Risk of diabetes among related and unrelated family members

Aims: The aim was to explore familial aggregation of diabetes in genetically related and unrelated individuals. Methods: We included citizens from Danish nationwide registries between 1995 and 2018 and calculated rate ratios (RR) of diabetes based on family relation using Poisson regression. Results: Of 7.3 million individuals eligible for inclusion, we identified 343,237 (4.7%) with diabetes. The RR of diabetes was 2.02 (95% CI: 1.99-2.05; p < 0.0001) if any relative had diabetes, 1.79 (95% CI: 1.76-1.83) if a father had diabetes, and 2.06 (95% CI: 2.02-2.10) if a mother had diabetes. If both parents had diabetes, the RR was 3.40 (95% CI: 3.24-3.56). Among full siblings, the RR for developing diabetes was 2.77 (95% CI: 2.71-2.84) and 5.76 (95% CI: 5.00-6.63) for twins. For second-degree relatives, half siblings with a common mother had a RR of 2.35 (95% CI: 2.15-2.56), and with a common father 1.99 (95% CI: 1.81-2.17). Furthermore, the RR was 1.60 (95% CI: 1.56-1.64) if a wife had diabetes, and 1.41 (95% CI: 1.38-1.44) if a husband had diabetes. A subgroup analysis of individuals receiving insulin only treatment (N = 23,054) demonstrated a similar risk pattern, although with slightly higher risk estimates. Conclusions/interpretation: Family aggregation of diabetes is associated with genetic disposition with maternal status being the predominant factor. Furthermore, we observed increased risk of diabetes in second-degree relatives, and between unrelated spouses, indicating that environmental factors influence diabetes risk substantially. (C) 2020 Elsevier B.V. All rights reserved.