Adipose and Plasma microRNAs miR-221 and 222 Associate with Obesity, Insulin Resistance, and New Onset Diabetes after Peritoneal Dialysis

Abstract

Background: The correlation between microRNA, obesity, and glycemic intolerance in patients on peritoneal dialysis (PD) is unknown. We aimed to measure the adipose and plasma miR-221 and -222 levels, and to evaluate their association with adiposity, glucose intolerance, and new onset diabetes mellitus (NODM) after the commencement of PD. Methods: We prospectively recruited incident adult PD patients. miR-221 and -222 were measured from adipose tissue and plasma obtained during PD catheter insertion. These patients were followed for 24 months, and the outcomes were changes in adiposity, insulin resistance, and NODM after PD. Results: One hundred and sixty-five patients were recruited. Patients with pre-existing DM had higher adipose miR-221 (1.1 ± 1.2 vs. 0.7 ± 0.9-fold, p = 0.02) and -222 (1.9 ± 2.0 vs. 1.2 ± 1.3-fold, p = 0.01). High adipose miR-221 and -222 levels were associated with a greater increase in waist circumference (miR-221: beta 1.82, 95% CI 0.57–3.07, p = 0.005; miR-222: beta 1.35, 95% CI 0.08–2.63, p = 0.038), Homeostatic Model Assessment for Insulin Resistance (HOMA) index (miR-221: beta 8.16, 95% CI 2.80–13.53, p = 0.003; miR-222: beta 6.59, 95% CI 1.13–12.05, p = 0.018), and insulin requirements (miR-221: beta 0.05, 95% CI 0.006–0.09, p = 0.02; miR-222: beta 0.06, 95% CI 0.02–0.11, p = 0.002) after PD. The plasma miR-222 level predicted the onset of NODM (OR 8.25, 95% CI 1.35–50.5, p = 0.02). Conclusion: miR-221 and -222 are associated with the progression of obesity, insulin resistance, and NODM after PD.

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

“…The identified hub gens, TFs and miRNAs might be involved in the pathological process of AKI. PPP1CC [549], E2F1 [543], EEF1A2 [538], VCAM1 [626], CDH1 [622], AGTR1 [79], SNCA (synuclein alpha) [574], hsamir-221 [780], YY1 [781], STAT3 [782] [787], STAT3 [788] and BRCA1 [789] were significantly associated with cardiovascular disorders. E2F1 [265], BMI1 [260], VCAM1 [321], AGTR1 [64], hsa-mir-638 [790], hsa-mir-221 [791], FOXC1 [792], YY1 [793], STAT3 [794] and BRCA1…”

“…The identified hub gens, TFs and miRNAs might be involved in the pathological process of AKI. PPP1CC [549], E2F1 [543], EEF1A2 [538], VCAM1 [626], CDH1 [622], AGTR1 [79], SNCA (synuclein alpha) [574], hsa-mir-221 [780], YY1 [781], STAT3 [782] and PDX1 [783] are closely involved with diabetes mellitus. E2F1 [110], BMI1 [95], EEF1A2 [104], ACTA1 [128], VCAM1 [220], AGTR1 [58], hsa-mir-221 [784], MEF2A [785], FOXC1 [786], YY1 [787], STAT3 [788] and BRCA1 [789] were significantly associated with cardiovascular disorders.…”

“…E2F1 [496], AGTR1 [74], VCAM1 [533], hsa-mir-7847-3p [804], FOXC1 [805], USF2 [796], YY1 [806], STAT3 [807] and BRCA1 [799] have been observed in sepsis patients. Studies have shown that E2F1 [669], VCAM1 [715], AGTR1 [83], hsa-mir-221 [780], YY1 [808], STAT3 [809], PDX1 [810] and BRCA1 [811] are associated with obesity. E2F1 [719] and VCAM1 [736] are altered expressed in patients with renal ischemia.…”

Metformin: From Diabetes to Cancer—Unveiling Molecular Mechanisms and Therapeutic Strategies

“…Additionally, in a cross-sectional study, metformin treatment was associated with changes in the circulating profiles of miR-192, miR-222, and mir-140-5p, paralleled by decreases in fasting glucose and HbA1c levels [85]. Circulating levels of miR-192 have previously been suggested as potential biomarkers of T2DM and miR-222 has been associated with the progression of obesity and insulin resistance [86]. Metformin also enhances hepatic redox balance by elevating the ratio of reduced glutathione to oxidized glutathione.…”

Role of micro‐RNAs associated with adipose‐derived extracellular vesicles in metabolic disorders

“…In addition, miR-222 could also be related to liver cancer and a dual effect of ADEV-containing miR-222 on liver physiopathology during obesity has been described. [102][103][104][105] Furthermore, ADEV-containing miR-27a promoted liver cancer by targeting forkhead box protein O1 (Foxo1) and extracellular miR-23a/b also amplified cancer progression by targeting the tumor suppressor Von Hippel-Lindau (VHL). 106,107 Interestingly, miR-23a was also involved in IR, by targeting phosphatase and tensin homolog (Pten) and S6 kinase (S6k), 108 which could also support a correlation between cancer development and obesity-related disease.…”