Familial Aggregation between the 14th and 21st Century and Type 2 Diabetes Risk in an Isolated Dutch Population

Introduction: The development of type 2 diabetes results from an interaction of hereditary factors and environmental factors. This study aimed to investigate the contribution of interrelatedness to the risk of developing type 2 diabetes in an isolated Dutch population. Materials and Methods: A genealogical database from inhabitants living on the former island Urk between the 14th and 21st century was constructed. In a case-control study, effects of interrelatedness and the risk of type 2 diabetes were estimated with Kinship Coefficients (KCs). Relative risks in first, second, and third degree relatives and spouses of inhabitants with type 2 diabetes were compared to matched controls. Results: Patients with type 2 diabetes were more interrelated, expressed by a higher KC compared to controls (7.2 vs. 5.2, p=0.001). First, second and third degree relatives had an increased risk of developing type 2 diabetes. Second degree relatives had a similar risk,1.7 (1.5-2.0) as third degree relatives,1.8 (1.5-2.2). Spouses of patients with diabetes had a 3.4 (2.7-4.4) higher risk of developing type 2 diabetes. Conclusions: Interrelatedness was higher among inhabitants with type 2 diabetes compared to controls. This differences extended beyond the nuclear family, thereby supporting the hypothesis that interrelatedness contributed to the development of type 2 diabetes on Urk. However, the size of this effect was small and the patterns of risk in first, second and third degree relatives suggested that factors other than interrelatedness were the main contributors to the development of type 2 diabetes on Urk.