This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This project started as an ancillary study of lipoprotein metabolism to the NIH sponsored clinical trial of intensive diabetes therapy in type 1 diabetes to prevent microvascular disease called the Diabetes Control and Complication Trial (DCCT). The Epidemiology of Diabetes Intervention and Complications (EDIC) is a ten year non-interventional follow-up of the DCCT cohort to evaluate the natural history of macrovascular and nephropathic complications in type 1 diabetes. In the DCCT, we found that atherogenic small dense LDL was increased as a result of intensive diabetes therapy in those who gained weight. Those who gained weight with intensive diabetes therapy were centrally obese, insulin resistant, hypertensive, dyslipidemic and had type 2 diabetic parents. This suggests that they had inherited the genes for the metabolic-central obesity syndrome in addition to type 1 diabetes. This proposal will use the phenotypes of 1) excessive weight gain with intensive diabetes therapy and 2) the presence of small dense LDL particles as markers of the central obesity - insulin resistance metabolic syndrome that occurred in this subset of type 1 subjects during intensive diabetes therapy. Intraabdominal fat by CT scan and postheparin plasma hepatic lipase will be measured to further develop the phenotype associated with the excessive weight gain with intensive therapy and with development of nephropathy in the Seattle cohort and the three Minnesota cohorts of EDIC.
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