Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism
Authors: William L. Lowe, Denise M. Scholtens, Alan Kuang, Barbara Linder, Jean M. Lawrence, Yael Lebenthal, David McCance, Jill Hamilton, Michael Nodzenski, Octavious Talbot, Wendy J. Brickman, Peter Clayton, Ronald C. Ma, Wing Hung Tam, Alan R. Dyer, Patrick M. Catalano, Lynn P. Lowe, Boyd E. Metzger, Chaicharn Deerochanawong, Thadchanan Tanaphonpoonsuk, Sukeeta Binratkaew Uraiwan Chotigeat, Wanee Manyam, Martinette Forde, Andre Greenidge, Kathleen Neblett, Paula Michele Lashley, Desiree Walcott, Katie Corry, Loraine Francis, Jo-anne Irwin, Anne Langan, David R. McCance, Maureen Mousavi, Ian Young, Jennifer Gutierrez, Jennifer Jimenez, Jean M. Lawrence, David A. Sacks, Harpreet S. Takhar, Elizabeth Tanton, Wendy J. Brickman, Jennifer Howard, Jami L. Josefson, Lauren Miller, Jacqui Bjaloncik, Patrick M. Catalano, Ajuah Davis, Michaela Koontz, Larraine Presley, Shoi Smith, Amanda Tyhulski, Albert Martin Li, Ronald C. Ma, Risa Ozaki, Wing Hung Tam, Michelle Wong, Cindy Siu Man Yuen, Peter E. Clayton, Aysha Khan, Avni Vyas, Michael Maresh, Hadasse Benzaquen, Naama Glickman, Alona Hamou, Orna Hermon, Orit Horesh, Yael Keren, Yael Lebenthal, Shlomit Shalitin, Kristina Cordeiro, Jill Hamilton, Hahn Y. Nguyen, Shawna Steele, Fei Chen, Alan R. Dyer, Wenyu Huang, Alan Kuang, Maria Jimenez, Lynn P. Lowe, William L. Lowe, Boyd E. Metzger, Michael Nodzenski, Anna Reisetter, Denise Scholtens, Octavious Talbot, Paul Yim, David Dunger, Alicia Thomas, Mary Horlick, Barbara Linder, Aynur Unalp-Arida, Gilman Grave
Journal: Diabetes Care (2019)

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. 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 of 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. 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. 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.