Dataset Information

Monocyte miRNAs Are Associated With Type 2 Diabetes.

ABSTRACT: miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role of miRNAs in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNA effect on incident T2D. Of 774 detected miRNAs, 6 (miR-22-3p, miR-33a-5p, miR-181c-5p, miR-92b-3p, miR-222-3p, and miR-944) were associated with prevalent T2D. For five of the six miRNAs (all but miR-222-3p), our findings suggest a dose-response relationship with impaired fasting glucose and T2D. Two of the six miRNAs were associated with incident T2D (miR-92b-3p: hazard ratio [HR] 1.64, P = 1.30E-03; miR-222-3p: HR 1.97, P = 9.10E-03) in the highest versus lowest tertile of expression. Most of the T2D-associated miRNAs were also associated with HDL cholesterol concentrations. The genes targeted by these miRNAs belong to key nodes of a cholesterol metabolism transcriptomic network. Higher levels of miRNA expression expected to increase intracellular cholesterol accumulation in monocytes are linked to an increase in T2D risk.

SUBMITTER: Parker DC

PROVIDER: S-EPMC8965663 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Monocyte miRNAs Are Associated With Type 2 Diabetes.

Parker Daniel C DC Wan Ma M Lohman Kurt K Hou Li L Nguyen Anh Tram AT Ding Jingzhong J Bertoni Alain A Shea Steve S Burke Gregory L GL Jacobs David R DR Post Wendy W Corcoran David D Hoeschele Ina I Parks John S JS Liu Yongmei Y

Diabetes 20220401 4

miRNAs are small noncoding RNAs that may contribute to common diseases through epigenetic regulation of gene expression. Little is known regarding the role of miRNAs in type 2 diabetes (T2D). We performed miRNA sequencing and transcriptomic profiling of peripheral monocytes from the longitudinal Multi-Ethnic Study of Atherosclerosis (MESA) (N = 1,154). We examined associations between miRNAs and prevalent impaired fasting glucose and T2D and evaluated the T2D-associated miRNA effect on incident ...[more]

PMID: 35073575

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Project description:BackgroundGestational diabetes mellitus (GDM) is a serious public health issue affecting 9-15% of all pregnancies worldwide. Recently, it has been suggested that extracellular vesicles (EVs) play a role throughout gestation, including mediating a placental response to hyperglycaemia. Here, we investigated the EV-associated miRNA profile across gestation in GDM, assessed their utility in developing accurate, multivariate classification models, and determined the signaling pathways in skeletal muscle proteome associated with the changes in the EV miRNA profile.MethodsDiscovery: A retrospective, case-control study design was used to identify EV-associated miRNAs that vary across pregnancy and clinical status (i.e. GDM or Normal Glucose Tolerance, NGT). EVs were isolated from maternal plasma obtained at early, mid and late gestation (n = 29) and small RNA sequencing was performed. Validation: A longitudinal study design was used to quantify expression of selected miRNAs. EV miRNAs were quantified by real-time PCR (cases = 8, control = 14, samples at three times during pregnancy) and their individual and combined classification efficiencies were evaluated. Quantitative, data-independent acquisition mass spectrometry was use to establish the protein profile in skeletal muscle biopsies from normal and GDM.ResultsA total of 2822 miRNAs were analyzed using a small RNA library, and a total of 563 miRNAs that significantly changed (p < 0.05) across gestation and 101 miRNAs were significantly changed between NGT and GDM. Analysis of the miRNA changes in NGT and GDM separately identified a total of 256 (NGT-group), and 302 (GDM-group) miRNAs that change across gestation. A multivariate classification model was developed, based on the quantitative expression of EV-associated miRNAs, and the accuracy to correctly assign samples was > 90%. We identified a set of proteins in skeletal muscle biopsies from women with GDM associated with JAK-STAT signaling which could be targeted by the miRNA-92a-3p within circulating EVs. Interestingly, overexpression of miRNA-92a-3p in primary skeletal muscle cells increase insulin-stimulated glucose uptake.ConclusionsDuring early pregnancy, differently-expressed, EV-associated miRNAs may be of clinical utility in identifying presymptomatic women who will subsequently develop GDM later in gestation. We suggest that miRNA-92a-3p within EVs might be a protected mechanism to increase skeletal muscle insulin sensitivity in GDM.

Project description:Background: Recently, monocyte to high-density lipoprotein cholesterol ratio (MHR) as a novel inflammatory biomarker has drawn lots of attention. This study was conducted in patients with type 2 diabetes mellitus (T2DM) to investigate the correlation between MHR and metabolic-associated fatty liver disease (MAFLD). Methods: Totally, 1,051 patients with T2DM from the Affiliated Hospital of Jiangsu University were enrolled and classified as MAFLD (n = 745) group and non-MAFLD (n = 306) group according to the MAFLD diagnostic criteria. In contrast, patients were also separated into four groups based on MHR quartiles. Anthropometric and biochemical measurements were performed. The visceral fat area (VFA) and subcutaneous fat area (SFA) of participants were measured by dual bioelectrical impedance. Fatty liver was assessed by ultrasonography. Results: The MHR level of subjects in the MAFLD group was statistically greater than that in the non-MAFLD group (P < 0.05). Meanwhile, MHR was higher in the overweight or obese MAFLD group compared with that in the lean MAFLD group (P < 0.05). The area under the ROC Curve (AUC) assessed by MHR was larger than that of other inflammatory markers (P < 0.01). The cutoff value of MHR was 0.388, with a sensitivity of 61.74% and a specificity of 56.54%. For further study, binary logistic regression analyses of MAFLD as a dependent variable, the relationship between MHR and MAFLD was significant (P < 0.01). After adjusting for many factors, the relationship still existed. In the four groups based on MHR quartiles, groups with higher values of MHR had a significantly higher prevalence of MAFLD (P < 0.05). The percentage of patients with obese MAFLD increased as the MHR level increased (P < 0.01). Among different quartiles of MHR, it showed that with the increasing of MHR, the percentage of patients with MAFLD who had more than four metabolic dysfunction indicators increased, which was 46.39, 60.52, 66.79, and 79.91%, respectively, in each quartile. Conclusion: Monocyte to high-density lipoprotein cholesterol ratio is a simple and practicable inflammatory parameter that could be used for assessing MAFLD in T2DM. T2DM patients with higher MHR have more possibility to be diagnosed as MAFLD. Therefore, more attention should be given to the indicator in the examination of T2DM.

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Monocyte miRNAs Are Associated With Type 2 Diabetes.

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Monocyte miRNAs Are Associated With Type 2 Diabetes.

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