Dietary Regulation of miR-33b and miR-29a in Relationship to Metabolic Biomarkers of Glucose and Lipids in Obese Diabetic Women: A Randomized Clinical Controlled Study

Abstract

Background: MicroRNAs have recently been introduced as epigenetic regulators of glucose and lipid metabolic pathways, which are impaired in obesity and diabetes. Objectives: We evaluated the effects of calorie-restricted diet therapy on the circulating levels of miR-33b and miR-29a in relationship to glucose and lipid metabolic parameters in obese patients with type 2 diabetes mellitus (T2DM). Methods: This randomized clinical controlled trial was performed on 30 eligible obese women with T2DM, randomly divided into two groups (control group, n = 15; diet therapy group, n = 15) for 10 weeks. Ten healthy women with normal weight were enrolled at the baseline of the study as controls. Demographic information, dietary intake, and anthropometric and biochemical indices were obtained before and after the study. Circulating miR-33b and miR-29a were assessed for all subjects using quantitative RT-PCR, and the fold change of each circulating miRNA was compared between groups. Results: The circulating levels of miR-29a and miR-33b in the diabetic women were higher (0.40-fold) and lower (1.43-fold), respectively, than normal levels. Diet therapy significantly increased the circulating level of miR-33b (P = 0.023, 0.97-fold upregulation) to normal levels. This increase was independently correlated with caloric restriction (95%CI: -0.004 to -0.0001, P = 0.022) and 2hPPBS (95%CI: -0.009 to -0.001, P = 0.035). No remarkable change was observed in circulating levels of miR-29a. Conclusions: Our findings introduced a novel therapeutic effect of diet therapy on circulating miRNAs in obese patients with T2DM. MiR-33b is an important therapeutic target in the treatment and prevention of T2DM and its complications.

Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention

“…Other researchers have also studied the relationship between miR-33b levels and obesity-induced insulin resistance. One study reported that miR-33b levels were lower in diabetic obese women compared to levels in healthy normal-weight women, and this effect could be reversed by changing dietary habits that lead to reduced weight [ 86 ]. Additionally, an analysis of plasma miR-33b levels in patients with diabetic dyslipidaemia and insulin resistance indicated that miR-33b showed a positive correlation with plasma insulin levels and triglycerides, and a negative tendency with HDL cholesterol; these authors suggested that targeting miR-33b using antisense therapy could help to reduce hyperinsulinemia and prevent low HDL levels [ 87 ].…”