Recent increases in childhood diabetes present an urgent public health challenge: to mount effective primary and secondary prevention efforts as soon as possible. We must therefore understand the mechanisms underlying the current epidemic, particularly the interaction of genetics with the changing epidemiology of behavioral risk factors. We propose to investigate the determinants of childhood diabetes risk in affected probands and their family members. This is a competing continuation application for the population-based Chicago Childhood Diabetes Registry. This database represents the largest number of non-Hispanic black children with diabetes worldwide, and the largest patient database for Latino children in the continental US. Ongoing ascertainment of incident cases will provide basic epidemiologic data and will anchor a further effort, in families of affected children, to describe the spectrum of youth-onset glucose intolerance in terms of inheritance and the expression of disease susceptibility alleles within families. We will specifically address these hypotheses: 1. That diabetes in youth is caused by a spectrum of etiologic processes, from the insulinopenia of autoimmune type 1 to obesity-related, insulin-resistant type 2 diabetes. A subset of children demonstrate a mixed etiology, with autoimmune beta-cell destruction aggravated by the presence of insulin resistance due to genetic susceptibility, obesity and/or physical inactivity. 2. That secular changes in the epidemiology of childhood diabetes are directly related to changes in the prevalence of both type 1 and type 2 risk factors, including obesity, physical inactivity, and perinatal exposures. 3. That familial aggregation of specific traits affects the risk of chronic complications in young people with diabetes, over and above that of glycemic control. Ultimately, this approach will permit a truly population-based molecular epidemiologic study of early-onset diabetes in families from a range of ethnic groups.
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