Altered circulatory levels of miR-128, BDNF, cortisol and shortened telomeres in patients with type 2 diabetes and depression

Abstract

Aims: Several studies have reported the role of biomarkers either in diabetes or depression. The present study is aimed at profiling the circulating levels of miR-128, brain-derived neurotrophic factor (BDNF), cortisol and telomere length in patients with type 2 diabetes with and without depression compared to individuals with normal glucose tolerance. Methods: Study subjects (n = 160) were recruited from an ongoing epidemiological study in southern India. Non-diabetic and diabetic individuals were diagnosed as per the World Health Organization criteria. Depression score was derived using PHQ-12 questionnaire. Real-time quantitative PCR and ELISA methodologies were used to quantify the biomarkers. Results: Circulatory levels of miR-128 and cortisol were significantly (p < 0.05) increased with decreased BDNF levels and shortened telomeres in T2DM patients with or without depression compared to NGT individuals. T2DM patients with depression had the highest levels of miR-128 and cortisol and lowest levels of BDNF and telomere length compared to other groups. Pearson correlation analysis showed miR-128 levels were negatively associated with BDNF, telomere length and HDL cholesterol and positively correlated with cortisol, depression score, poor glycemic control and insulin resistance. Regression analysis confirmed that miR-128 was significantly associated with depression score even after adjusted for several confounding factors. However, this association was lost when adjusted for cortisol or telomere length. Conclusions: Patients with type 2 diabetes and depression exhibited increased circulatory levels of miR-128 and serum cortisol and decreased levels of BDNF and shortened telomeres. These neuroendocrine signatures were more markedly altered in those with combined diabetes and depression.