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Randomized Controlled Trial
. 2025 Jun 22;21(4):87.
doi: 10.1007/s11306-025-02281-9.

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

Mikael Huhtala  1   2 , Tapani Rönnemaa  3   4 , Kristiina Tertti  5   6 , Harri Niinikoski  7 , Elisa Paavilainen  7
Affiliations
Randomized Controlled Trial

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

Mikael Huhtala et al. Metabolomics. .

Abstract

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

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

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration number: NCT02417090 at ClinicalTrials.gov, registered April 14th 2015.

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

Keywords: Gestational diabetes; Insulin resistance; Insulin secretion; Lipidomics; Metabolomics; Metformin.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study was approved by the ethics committee of the Hospital District of Southwest Finland (ETMK 31/2015) on April 27, 2015, and the study participants, signed an informed consent. The researchers informed mothers who discussed with their children about the study. The children also read the age-appropriate research bulletin and signed their own consent. Software availability: All analyses were carried out using readily available open-source software.

Figures

Fig. 1
Fig. 1
Study flowchart. T1DM: type 1 diabetes, NMR: nuclear magnetic resonance (spectroscopy)
Fig. 2
Fig. 2
Associations between metabolites and outcome variables. Only those metabolites are included which have at least one significant (p < 0.01) association. Adjusted model is adjusted for pBMI. In the cord serum lipoprotein lipids were log-converted (#). ns: non-significant (p-value ≥ 0.01). HDL: high-density lipoprotein, IDL: intermediate-density lipoprotein, FA: fatty acids
Fig. 3
Fig. 3
The effects of GDM treatment in pregnancy on associations between metabolites and outcome variables. Only those metabolites are included which have at least one significant (p < 0.01) association in any subgroup and significant interaction (interaction term pp 0.01) in at least one of the associations. Adjusted model. Significant interaction terms are noted with an asterisk (*). Cord serum lipoprotein lipids were log-transformed (#). ns: non-significant (p-value ≥ 0.01). HDL: high-density lipoprotein, LDL: low-density lipoprotein, FA: fatty acids, MUFA: monounsaturated FA, SFA: saturated FA
See this image and copyright information in PMC

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