January 15, 2019
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Pregnancy glucose level affects childhood glucose, insulin resistance

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Higher levels of maternal glucose in utero are associated with higher levels of glucose and insulin resistance in childhood regardless of BMI and a family history of diabetes, according to findings published in Diabetes Care.

Denise M. Scholtens

“Glucose-related disorders, for example, impaired glucose tolerance, are evident not only for children of mothers with glucose levels high enough to be diagnosed as having gestational diabetes,” Denise M. Scholtens, PhD, chief of biostatistics in the department of preventive medicine at Northwestern University Feinberg School of Medicine, told Endocrine Today. “In fact, child glucose levels and risks of glucose-related disorders tend to steadily increase across the full range of maternal glucose during pregnancy.  Importantly, the relationship between maternal glucose and childhood glucose cannot be explained by childhood BMI or family history of diabetes.”

These findings were based on a follow-up study to the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort, which established an association between maternal glucose and perinatal outcomes. Scholtens and colleagues examined data from 4,160 mothers without diabetes and their children aged 10 to 14 years from 10 of the 15 field centers used in the original HAPO study. Participants were recruited from 2013 to 2016 and had a gestational age at delivery of at least 37 weeks.

Researchers recorded height, weight, fasting HbA1c and glucose and C-peptide levels at fasting, 1 hour and 2 hours. Participants also completed a 2-hour oral glucose tolerance test with a glucose load of 1.75 g/kg of body weight.

The researchers found that maternal fasting plasma glucose was positively associated with child FPG (beta = 0.046; 95% CI, 0.034-0.058) and HbA1c (beta = 0.013; 95% CI, 0.003-0.023), even when including adjustments for maternal and child BMI as well as a family history of diabetes. In fully adjusted models, maternal 1-hour plasma glucose was positively associated with child FPG (beta = 0.024; 95% CI, 0.013-0.036), child 30-minute plasma glucose (beta = 0.18; 95% CI, 0.13-0.22), child 1-hour plasma glucose (beta = 0.2; 95% CI, 0.15-0.26), child 2-hour plasma glucose (beta = 0.098; 95% CI, 0.061-0.14) and child HbA1c (beta = 0.018; 95% CI, 0.008-0.027). A positive association was also found for maternal 2-hour plasma glucose with child FPG (beta = 0.014; 95% CI, 0.0033-0.026), child 30-minute plasma glucose (beta = –43.6; 95% CI, –64.4 to –22.9), child 1-hour plasma glucose (beta = 0.15; 95% CI, 0.091-0.2), child 2-hour plasma glucose (beta = 0.059; 95% CI, 0.023-0.1) and child HbA1c (beta = 0.010; 95% CI, 0.0005-0.019).

In contrast, maternal fasting glucose (beta = –43.6; 95% CI, –64.4 to –22.9), maternal 1-hour plasma glucose (beta = –62.2; 95% CI, –82.4 to –42) and maternal 2-hour plasma glucose (beta = –41.5; 95% CI, –61.6 to –21.8) all were negatively associated with insulin sensitivity, based on Matsuda index, according to the researchers.

Additionally, maternal fasting glucose was associated with childhood impaired fasting glucose (beta = 1.22; 95% CI, 1.07-1.4) whereas maternal 1-hour plasma glucose (beta = 1.42; 95% CI, 1.23-1.63) and maternal 2-hour plasma glucose (beta = 1.17; 95% CI, 1.02-1.34) were associated with childhood impaired glucose tolerance.

“The earlier HAPO Study of mothers and their newborns demonstrated that high birthweight and other measures of newborn size were related to mothers’ glucose during pregnancy across the full range of glucose values,” Scholtens said. “It was surprising to confirm in the HAPO Follow-Up Study that maternal pregnancy glucose levels sustained a similar, graded relationship with glucose in these same children so many years later. It was also surprising to learn that the relationship did not simply reflect child adiposity, especially since we already know that maternal glucose is also related to that outcome.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.