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