Sex-Differences in the Metabolic Health of Offspring of Parents with Diabetes: A Record-Linkage Study

Abstract

Maternal diabetes in pregnancy affects offspring health. The impact of parental diabetes on offspring health is unclear. We investigated the impact of parental diabetes on the metabolic-health of adult-offspring who did not themselves have diabetes. Data from the Generation Scotland: Scottish Family Health Study, a population-based family cohort, were record-linked to subjects' own diabetes medical records. From F0-parents, we identified F1-offspring of: mothers with diabetes (OMD, n = 409), fathers with diabetes (OFD, n = 468), no parent with diabetes (ONoPD, n = 2489). Metabolic syndrome, body, biochemical measurements and blood-pressures were compared between F1-offspring groups by sex. A higher proportion of female OMD had metabolic syndrome than female OFD or ONoPD (P<0.0001). In female offspring, predictors of metabolic syndrome were: having a mother with diabetes (OR = 1.78, CI 1.03-3.07, [reference ONoPD]), body mass index (BMI, OR = 1.21, CI 1.13-1.30) and age (OR = 1.03, CI 1.01-1.06). In male offspring, predictors of metabolic syndrome were: BMI (OR = 1.18, CI 1.09-1.29) and percent body-fat (OR = 1.12, CI 1.05-1.19). In both sexes, OMD had higher blood-pressures than OFD (P<0.0001). In females, OMD had higher glucose (P<0.0001) and percent body-fat (P<0.0001) compared with OFD or ONoPD. OMD and OFD both had increased waist-measurements (P<0.0001), BMI (P<0.0001) and percent body-fat (P<0.0001) compared with ONoPD. Female OMD and OFD had lower HDL-cholesterol levels (P<0.0001) than female ONoPD. Parental diabetes is associated with higher offspring-BMI and body-fat. In female offspring, maternal diabetes increased the odds of metabolic syndrome, even after adjusting for BMI. Further investigations are required to determine the mechanisms involved.

Fig 1. Summary of the linkage process and identification of the F₁-offspring and F₂-grandchildren groups for analysis.

Linkage process of GS:SFHS data. Subjects who had children or parents within the GS:SFHS cohort and had health numbers were sent via HIC to ISD for linkage to their own diabetes and birth medical records. From the diabetes-linked data, the F₁-offspring of the F₀-parents with or without diabetes were identified. F₁-offspring who had children of their own were separated for analysis of the effects of grandparental diabetes on F₂-grandchildren. F₁-offspring groups were defined by whether their mother (OMD) or father (OFD) or no parent had diabetes (ONoPD). F₂-grandchildren groups with grandparents with diabetes were grouped by maternal or paternal lineage: grandchild of maternal grandmother with diabetes (GMGMD), grandchild of maternal grandfather with diabetes (GMGFD), grandchild of paternal grandmother with diabetes (GPGMD), grandchild of paternal grandfather with diabetes (GPGFD), or grandchild of grandparents with no diabetes (GNoGPD). * Mothers who developed GDM during pregnancy were identified from SMR02

Fig 2. Body measurements, blood biochemistry and blood pressure measurements in offspring by parental group.

Box-and-whiskers plots show median and IQR (‘+’ within the box denotes mean value) for the OMD (white boxes), OFD (hatched boxes) and ONoPD (grey boxes) in males (left) and females (right); box-and whiskers for rest of cohort (RoC, i.e. all those without diabetes excluded from the F₁-offspring groups, [black boxes] for males and females) are also shown for comparison. Graphs are shown for Waist (A), HDL-cholesterol (B), Glucose (C), Systolic-blood pressure (D), Diastolic-blood pressure (E), BMI (F) and Percent body-fat (G). Groups were compared by Kruskal-Wallis, with level of significance between the groups indicated (* P<0.05, **P<0.01, *** P<0.001, **** P<0.0001).