Progression of Cardiovascular Disease in TID: CADRE/EDC

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DESCRIPTION (provided by applicant): Although the prognosis in patients with Type 1 diabetes (T1D) has improved considerably over the last 50 years, the morbidity and mortality rates still greatly exceed that of the general population. Research has demonstrated that people with T1 D have a ten fold or greater increase in cardiovascular risk, particularly from coronary artery disease (CAD). CAD in TID, as in the general population, is likely to result from an amalgam of different factors. A variety of studies in the United States and Europe have yielded some important clues as to the potential causes of CAD in TID. One of the major underlying features we feel is insulin resistance (IR). It is proposed that IR underlies both CAD and renal disease in T1D and provides a "common soil" which is responsible for much of the link between renal disease and CAD. The Epidemiology of Diabetes Complications Study (EDC) has examined the prevalence, incidence, and risk factors contributing to diabetes complications for over 16 years. The study population is a well-defined cohort of TID patients identified from the Children's Hospital of Pittsburgh registry. All 658 examined subjects at baseline (1986-1988) were diagnosed between 1950-80 at age <17 years. During the proposed project period, we plan to study the interrelationships between renal disease, IR and CAD in the context of various degrees of renal disease as a substudy of EDC. More specifically we aim to: characterize and compare insulin resistance factors of those with and without clinical CAD, within and across strata of renal disease (i.e. normal, micro, and macroalbuminuria); determine if accounting for estimated insulin resistance (estimated glucose disposal rate, eGDR) and/or IR related factors will explain the excess CAD in renal disease; determine if IR, as represented by positron emission tomography (PET) determined skeletal muscle glucose uptake, differs significantly in those with and without CAD both, in the absence of renal disease and in the presence of nephropathy; and to determine if total sitosterol concentration is increased in those with CAD compared to those without CAD. We also plan to conduct further statistical analyses of CAD risk factors that may mediate the renal- CAD diabetes complications risk, including asymmetric dimethylarginine (ADMA) and Nuclear Magnetic Resonance (NMR) lipoprotein profile, using the follow up data set that will become available during this study period. This study will help advance our knowledge of CAD in T1D and hopefully lead to appropriate preventative strategies.