MiRNA-200a and miRNA-200b expression, and vitamin-D level: Prognostic significance in obese non-diabetic and obese type 2 diabetes mellitus individuals

Background: Obesity and type 2 diabetes mellitus (T2DM) are frequent co-occurring disorders that affect regular metabolic functions. Obesity has also been linked to an increased risk of developing diabetes. Obesity and diabetes are on the rise, increasing healthcare costs and raising mortality rates. Research has revealed that the expression profile of microRNAs (miRNAs) changes as diabetes progresses. Furthermore, vitamin D may have an anti-obesity effect and inverse association with body weight and body mass index (BMI). Low vitamin D levels do not solely cause obesity, which could be a factor in the etiology of T2DM.

Aim: To evaluate miRNA-200a and miRNA-200b expression, and vitamin-D levels in obese and obese T2DM individuals.

Methods: This study included 210 participants, of which, 82 were obese (BMI > 30 kg/m²) without T2DM, 28 were obese with T2DM, and 100 were healthy controls. BMI was evaluated and both fasting and postprandial blood glucose were used to confirm T2DM. Exosomal miRNA-200a and miRNA-200b expression were analyzed using real-time PCR using Taqman probes, and vitamin-D levels were evaluated using an electrochemiluminescence-based immunoassay technique. All data analyses were performed using SPSS 20.0 and GraphPad Prism 5 software.

Results: Overall, a 2.20- and 4.40-fold increase in miRNA-200a and miRNA-200b expression was observed among participants compared to healthy controls. MiRNA-200a and miRNA-200b expression among obese participants increased 2.40-fold and 3.93-fold, respectively, while in obese T2DM participants these values were 2.67-fold, and 5.78-fold, respectively, and these differences were found to be statistically significant (P = 0.02) (P < 0.0001). Obese participants showed a vitamin D level of 34.27 ng/mL, while in obese-T2DM participants vitamin D level was 22.21 ng/mL (P < 0.0001). Vitamin D was negatively correlated with miRNA-200a (r = -0.22, P = 0.01) and miRNA-200b (r = -0.19, P = 0.04). MiRNA-200a sensitivity was 75%, and specificity was 57%, with a cutoff value of 2.07-fold. MiRNA-200b sensitivity was 75%, and specificity was 71% with a cutoff value of 4.12-fold, suggesting that miRNA-200a and miRNA-200b with an increased expression of 2.07- and 4.12-fold could be predictive indicators for the risk of diabetes in obese participants.

Conclusion: MiRNA-200a and miRNA-200b were higher in diabetic obese participants vs non-diabetic obese participants, and insufficient vitamin D levels in obese T2DM participants may be involved in poor clinical outcome.