In non-transplant patients with Type II diabetes, insulin resistance and hyperinsulinemia are associated with specific dyslipidemias that correlate with risk for atherosclerotic cardiovascular disease (ASCVD). In contrast, dyslipidemias in liver transplant (LT) recipients are poorly characterized their link to insulin resistance and hyperinsulinemia is undefined, and their underlying causative mechanisms are unstudied. Characterization of dyslipidemias in LT patients and definition of pathogenesis are essential for development of effective therapeutic strategies. The long-term objective of these studies is to characterize the lipid and lipoprotein disorders in LT recipients and discern related mechanisms. To enroll in this study, subjects must be adults having received a liver transplant greater than 6 months ago. Subject's liver function must be stable, as determined by their doctors, and their treatment must be cyclosporine or tacrolimus, no glucocorticoids or other immunosuppressive agents.
The Specific Aims are defined according to the following working hypothesis: Individual variation in post-LT dyslipidemias are due to differences in the metabolic response to immunosuppression, donor hepatic, and recipient extrahepatic lipid and lipoprotein metabolism. As a result the following testable hypotheses are: 1) LDL cholesterol will be higher in patients on CSA compared to those on TAC; 2) ApoE4 phenotype is associated with the highest tertile of LDL cholesterol; 3) depressed bile acid synthesis is associated with elevated LDL cholesterol, and 4) insulin resistance will be found in patients with elevated triglyceride or VLDL levels. Subjects taking part in this research will have a medical history and examination, including routine blood laboratory tests. Based on the lipid tests, they may be asked to participate in additional tests called Liver Metabolic Studies or Insulin Sensitivity Studies.
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