We determined the magnitude of familial aggregation in the development of diabetic nephropathy (DN) among a population-based cohort of Finnish type 1 diabetic patients. Probands with type 1 diabetes were identified from the nationwide register of all Finnish cases diagnosed during [1965][1966][1967][1968][1969][1970][1971][1972][1973][1974][1975][1976][1977][1978][1979]. By 1998, there were 537 families with at least two siblings with type 1 diabetes. These 537 probands and their 616 diabetic siblings were followed for a diagnosis of DN until the end of 2001. We identified 323 cases of DN in these families. If the proband had DN, 38% of the siblings also had DN, whereas out of the diabetic siblings of the probands without DN, only 17% had DN (P ؍ 0.001). Diabetic siblings of the nephropathic probands had a 2.3 times (95% CI 1.4 -2.7) higher risk of DN compared with siblings of probands free of DN. The presence of a severe form of DN in the proband increases the risk threefold for diabetic siblings. Sex, the DN of the proband, the age at the onset of diabetes, and parental type 2 diabetes were significant predictors of DN among diabetic siblings. Although the majority of sibpairs with type 1 diabetes are discordant for DN, its presence in one sibling doubles the risk for the other diabetic siblings. Diabetes 53:2449 -2454, 2004 D iabetic nephropathy (DN) is a primary cause of excess mortality in type 1 diabetic patients (1). It affects about one-third of diabetic patients (2,3), increases the risk of cardiovascular diseases, and may lead to renal failure (1,4). The incidence of DN increases linearly during the first 20 years of the duration of diabetes, but starts to decline thereafter (2,3,5), suggesting that there may be a subset of diabetic patients at an especially high risk for DN. Not all patients with poor glycemic control develop DN during their lifetimes. The observed incidence patterns suggest that genetic factors linked to a predisposition for DN play an important role in the regulating processes that lead to DN.Familial clustering of DN has been previously reported (6 -8). Whether it is a consequence of shared environmental risk factors, genetic factors, or both is unclear. Thus far, no population-based studies on the familial clustering of DN have been published. Previous studies on DN within families have been based on small, hospital-based series. The aim of this study was to analyze the familial aggregation of DN in a large, Finnish, population-based cohort of type 1 diabetic patients and their siblings, avoiding the bias of a family ascertainment.
RESEARCH DESIGN AND METHODSWe identified families with two or more siblings with type 1 diabetes and followed the diagnoses of DN in the families until the end of 2001. The original cohort consisted of diabetic subjects diagnosed before the age of 18 years between 1965 and 1979 (n ϭ 5,126), who were included in the nationwide register of Finnish type 1 diabetic patients (9,10). This register was initially based on the Social Insurance Institution Cent...