253-LB: Characterization of Korean Type 2 Diabetes as Hyperinsulinemic, Insulin-Resistant, and miR-10a/b-5p-Deficient Hyperglycemia

Background: We previously reported that miR-10a-5p and miR-10b-5p are key regulators in the development of type 2 diabetes (T2D). Deficiency of miR-10a-5p or miR-10b-5p triggers the onset of T2D in mice while restoration of their miRNAs remarkably rescues the diabetic symptoms including hyperglycemia by restoration of insulin production and sensitivity. Deficiency of the antidiabetic miR-10a-5p and miR-10b-5p was also observed in T2D patients in the United States. However, the miRNA levels have not been examined in Korean T2D patients.

Method: Plasma samples were obtained from 54 (32 males and 22 females) patients with T2D, 24 (17 males and 7 females) patients with prediabetes, and 38 (21 males and 17 females) healthy donors in South Korea. T2D patients were selected based on the criteria of elevated both fasting glucose (>125 mg/dL), and A1C (>6.5). We examined levels of miR-10a/b-5p and metabolic panels including insulin (INS) and its receptor (INSR) using qPCR, ELISA, and Western blot. For statistics, we used a one-way analysis of variance or the Kruskal-Wallis test.

Results: Plasma samples were grouped into T2D, prediabetes, and healthy controls by levels of both fasting glucose and A1C. Fasting glucose, A1C, C-peptide, and insulin were significantly elevated in the T2D patient group while miR-10a/b-5p and INSR were noticeably reduced compared to the prediabetic group and the healthy control group. The Spearman rank correlation analysis showed significant correlations between miR-10a/b-5p levels and metabolic parameters in T2D patients and. healthy controls. miR-10a/b-5p levels were positively correlated with INSR, but negatively correlated with glucose, INS, C-peptide, BMI, and age in T2D patients.

Conclusion: Korean T2D was defined as miR-10a/b-5p deficiency as well as increased insulin production and resistance through reduction of insulin receptor.