Children of mothers with untreated gestational diabetes mellitus are at risk of insulin resistance and impairment in glucose metabolism.
Intrauterine exposure to maternal preexisting diabetes or gestational diabetes mellitus is associated with a higher risk for offspring abnormal glucose metabolism.
Previous studies focused on women with a high prevalence of diabetes, making it unclear whether these results could be extrapolated to other populations. More recently, maternal treatment during pregnancy has confounded studies examining the impact of the intrauterine environment on offspring risk of hyperglycemia. Studies have also not adequately addressed whether hyperglycemia in utero less than overt diabetes is associated with altered glucose metabolism in childhood.
A new study has examined associations of gestational diabetes mellitus not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort.
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 approximately 28 weeks of gestation with blinded glucose values. The primary predictor was gestational diabetes mellitus 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.
It was found that 10.6% of children from mothers with gestational diabetes had impaired glucose tolerance compared with 5.0% of children of mothers without gestational diabetes. Impaired fasting glucose frequencies were 9.2% and 7.4%, respectively. Gestational diabetes 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 respectively, but not insulinogenic index.
The study concluded that maternal hyperglycemia during pregnancy is associated with a higher risk of impaired glucose tolerance in childhood. In addition, this association is evident even when maternal gestational diabetes is defined by the less stringent criteria. This association persisted after adjustment for maternal BMI and childhood adiposity, which are also associated with gestational diabetes in this cohort.
In another recent meta-analysis, there was an investigation of the association of maternal hyperglycemia exposure during pregnancy (gestational diabetes mellitus, type 1 diabetes mellitus (T1DM) and T2DM) with obesity and abnormal glucose tolerance in offspring, and the age at occurrence.
Twenty observational studies were included involving a total of 26,509 children. Offspring of gestational diabetes mothers had higher BMI z-score in childhood. Offspring of mothers who have T1DM had higher BMI z-score from prepubertal to adolescent compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of mothers who have gestational diabetes. Offspring of mothers who have gestational diabetes had higher 2-hour plasma glucose from prepubertal to early adulthood, while those of T1DM mothers had higher rate of T2DM in 2-5 year olds to early adulthood compared with control. As there was only one study with offspring of mothers who have T2DM evidence is sparse.
The study concluded that exposure to maternal hyperglycemia was associated with obesity of the offspring and abnormal glucose tolerance, especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only.
Both studies showed no association between gestational diabetes and child fasting glucose levels, but there was an association between gestational diabetes and impaired glucose tolerance.
- Maternal hyperglycemia during pregnancy is associated with a higher risk of impaired glucose tolerance in childhood.
- There was no association between gestational diabetes and child fasting glucose levels in recent studies.
- Well-powered interventional trials are needed to address the impact of prevention and treatment of gestational diabetes on subsequent childhood glucose outcomes.
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 Mellitus and Childhood Glucose Metabolism. Diabetes Care. 2019 Mar;42(3):372-380.
Kawasaki M, Arata N, Miyazaki C, Mori R, Kikuchi T, Ogawa Y, Ota E. Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A systematic review and meta-analysis. PLoS One. 2018 Jan 12;13(1):e0190676.
Dahlia Elimairi, Pharm D Student UC Denver Skaggs School of Pharmacy