Familial risk factors for microvascular complications and differential male-female risk in a large cohort of American families with type 1 diabetes.

CONTEXT

Type 1 diabetes (T1D) complications are responsible for much of the disease morbidity. Evidence suggests that familial factors exert an influence on susceptibility to complications.

OBJECTIVES

We investigated familial risk factors and gender differences for retinopathy, nephropathy, and neuropathy.

DESIGN AND SETTING

This study was a case-control design nested on a cohort of T1D families. We collected data (questionnaire, medical records) starting in 1988. Follow-up has been ongoing since 2004.

PATIENTS

There were 8114 T1D patients among 6707 families. All patients had T1D onset age younger than 30 yr and required insulin treatment. Patients who remained without a complication after more than 15 yr of diabetes were considered to be without that complication for our analyses.

RESULTS

A complication in a sibling increased the risk for that complication among probands: odds ratio 9.9 (P < 0.001) for retinopathy, 6.2 for nephropathy (P < 0.001), and 2.2 for neuropathy (P < 0.05). Compared with male probands, a female T1D proband had 1.7-fold higher retinopathy risk (P < 0.001) and 2-fold higher neuropathy risk (P < 0.001). T1D cases with onset between ages 5 and 14 yr had an increased complications risk compared with subjects diagnosed either at a very young age or after puberty. The presence of one complication significantly increased the risk for others. If a parent had type 2 diabetes, the risk for nephropathy increased (odds ratio 1.9, P < 0.01, but T1D in a parent did not increase the risk).

CONCLUSIONS

We confirmed that familial factors influence T1D microvascular pathologies, suggesting a shared genetic basis for complications, perhaps independent of T1D susceptibility. We also found an unexpected increased female risk for complications.