Journal Club

1. Journal Club Lowe WL Jr, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, McCance D, Hamilton J, Nodzenski M, Talbot O, Brickman WJ, Clayton P, Ma RC, Tam WH, Dyer AR, Catalano PM, Lowe LP, Metzger BE; HAPO Follow-up Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes and Childhood Glucose Metabolism. Diabetes Care. 2019 Jan 17. pii: dc181646. doi: 10.2337/dc18-1646. 埼玉医科大学　総合医療センター　内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田　昌文　 Matsuda, Masafumi 2019年1月24日　8:30-8:55 ８階　医局

2. http://www.hapo.northwestern.edu/ https://youtu.be/EZFXr6y4f6o

3. Publications Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-up Study Lowe WL, Scholtens DM, Lowe LP, et al (2018). Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism and Childhood Adiposity. JAMA, 320(10). Full article Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study 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 (2008). Hyperglycemia and adverse pregnancy outcomes. New England Journal of Medicine, 358(19). Abstract | Full article | Appendix

4. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Original ArticleHyperglycemia and Adverse Pregnancy Outcomes The HAPO Study Cooperative Research Group Boyd E. Metzger, M.D., Lynn P. Lowe, Ph.D., Alan R. Dyer, Ph.D., Northwestern University Feinberg School of Medicine, Chicago; Elisabeth R. Trimble, M.D., Queen’s University Belfast, Belfast, Northern Ireland; Udom Chaovarindr, M.D., Rajavithi Hospital, Bangkok, Thailand; Donald R. Coustan, M.D., Women and Infants’ Hospital of Rhode Island–Brown University Medical School, Providence, RI; David R. Hadden, M.D., David R. McCance, M.D., Royal Jubilee Maternity Hospital, Belfast, Northern Ireland; Moshe Hod, M.D., Helen Schneider Hospital for Women, Rabin Medical Center–Sackler Faculty of Medicine, Tel-Aviv University, Petah- Tiqva, Israel; Harold David McIntyre, M.B., B.S., Jeremy J.N. Oats, M.D., Mater Misericordiae Mothers’ Hospital–University of Queensland, Brisbane, Australia; Bengt Persson, M.D., Ph.D., Karolinska Institute, Stockholm, Sweden; Michael S. Rogers, M.D., Prince of Wales Hospital–Chinese University of Hong Kong, Hong Kong; and David A. Sacks, M.D., Kaiser Foundation Hospital, Bellflower, CA N Engl J Med Volume 358(19):1991-2002 May 8, 2008

5. The group developed diagnosticcut points for the fasting, 1-h, and 2-h plasma glucose measurements that conveyed an odds ratio for adverse outcomes of at least 1.75 compared with women with the mean glucose levels in the HAPO study(23316 pregnant women). 平均血糖 (FPG 80.9mg/dl, 1-h PG 134.1mg/dl, 2-h PG 111.0mg/dl) の女性に比較し1.75倍以上のリスクとなる血糖が閾値

6. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Follow-up Study Lowe WL, Scholtens DM, Lowe LP, et al (2018). Association of Gestational Diabetes With Maternal Disorders of Glucose Metabolism and Childhood Adiposity. JAMA, 320(10).

7. 1 Northwestern University Feinberg School of Medicine, Chicago, IL 2 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 3 Kaiser Permanente Southern California, Pasadena, CA 4 Schneider Children’s Medical Center of Israel, Petah Tiqva, Israel and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 5 Royal Victoria Hospital, Belfast, U.K. 6 The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada 7 Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 8 Royal Manchester Children’s Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Healthy Sciences Centre/School of Medical Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, U.K. 9 The Chinese University of Hong Kong/Prince of Wales Hospital, Hong Kong, China 10MetroHealth Medical Center/Case Western Reserve University, Cleveland, OH Diabetes Care. 2019 Jan 17. pii: dc181646. doi: 10.2337/dc18-1646.

8. OBJECTIVE Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.

9. RESEARCH DESIGN AND METHODS HAPO Follow-up Study (FUS) included 4,160 children ages 10–14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index.

17. RESULTS For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78–1.52) for IFG and 1.96 (1.41–2.73) for IGT. GDM was positively associated with child’s 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference −76.3 [95% CI −130.3 to −22.4] and −0.12 [−0.17 to −0.064]), respectively, but not insulinogenic index.

18. CONCLUSIONS Offspring exposed to untreated GDM in utero are insulin resistant with limited β-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT.

19. Message HAPO研究の経過をみている報告 GDMの子供もインスリン抵抗性がありインスリン分泌もdisposition indexでみると低下している。 今後、糖尿病発症について母も子も報告がされてくると思われるがかなり先になりそう。