Short Report: Circulating microRNAs are associated with incident diabetes over 10 years in Japanese Americans

Abstract

Epigenetic changes precede the development of diabetes by many years, providing clues to its pathogenesis. We explored whether the epigenetic markers, circulating microRNAs (miRNAs), were associated with incident diabetes in Japanese Americans. We conducted a pilot study (n = 10) using plasma from age-and sex-matched participants who did or did not develop diabetes in the Japanese American Community Diabetes Study, an observational study of diabetes risk factors. Extraction and high-throughput sequencing of miRnAs were performed using samples collected at baseline. Regression models were fit comparing circulating miRNAs (N = 1640) among individuals who did or did not develop incident diabetes at 10-year follow-up. Participants averaged 51.7 years of age at baseline; 60% were male. We identified 36 miRNAs present at different (10 higher and 26 lower) levels in individuals who developed diabetes compared to those who did not (log 2 fold change ≥1.25 and false discovery rate ≤5%). These included miRNAs with functions in skeletal muscle insulin metabolism (miR-106b and miR-20b-5p) and miRNAs with functions in both skeletal muscle insulin metabolism and cell cycle regulation in endocrine pancreas (miR-15a and miR-17). Circulating miRNAs were associated with subsequent development of diabetes among Japanese Americans over 10 years of follow-up. Results are preliminary. Large-scale miRNA sequencing studies could inform our understanding of diabetes pathogenesis and development of therapies, based on gene expression regulation, that target diabetes. open Scientific RepoRtS | (2020) 10:6509 | https://doi.www.nature.com/scientificreports www.nature.com/scientificreports/ participants. These values were very similar between the groups (Matsuda 3.1 ± 0.7 vs. 3.2 ± 1.3, p = 0.879; IGI 0.8 ± 1.0 vs. 0.7 ± 0.4, p = 0.883), suggesting that differences in baseline miRNA levels were unlikely to be attributable to differences in glucose tolerance at baseline, despite the differing distributions of IFG and IGT.This analysis demonstrates the utility of measuring circulating miRNAs with RNA sequencing from observational and interventional studies of type 2 diabetes to characterize changes that precede the development of diabetes. Results can be carried forward in the development of predictive biomarkers of future type 2 diabetes.

Circulating microRNA profile in humans and mice with congenital GH deficiency

“…The miR-199a is also increased in serum of patients with type 2 diabetes mellitus (T2DM) and inhibits GLUT4 expression in vitro (Yan et al, 2014). Serum miR-4732 has also been linked with diabetes in humans (Wander et al, 2020 a LogFC: difference of the mean of logarithm of the of fold change of the compared groups.…”

“…The miR‐199a is also increased in serum of patients with type 2 diabetes mellitus (T2DM) and inhibits GLUT4 expression in vitro (Yan et al, 2014). Serum miR‐4732 has also been linked with diabetes in humans (Wander et al, 2020). As previously mentioned, IGHD individuals have high insulin sensitivity with low insulin concentrations (Oliveira et al, 2012).…”

A data-driven biocomputing pipeline with meta-analysis on high throughput transcriptomics to identify genome-wide miRNA markers associated with type 2 diabetes

“…A recent high throughput plasma sequencing study revealed the down-regulation of three of the circulating miRNAs present in the identified meta-signature (hsa-miR-15b-5p, hsa-miR-106b-3p, hsa-miR-106b-5p), in association with incident T2D [38]. Multiple studies attest to the upregulation of hsa-miR-33b-5p in circulatory and adipose tissues in the presence of dysglycemia.…”

Effects of physical activity on cell‐to‐cell communication during type 2 diabetes: A focus on miRNA signaling

“…For example, myomiRNA-7, myomiRNA-96, and myomiRNA-124a have been recognized to alter pancreatic β-cell [42,43], while myomiRNA-26, myomiRNA-148, my-omiRNA-182, and myomiRNA-483 stimulated insulin gene transcription [44,45]. Recently, a short report showed that circulating miRNAs with functions in skeletal muscle (miRNA-106b and miRNA-20b-5p) were associated with development of diabetes [46]. Those data are related to Japanese American cohort as epigenetic marker for diabetes development [46].…”

“…Recently, a short report showed that circulating miRNAs with functions in skeletal muscle (miRNA‐106b and miRNA‐20b‐5p) were associated with development of diabetes [46]. Those data are related to Japanese American cohort as epigenetic marker for diabetes development [46]. Changes in miRNA releases by the muscle could be implicated in pancreas dysfunction and the progression of T2D.…”