Fluvastatin Improves Insulin Resistance in Nondiabetic Dyslpidemic Patients

Abstract

Statins have multiple actions, independent of their classical effects on lipoproteins. The data about the effects of statins on insulin resistance is controversial. This study was designed to search the statin effects on nondiabetic dyslipidemic patients. Thirty-five (17 male, 18 female) consecutive dyslipidemic patients 54.25 +/- 8.81 yr were enrolled in the study. After a standard follow-up period of lifestyle modification, the patients were given fluvastatin 40 mg/d for 8 wk. Serum analyses were done both before and after treatment. Insulin resistance was assessed by homeostasis assessment model (HOMA). Fasting plasma triglyceride, total and LDL cholesterol, fasting insulin, and HOMA index were significantly reduced and HDL cholesterol was improved after fluvastatin treatment. HOMA-IR was not correlated with triglycerides, LDL, HDL, or total cholesterol levels. The same situation was present for both fasting plasma insulin and fasting plasma glucose levels. Also age was not associated with HOMA-IR and fasting plasma insulin levels. As a conclusion, the present study indicates that fluvastatin treatment improves insulin resistance in dyslipidemic patients who do not have diabetes or impaired fasting glucose. Also, the effect of fluvastatin on insulin resistance is not associated with the lowering of triglycerides. The latter finding indicates that the effect of statins on insulin sensitivity may not be related with the lowering of triglycerides in dyslipidemic patients.

Effects of fluvastatin on insulin resistance and cardiac morphology in hypertensive patients

“…That factor, together with the short 3-month study period of Sari et al, might explain why that study detected no improvement in HOMA-IR. As in our study, Sonmez et al 33 reported an improvement in insulin resistance in 35 hypercholesterolaemic patients treated with fluvastatin. We also found that there was no correlation between changes in patient lipid profile and the observed improvement in insulin resistance, suggesting potential fluvastatin pleiotropism.…”

Comparative effects of pitavastatin and probucol on oxidative stress, Cu/Zn superoxide dismutase, PPAR-γ, and aortic stiffness in hypercholesterolemia

“…Recent clinical trials demonstrated that PPAR-␣ or PPAR-␥ agonist improved the outcome of atherosclerotic heart disease (10,14), whereas dual-PPAR agonist did not (34). In addition, statins improved insulin resistance (41) and antioxidant activities, including the restoration of Cu/ZnSOD activity (48), prevented the development of diabetes, reduced lipid levels (13,38), and improved clinical outcome in patients with hypercholesterolemia (1). These results, taken together with those of the present study, indicate that pitavastatin may selectively activate PPAR-␥ and Cu/ ZnSOD in hypercholesterolemia as pleiotropic effects.…”

“…These "pleiotropic effects" of statins include improvement of endothelial function, antithrombotic actions, plaque stabilization, reduction of the vascular inflammatory process, and an antioxidant function through the inhibition of NAD(P)H oxidase or the increase in SOD activity (3,6,26,32). Statins are also reported to improve insulin resistance (41) and antioxidant properties, including the restoration of Cu/ZnSOD activity (48), and prevent the development of diabetes in patients with hypercholesterolemia (13,38). Taken together, these observations allow one to assume that statins may have antiatherogenic actions through PPAR and Cu/ZnSOD activation, in addition to antidyslipidemic actions.…”

Reduced Incidence of New-Onset Diabetes Mellitus after Renal Transplantation with 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitors (Statins)

“…In addition, statins have several pleiotropic effects unrelated to lipid levels including reduced inflammation, improved endothelial function (14) and improved insulin sensitivity (15). Statins may improve insulin resistance even in nondiabetic patients (16), and may actually have a protective effect against the development of diabetes in the general population (17). We therefore hypothesized that statins would demonstrate a protective effect against new-onset diabetes in renal transplant recipients (RTR), whose risk factors for diabetes are well defined (2,10) and somewhat different (6)(7)(8)(9).…”