Research Article|Articles in Press, 110633

Low-density lipoprotein cholesterol levels are associated with first-phase insulin release



      Prior studies provided evidence that low-density lipoprotein (LDL)-cholesterol-lowering statins reduce cardiovascular events while conveying an increased risk of type 2 diabetes. The aim of this study was to investigate the association between LDL levels and both insulin sensitivity and insulin secretion in a cohort of 356 adult first-degree relatives of patients with type 2 diabetes.


      Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp and first-phase insulin secretion was measured by both intravenous glucose tolerance test (IVGTT) and OGTT.


      LDL-cholesterol levels were not independently associated with insulin-stimulated glucose disposal. After adjusting for several potential confounders, LDL-cholesterol concentration exhibited a positive independent association with acute insulin response (AIR) during IVGTT and with the OGTT derived Stumvoll first-phase insulin secretion index. When insulin release was adjusted for the underlying degree of insulin sensitivity, using the disposition index (AIR x insulin-stimulated glucose disposal), β-cell function was significantly associated with LDL-cholesterol levels, even after further adjusting for several potential confounders.


      The present results suggest that LDL cholesterol is a positive modulator of insulin secretion. The deterioration in glycemic control observed during treatment with statins might thus be explained by an impairment in insulin secretion due to the cholesterol-lowering effect of statins.


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