The DCCT, a multicenter randomized controlled clinical trial in 1,441 patients with IDDM, demonstrated beneficial effects of intensive diabetes therapy including delay of onset of retinopathy, nephropathy and neuropathy in intensively treated patients. However, in a subset of patients, intensive therapy was associated with greater than 14 kg weight gain. The dyslipidemia seen in these patients, along with other phenotypic changes, suggests the insulin resistance syndrome seen in non-diabetic, centrally obese individuals. These subjects are now being followed to study the natural history of the development of nephropathy and atherosclerosis in IDDM. It is hypothesized that weight gain with intensive therapy reflects genetic susceptibility for the central obesity/insulin resistance syndrome. The Seattle cohort (n=80) of the DCCT/EDIC study wil be evaluated for body composition, insulin sensitivity and dyslipidemia, as will their first degree relatives. It is expected that those individuals who gained excess weight with intensive diabetes therapy are centrally obese, insulin resistant, have small, dense LDL and come from obese families.
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