LGA than maternal glucose except highest glucose category a b 8,000 5 ● 6,000 Model 1 BMI Women (n) 4 ▲ 4,000 Model 2 BMI OR 3 2 ◆ Maternal FG 2,000 1 0 0 1 2 3 4 5 6 7 1 2 3 Glucose category Glucos <22.6 22.6− 28.5− 33.0− 37.5− 42.0 28.4 32.9 37.4 41.9 BMI category (Kg/m2) Fig. 1 a Relationship of the OR for an infant of birthweight >90th Model 1: Adjusted for age, alcohol, smoking, sex, etc. HAPO Model 2: Adjusted for mean FG and MAP 2 percentile vs the BMI in categories (reference group BMI <22.6 kg/m Ryan EA. Diabetologia 2011; 54:480-6 [4]) or maternal fasting glucose in categories from HAPO (diamonds;Friday, November 18, 11
  62. 62. roup examined the role Fig. 3). It is also noteworthy that at category 5 (equivalentmary outcomes [4]. This to the IADPSG cut-off criteria, accepting that some cases in l 1) for many of of women hadwill lie above these cut-offs within category 5) Majority the category 5 Most cases of LGA occur smoking, sex etc.),levels women below these in normal maternalrepresented glucose and < Cat. 3 cut-offs who had LGAsted for fasting glucose78% of all women giving birth to LGA. (mean plasma level) glycemia b c 8,000 700 600 6,000 500 Women (n) Women (n) 400 4,000 300 2,000 200 100 0 0 1 2 3 4 5 6 7 1 2 3 4 5 6 7 Glucose category Glucose category 78% of LGA born to women ☐ Participants categories is also shown (black diamonds). IADPSG participants not fulfilling b Number of criteria infant of birthweight >90th (see text for details). The relationship for maternal fasting glucose 2nce group BMI <22.6 kg/m ies from HAPO (diamonds; in each category of glucose in HAPO (white bars), with number of ■ Participants with LGA infants lucose [2]). a The BMIcles) or model 2 (triangles) mothers with LGA infants (black bars). c Number of participants in each category of glucose who had LGA infants HAPO Ryan EA. Diabetologia 2011; 54:480-6 Friday, November 18, 11
  63. 63. Diagnosis of GDM identifies women at risk of type 2 diabetes GDM independent risk factor for diabetes in Filipino-Americans RR 21.65 (95%CI 6.73-69.67) IADPSG criteria may overestimate risk of diabetes Cuasay et al. Diabetes Care 2001;24(12):2054-8Friday, November 18, 11
  64. 64. IADPSG Consensus Approved by ADA ACOG did not approve ACOG Committee on Obstetric Practice. Screening & Diagnosis of Gestational Diabetes Mellitus. Obstetrics & Gynecology 2011; 118(3):751-3Friday, November 18, 11
  65. 65. Philippine Diabetes CPG has partially adopted the IADPSG consensus by endorsing the HAPO-derived thresholds for the 75-g OGTT.Friday, November 18, 11
  66. 66. International Implications on Association of Diabetes screening and in Pregnancy Study diagnosis of GDM Hyperglycemia Groups (IADPSG) Adverse Pregnancy Outcomes (HAPO)Friday, November 18, 11
  67. 67. THANK YOU http://www.endocrine-witch.net isiptan@gmail.comFriday, November 18, 11

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