Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects With Impaired Glucose Tolerance and Patients With Type 2 Diabetes

PLoS One. 2015 May 28;10(5):e0128372. doi: 10.1371/journal.pone.0128372. eCollection 2015.

Abstract

Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Case-Control Studies
  • Cholesterol / blood
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Ethnic Groups
  • Fasting
  • Female
  • Gene Expression Regulation
  • Glucose Intolerance
  • Glucose Tolerance Test
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Phenotype*
  • Prediabetic State / blood*
  • Prediabetic State / ethnology
  • Prediabetic State / genetics
  • Prediabetic State / pathology

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • MIRN128 microRNA, human
  • MIRN130 microRNA, human
  • MIRN374 microRNA 374, human
  • MIRN423 microRNA, human
  • MicroRNAs
  • hemoglobin A1c protein, human
  • Cholesterol

Grant support

Authors acknowledge the financial support from the Department of Biotechnology (DBT), Government of India. This work was also supported by grants from the French Fondation pour la Recherche Médicale (FRM-20101220456) and is supported by the French—Indian medical research cooperation program between INSERM and ICMR. The authors thank the study participants, and the clinical assistants and administrative personnel at the Madras Diabetes Research Foundation, Chennai, India.