Background/Aims
Circulating biomarkers with variable sensitivity/specificity are in use for prediction and stratification of type 2 diabetes (T2DM) and associated co-morbidities. MicroRNAs are short non-coding RNA that are shown to target metabolic pathways in obesity and T2DM. This study aims to identify specific disease-associated microRNAs that could help in the diagnosis/prognosis, and disease management in people with class 3 obesity and T2DM.
Methods
Plasma was collected (n=12) in people with class 3 obesity attending a weight management program (WMP) in Sydney, n=6 each, with and without T2DM at baseline and after 12-months of joining the WMP. Tests for biochemistry and HbA1c were carried-out at baseline and 12-months. We isolated RNA from these plasma samples and profiled a set of 754 known and validated microRNAs using OpenArray™ Platform. Plasma microRNA data was globally normalised and compared between baseline and 12-months from the same participants. Additional analyses involved identification of microRNAs associated with T2DM as well as with 12-month weight loss using penalised regression and bootstrapping methods.
Results
Participants were 50% female, 50% T2DM, aged 52±8.2 years, weight 146±19.6kg, BMI 56.2±12.9kg/m², AST 29.2±16U/L and ALT 34.5±14.8U/L. Significant weight loss was achieved at 12 months compared to baseline (134.05±17.1 vs 146±19.6kg,p=0.01) with significant reduction in HbA1c (6.2±1.9% vs 6.9±2.2%,p=0.03), with no change in 12-month AST 27.8±23.1U/L or ALT 32.0±16.4U/L. We identified a specific set of circulating microRNAs that are differentially expressed at 12-months compared to baseline. We also identified differences in relation to weight loss, HbA1c, liver enzymes and changes in other clinical and biochemical measurements.
Conclusions
A set of microRNAs was identified to be associated with class 3 obesity and T2DM. These studies present the potential of developing a panel of microRNA-based biomarkers that could also be explored for a diagnostic or prognostic role in class 3 obesity and T2DM.