Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes

Type 2 diabetes patients exhibit subclinical inflammation but the regulatory mechanisms are poorly understood. We sought to evaluate the role of miR-146a expression along with its downstream proinflammatory signals in relation to glycemic control and insulin resistance. Study subjects (n = 20 each) comprised of clinically well characterized Type 2 diabetes patients and control non-diabetic subjects. miRNA and mRNA expression levels were probed in peripheral blood mononuclear cells (PBMC) by Real-time RT-PCR and plasma levels of TNF alpha and IL-6 were measured by ELISA. The miR-146a expression levels were significantly decreased in PBMCs from patients with Type 2 diabetes compared to control subjects. Among the target genes of miR-146a, TRAF-6 mRNA expression was significantly increased in patients with Type 2 diabetes while there was no significant difference in the mRNA levels of IRAK1 in the study groups. In contrast, there were significantly increased levels of NF kappa B expression in patients with Type 2 diabetes. There was an increased trend in the levels of TNF alpha and IL-6 mRNA in patients with type 2 diabetes. While SOCS-3 mRNA levels increased, plasma TNF alpha and IL-6 levels were also significantly higher in patients with type 2 diabetes. miR-146a expression was negatively correlated to glycated hemoglobin, insulin resistance, TRAF6, and NF kappa B mRNA levels and circulatory levels of TNF alpha and IL-6. Reduced miR-146a levels are associated with insulin resistance, poor glycemic control, and several proinflammatory cytokine genes and circulatory levels of TNF alpha and IL-6 in Asian Indian Type 2 diabetic patients.