Circulating MicroRNAs linked to type 2 diabetes
Francisco J. Ortega, Ph.D., from the Institut d'Investagació Biomédica de Girona in Spain, and colleagues assessed the circulating miRNA profile in 12 men: six with normal glucose tolerance (NGT) and six with T2D. In an extended sample of 45 men with NGT and 48 with T2D, the association of 10 circulating miRNAs with T2D was validated cross-sectionally. Longitudinal validation was performed in 35 patients with T2D who were recruited in a randomized three-month metformin trial. In seven healthy volunteers, circulating miRNAs were also assessed before and after a six-hour hyperinsulinemic-euglycemic clamp and insulin plus intralipid/heparin infusion.
In patients with T2D, the researchers identified increases in three miRNAs and decreases in seven miRNAs. After controlling for confounders, miR-140-5p and miR-423-5p independently accounted for 49.5 percent of fasting glucose variance. A discriminant function of four miRNAs (miR-140-5p, miR-423-5p, miR-195, and miR-126) was specific for T2D, with 89.2 percent accuracy. Significant changes in circulating miR-192, miR-140-5p, and miR-22 were seen with metformin but not placebo, in parallel to reduced fasting glucose and glycated hemoglobin. Decreased miR-222 was seen with insulin infusion during clamp, while increases in circulating miR-222 and miR-140-5p were seen with the intralipid/heparin mixture.
"This study depicts the close association between variations in circulating miRNAs and T2D and their potential relevance in insulin sensitivity," the authors write.
The study was partially funded by an EFSD/Lilly Fellowship award.
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