Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk—the PIOSTAT Study

OBJECTIVE -We hypothesized that simvastatin may reduce adiponectin levels and insulin sensitivity in hypercholesterolemic patients.RESEARCH DESIGN AND METHODS -This was a randomized, double-blind, placebo-controlled, parallel study. Age, sex, and BMI were matched. Thirty-two patients were given placebo, and 30, 32, 31, and 31 patients were given daily 10, 20, 40, and 80 mg simvastatin, respectively, during a 2-month treatment period.RESULTS -Simvastatin doses of 10, 20, 40, and 80 mg significantly reduced total cholesterol (mean changes 27, 25, 37, and 38%), LDL cholesterol (39, 38, 52, and 54%), and apolipoprotein B levels (24, 30, 36, and 42%) and improved flow-mediated dilation (FMD) (68, 40, 49, and 63%) after 2 months of therapy compared with baseline (P Ͻ 0.001 by paired t test) or compared with placebo (P Ͻ 0.001 by ANOVA). Simvastatin doses of 10, 20, 40, and 80 mg significantly decreased plasma adiponectin levels (4, 12, 5, and 10%) and insulin sensitivity (determined by the Quantitative Insulin-Sensitivity Check Index [QUICKI]) (5,8,6, and 6%) compared with baseline (P Ͻ 0.05 by paired t test) or compared with placebo (P ϭ 0.011 for adiponectin and P ϭ 0.034 for QUICKI by ANOVA). However, the magnitudes of these percent changes (FMD, adiponectin, and QUICKI) were not significantly different among four different doses of simvastatin despite dose-dependent changes in the reduction of apolipoprotein B levels.CONCLUSIONS -Simvastatin significantly improved endothelium-dependent dilation, but reduced adiponectin levels and insulin sensitivity in hypercholesterolemic patients independent of dose and the extent of apolipoprotein B reduction. Diabetes Care 31:776-782, 2008

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“…In our current study we evaluated 2 months of therapy. However, others using longer durations of therapy have found similar results (6,21,25).…”

Section: Effects On Lipidsmentioning

confidence: 68%

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

et al. 2008

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“…[26][27][28][29][30][31][32] Retinal vasculature is morphologically and functionally related to cerebral vessels because of their common origin from the internal carotid artery. An increased arterial retinal WLR has been described in patients with a history of cerebrovascular events.…”

Section: Discussionmentioning

confidence: 99%

Pilot Study for the Evaluation of Morphological and Functional Changes in Retinal Blood Flow in Patients with Insulin Resistance and/or Type 2 Diabetes Mellitus

Forst

Weber

Mitry³

et al. 2012

J Diabetes Sci Technol

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“…However, a recent study from Forst et al (2007) reported that simvastatin treatment resulted in Fig. 6 Liver tissue of standard diet (a) and high-fat diet rats (b, c).…”

Section: Discussionmentioning

confidence: 99%

“…Current treatment of non-alcoholic hepatic steatosis underlies weight loss (Comar and Sterling 2006;Federico et al 2006;Forst et al 2007;Mäuser et al 2007). Primary therapies act over lipids and glucose homeostasis in order to reduce insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia

Matafome

Nunes

Louro

et al. 2008

Naunyn-Schmied Arch Pharmacol

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Non-alcoholic fatty liver disease (NAFLD) is a major complication linked with the metabolic syndrome associated with dyslipidemia, inflammation, and oxidative stress. Impact of type 2 diabetes with hyperlipidemia in NAFLD has to be established, as well as the utility of commonly prescribed anti-diabetic and lipid-lowering agents in improving liver injury markers. Genetic type 2 diabetic Goto-Kakizaki rats were fed with a high-fat diet to test hepatic effects of type 2 diabetes with hyperlipidemia and the effect of atorvastatin and insulin, individually and in combination, in systemic and hepatic inflammatory and oxidative stress markers. High-fat diet aggravated fasting glycemia, systemic and liver lipids, and inflammatory and oxidative stress markers. Individual treatments improved glycemic and lipid profiles, but failed to improve inflammatory markers, whereas insulin was able to reduce liver oxidative stress parameters. Combination of insulin and atorvastatin further improved glycemic and lipid profiles and decreased circulating C-reactive protein levels and liver inflammatory and oxidative stress markers. Insulin and atorvastatin combination leads to better glycaemic and lipid profiles and to better protection against liver inflammation and oxidative stress, giving a superior level of liver protection in type 2 diabetic with hyperlipidemia.

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Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk—the PIOSTAT Study

Cited by 67 publications

References 32 publications

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

Simvastatin Improves Flow-Mediated Dilation but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

Pilot Study for the Evaluation of Morphological and Functional Changes in Retinal Blood Flow in Patients with Insulin Resistance and/or Type 2 Diabetes Mellitus

A role for atorvastatin and insulin combination in protecting from liver injury in a model of type 2 diabetes with hyperlipidemia

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