Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children

Abstract

Background This study tested the association between serum levels of microRNA-486, −146b and -15b and betatrophin in normal and obese children with/without type 2 diabetes mellitus (T2DM). Methods the study included 120 children; divided into three groups: G1 (50 healthy), G2 (35 obese) and G3 (35 obese with T2DM). The levels of microRNA-486, 146b and 15b and serum betatrophin were measured by their corresponding methods. Results serum microRNA-486, −146b, −15b and betatrophin levels were significantly high in G3 followed by G2 then G1 (p = 0.002, > 0.001, > 0.001, and > 0.001, respectively). Especially in G3, these levels correlated positively with the BMI percentile (r = 0.44, 0.58, 0.38, and 0.46, p = 0.007, > 0.001, 0.021, and 0.005, respectively), serum glucose (r = 0.56, 0.49, 0.82, 0.60, and 0.42, p > 0.001, 0.003, > 0.001, and > 0.001, respectively) and HbA1c% (r = 0.56, 0.39, 0.66, and 0.42, p > 0.001, 0.019, > 0.001, and 0.032, respectively) while, showed negative correlations with correlated with serum insulin levels (r = − 0.37, − 0.42, − 0.58, and − 0.41, p = 0.021, 0.012, > 0.001 and 0.013, respectively) and with serum C-peptide levels (r = − 0.76, − 0.50, − 0.35 and − 0.42, p > 0.001, 0.002, 0.036 and 0.011, respectively). Serum betatrophin levels correlated positively with microRNA-486, −146b and -15b levels in G2 (r = 0.35, 0.80, and 0.67, p = 0.036, > 0.001, and,> 0.001, respectively), and in G3 (r = 0.57, 0.36, and 0.38, p > 0.001, 0.029 and, 0.023, respectively). Conclusions Circulating microRNA-486, 146b and 15b increase significantly in obese children with T2DM and these levels correlate positively with serum betatrophin levels. Further studies are required to test the role of targeting of these microRNAs and betatrophin in the timely management of obesity and/or T2DM in children.

High fructose exposure modifies the amount of adipocyte-secreted microRNAs into extracellular vesicles in supernatants and plasma

“…The miR-146b is a miRNA conserved between rats and humans. A study in obese children and adult T2DM showed high miR-146b-5p levels in the total plasma, which was found that participated in the suppression of high concentration glucoseinduced pancreatic insulin secretion (Cui et al, 2018;Mohany et al, 2020). Interestingly, we found a negative correlation between the levels of miR-146b-5p in EVs and leptin in plasma.…”

Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study

“…MicroRNAs (miRs) are short non-coding sequences of nucleotides that can modulate the process of adipogenesis and many of its related consequences [ 11 ]. Abnormal expressions of microRNAs have been reported by many previous studies in obese individuals with/without diabetes [ 5 , 12 ]. Of these microRNAs, miR-29a was found to correlate with insulin resistance and inflammatory parameters in obese adults with/without T2DM [ 13 – 15 ].…”

“…The G3 participants had been managed only by life-style adjustments (those who had received any drug interventions were excluded from the study). Also, exclusion criteria included those who presented with T1DM, genetic or endocrinal disorders, inflammatory, or any other systemic illness [ 12 ].…”

“…qRT-PCR was done at 50 °C for 2 min and 95 °C for 10 min, followed by 40 cycles at 95 °C for 15 s and 60 °C for 1 min. The cel-miR-39 was used as an internal control during the quantification using specific stem-loop primers for miR-29a and miR-122 [ 5 , 12 ].…”

“…The analysis of the results was performed using Sequence Detection Software version 2.3 (Applied Biosystems). The difference in the expression levels of miR-29a and miR-122 between samples was calculated using the 2 -ΔΔCT method [ 5 , 12 ].…”