Adriëtte Oostvogels

122 Chapter 5 Abstract Aim: To investigate whether children with family history of diabetes (FHD) in second-degree relatives (grandparents, aunts/uncles) are at increased risk of developing obesity and diabetes, and whether this risk differs between transmission through the maternal or paternal line. Methods: In the multi-ethnic population-based cohort ABCD-study we compared body mass index (BMI), waist-to-height-ratio (WHtR), fat percentage (fat%), fasting glucose, and C-peptide in 5-6 year old children without second-degree FHD (n=2226), to children with maternal only (n=353), paternal only (n=281) or both maternal and paternal (n=164) second-degree FHD. Children of diabetic mothers or fathers were excluded. Results: Children with no, maternal, paternal or both maternal and paternal second-degree FHD did not differ in body composition after adjustments for maternal, paternal and childhood covariates. However, children with both maternal and paternal second-degree FHD had increased C-peptide (0.03 nmol, 95%CI: 0.01-0.05) compared to children with no, maternal or paternal family history of diabetes. Results were similar when analyses were restricted to only Dutch children. Conclusion: Children with FHD in second-degree relatives on both the maternal and paternal side have higher C-peptide levels already at early age. This might be the result of a double burden of a shared obesogenic lifestyle, or of more diverse diabetogenic genes compared to children without FHD or with only one grandparent, uncle or aunt with diabetes. Second-degree FHD could be used as screening tool in public health to identify children at risk of adverse metabolic outcomes and a possible future disease risk.