Editors' ChoiceDiabetes

Transgenerational cycle of diabetes

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Science Translational Medicine  13 Feb 2019:
Vol. 11, Issue 479, eaaw5327
DOI: 10.1126/scitranslmed.aaw5327


Diabetes risk is shaped at birth.

The conditions encountered during fetal development can shape one’s long-term susceptibility to disease. This concept is referred to as the fetal origins of disease and may help explain the rising rates of type 2 diabetes (T2D) over the last few decades. Epidemiological studies have shown that children born to mothers who have diabetes during pregnancy are at high risk for diabetes later in life, leading to a greater number of women who develop diabetes during pregnancy and perpetuating the transgenerational transmission of diabetes from mothers to their offspring. The physiological mechanisms linking exposure to maternal diabetes during pregnancy to a child’s future risk for diabetes are not fully understood. However, a study by Lowe et al. provides insight into the effects of fetal exposure to gestational diabetes on critical physiological factors involved in the development of T2D.

The Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) follow-up study included 4160 children, ages 10 to 14 years, who were born to mothers with mild untreated gestational diabetes or normal glucose during pregnancy. Children completed oral glucose tolerance tests in which blood glucose and insulin concentrations were measured after fasting and at 30 min, 1 hour, and 2 hours after consuming a standardized glucose drink. The authors also assessed insulin sensitivity and β cell function in these children, adjusting for potential confounding child and maternal variables in the statistical analyses.

The study showed that 10.6% of children born to mothers with gestational diabetes compared with 5% of unexposed children had impaired glucose tolerance, but few children in either group had glucose concentrations high enough to meet the criteria for diabetes. Children exposed to gestational diabetes were also more insulin-resistant and had reduced β cell function, the primary defects in the pathogenesis of T2D. Interestingly, a subanalysis of younger children who had not yet started puberty revealed no group differences in these measures of glucose metabolism, suggesting that early childhood may be a critical window in development before the alterations in glucose metabolism begin to emerge. Future studies should define the biological mechanisms underlying the observed links between fetal exposure to gestational diabetes and altered glucose metabolism during childhood. This work could help identify therapeutic targets and windows of opportunity to prevent the development of T2D in high-risk children.

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