Co-administration of vitamin E and atorvastatin improves insulin sensitivity via peroxisome proliferator-activated receptor γ in hyperlipidemic type 2 diabetic patients: a randomized double-blinded clinical trial

Abstract

Background: Contrary to the reports about the useful effects of atorvastatin on blood lipids and insulin sensitivity by up-regulation of peroxisome proliferative-activated receptor gamma (PPAR-γ) expression, to our knowledge, there is inconclusive results about vitamin E. Also, there is no study to assess co-administration of vitamin E and atorvastatin on PPAR-γ mRNA expression, insulin sensitivity and lipid profile in diabetic patients. We compared this effect in hyperlipidemic subjects with type 2 diabetes mellitus (T2DM). Methods: At the present randomized clinical trial (RCT), 30 T2DM women with hyperlipidemia were categorized into the treated group with 20 mg atorvastatin plus 400 IU vitamin E supplement (n = 15) or atorvastatin plus placebo (n = 15) per day for 12 weeks. Anthropometric and biochemical measures were done at the baseline and after the 12-week intervention. PPAR-γ mRNA expression was measured in the peripheral blood mononuclear cells (PBMCs) of all patients. Results: After adjusting for the baseline measures, vitamin E resulted in significant improvements in insulin sensitivity in terms of HOMA-IR (-1.01±0.52 vs. -2.56 ± 0.54, P = 0.04) and serum insulin (-0.55±0.35 vs. -6.5 ± 1.3, P < 0.001), compared with the atorvastatin plus placebo. Adjusted for the baseline variables, compared with the atorvastatin plus placebo, vitamin E supplementation could up-regulate PPAR-γ mRNA expression (OR=5.4, 95% CI=0.8-36.9, P=0.04) in PBMC of T2DM women. Conclusions: Vitamin E supplementation along with atorvastatin may improve insulin sensitivity through up-regulation of PPAR-γ gene. More RCTs are needed to reach conclusive results. Trial registration: The present study is registered under ClinicalTrials.gov Identifier no. IRCT20170918036256N1.

Key Nutrients for Optimal Blood Glucose Control and Mental Health in Individuals with Diabetes: A Review of the Evidence

“…In a trial of healthy adults, it was found that a high dose of vitamin E supplementation (300 mg/d) reduced lipid peroxidation [ 107 ], while another study showed that the simultaneous administration of Vitamins E and C resulted in reduced inflammation and enhanced insulin action by promoting non-oxidative glucose metabolism [ 108 ]. In several studies, when vitamin E was co-administered with atorvastatin and vitamin C in people with type 2 diabetes, blood glucose levels decreased [ 109 , 110 ].…”

Identification of stable reference genes in peripheral blood mononuclear cells from type 2 diabetes mellitus patients

“…A stable reference gene is expected to not show inter-subject variation or be affected by the disease condition 21 , 22 . Glyceraldehyde-3-Phosphate Dehydrogenase ( GAPDH ), is extensively used as a reference gene for measuring relative gene expression in PBMCs from diabetics 23 – 25 . Nevertheless, multiple studies have reported that hyperglycaemia can alter GAPDH expression in cultured cells and animal models 26 – 28 .…”

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for measuring relative gene expression in PBMCs from diabetics [23][24][25] . Nevertheless, multiple studies have reported that hyperglycaemia can alter GAPDH expression in cultured cells and animal models [26][27][28] .Meticulous selection of reference genes is of utmost importance for accurate analysis of gene expression data.

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“…for measuring relative gene expression in PBMCs from diabetics [23][24][25] . Nevertheless, multiple studies have reported that hyperglycaemia can alter GAPDH expression in cultured cells and animal models [26][27][28] .…”