PracticeUpdate Diabetes March 2019

EDITOR’S PICKS 16

Maternal Glycemia and Childhood Glucose Metabolism Diabetes Care Take-home message • The authors performed an observational study to determine the relationship between maternal glycemia in pregnancy and glucose outcomes in the offspring during childhood. This study followed 4160 children. Maternal fasting plasma glu- cose levels were associated with offspring fasting glucose and HbA1c. An inverse relationship was observed between maternal fasting plasma glucose and insulin sensitivity. These observations were not influenced by maternal or child BMI. • The results indicate that maternal glucose influences both glucose outcomes and insulin resistance in children.

COMMENT By Christina S. Han MD T he HAPO Follow-Up Study (HAPO FUS) expands our understand- ing of the long-term sequelae of in utero exposure to the spectrum of maternal diabetes. We have long understood that maternal pre-gesta- tional or gestational diabetes (GDM) can increase the risk of altered glu- cose metabolism in offspring, but the relationship across the spectrum of glu- cose categories, including those under the cutoff for GDM, had not previously been elucidated. " These findings further support the previous HAPO conclusions that GDM is not a dichotomous diagnosis… " The authors demonstrated a linear rela- tionship between pregnancy glucose levels and child glucose levels at 10 to 14 years of age, including for maternal levels below those diagnostic of GDM. Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1c, and inversely associated with insulin sensitivity. Maternal 1-h and 2-h plasma glucose (PG) was positively associated with child fasting, 30 min, 1-h/2-h PG, and A1c, and inversely associated with insulin sensitivity and disposition index. For impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), maternal FPG was asso- ciated with child IFG, and 1-h and 2-h PG with child IGT, with increased rates across increasing categories of mater- nal glucose. These associations were independent of maternal and child BMI. These findings further support the pre- vious HAPO conclusions that GDM is not a dichotomous diagnosis, and that offspring of pregnancies exhibit a continuum of sequelae from maternal hyperglycemia, which may persist into teenage years.

Abstract OBJECTIVE This study examined associations of maternal glycemia during pregnancy with child- hood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-Up Study included 4,832 children ages 10-14 whose mothers had a 75-g oral glucose tolerance test (OGTT) at ~ 28 weeks’ gestation. Of these, 4,160 children were evaluated for glu- cose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT. RESULTS Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity,

whereas 1-h and 2-h PG were inversely associ- ated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, fre- quencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insu- lin sensitivity and disposition index decreased. CONCLUSIONS Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glu- cose and insulin resistance independent of maternal and childhood BMI and family history of diabetes. Hyperglycemia and Adverse Pregnancy Out- come Follow-Up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabo- lism. Diabetes Care 2019 Jan 07;[EPub Ahead of Print], DM Scholtens, A Kuang, LP Lowe, et al.

Dr. Han is the UCLA MFM Fellowship Program Director of the Center for Fetal Medicine and Women’s Ultrasound in Los Angeles, California.

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