Familiality of diabetes mellitus.

ABSTRACT

The aims of this study were to estimate relative risk for type 1 and type 2 diabetes in relatives of diabetic patients, and to test for excess relatedness among diabetic patients. Additionally, the difference in parental transmission of diabetes was investigated. This study used a unique Utah genealogical resource, linked to electronic medical records of the largest health provider in Utah. We identified 19,640 patients with a diagnosis of type 1 or type 2 diabetes. Relative Risks (RRs) for type 1 and type 2 diabetes were assessed for first-, second- and third-degree relatives of diabetic patients. The observed average relatedness of diabetic patients was compared to the expected relatedness using the Genealogical Index of Familiality (GIF). We observed significantly elevated RRs for type 1 diabetes in first-degree (RR=8.68; P<0.0001), second-degree (RR=1.93; P<0.0001) and third-degree relatives (RR=1.74; P<0.0001) of type 1 diabetic patients. RRs for type 2 diabetes were significantly increased in first-degree (RR=2.24; P<0.0001), second-degree (RR=1.36; P<0.0001) and third-degree relatives (RR=1.14; P<0.0001) of type 2 diabetic patients. Significantly increased RRs for type 1 diabetes were observed in the relatives of type 2 diabetic patients, and vice versa. The GIF analysis showed significant excess relatedness for type 1 diabetes cases, and independently for type 2 diabetes cases. Offspring of diabetic fathers were at significantly higher risk for type 1 diabetes than offspring of diabetic mothers (RR=9.73; P<0.0001 compared to RR=4.99; P<0.0001). No significant difference in parental transmission was observed for type 2 diabetes. Our results strongly support the existence of a genetic contribution to both type 1 and type 2 diabetes, and additionally suggest a relationship between both types of diabetes. Furthermore, our results suggest a significant difference in parental transmission of type 1 diabetes.