Maternal and umbilical cord serum lipids in gestational diabetes predict offspring insulin secretion and resistance at the age of nine years

TL;DR

Pregnancy lipid levels in mothers with gestational diabetes may influence their child's insulin function at age nine.

Contribution

The study identifies cord serum lipid profiles linked to childhood insulin resistance and β-cell function.

Findings

Higher cord serum docosahexaenoic acid and linoleic acid were associated with lower β-cell function in children.

Linoleic acid was inversely related to insulin resistance in children whose mothers received insulin treatment.

Maternal lipid associations were not significant after adjustment for multiple comparisons.

Abstract

Maternal metabolism in pregnancy is a major determinant of intrauterine milieu and is assumed to have long-term consequences in the offspring.

To study whether maternal or cord serum lipids are related to measures of insulin resistance and β-cell function in childhood.

This is a secondary analysis of a previous trial in which women with newly diagnosed gestational diabetes were randomized to metformin versus insulin treatment. Maternal serum lipids were measured during pregnancy and umbilical cord serum lipids at delivery. Offspring insulin resistance and β-cell function were assessed at nine years of age using serum insulin, C-peptide, and glucose concentrations measured during an oral glucose tolerance test. A total of 122 mother-child dyads were included in the analyses.

After adjusting for multiple comparisons, higher cord serum docosahexaenoic acid, linoleic acid, and the ratio of linoleic acid to total fatty acids were significantly related to lower indices of β-cell function in childhood. In interaction models, cord serum linoleic acid was inversely related to offspring HOMA2-IR and measures of β-cell function only in the participants treated with insulin in pregnancy. Associations between maternal lipids and outcomes were not significant after Bonferroni adjustment.

Cord serum lipids, and potentially maternal lipids, are related to childhood insulin function. These findings highlight the importance of maternal lipid metabolism in pregnancies affected by gestational diabetes. Given the observed differences between metformin and insulin treatment groups, the feto-placental effects of prenatal metformin exposure should be further investigated.

NCT02417090 at ClinicalTrials.gov, registered April 14th 2015.

This is secondary analysis of a previous study registered at ClinicalTrialg.gov (NCT02417090) on April 14th 2015.

The online version contains supplementary material available at 10.1007/s11306-025-02281-9.

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