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Analysis of Circulating miRNA Expression Profiles in Type 2 Diabetes Patients with Diabetic Foot Complications
Giovanny Fuentevilla-Alvarez1, María Elena Soto2,3, Gustavo Jaziel Robles-Herrera4
1Endocrinology Department, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1. Col. Sección XVI, Mexico City 14080, Mexico.
Abstract:
Type 2 diabetes mellitus (T2DM) is associated with various complications, including diabetic foot, which can lead to significant morbidity and mortality. Non-healing foot ulcers in diabetic patients are a major risk factor for infections and amputations. Despite conventional treatments, which have limited efficacy, there is a need for more effective therapies. MicroRNAs (miRs) are small non-coding RNAs that play a role in gene expression and have been implicated in diabetic wound healing. miR expression was analyzed through RT-qPCR in 41 diabetic foot Mexican patients and 50 controls. Diabetic foot patients showed significant increases in plasma levels of miR-17-5p (p = 0.001), miR-191-5p (p = 0.001), let-7e-5p (p = 0.001), and miR-33a-5p (p = 0.005) when compared to controls. Elevated levels of miR-17, miR-191, and miR-121 correlated with higher glucose levels in patients with diabetic foot ulcers (r = 0.30, p = 0.004; r = 0.25, p = 0.01; and r = 0.21, p = 0.05, respectively). Levels of miR-17 showed the highest diagnostic potential (AUC 0.903, p = 0.0001). These findings underscore the possible role of these miRs in developing diabetes complications. Our study suggests that high miR-17, miR-191, and miR-121 expression is strongly associated with higher glucose levels and the development of diabetic foot ulcers.
Insights
MicroRNAs (miRs) like miR-17, miR-191, and miR-121 are elevated in diabetic foot patients, correlating with higher glucose levels. These miRs show potential as biomarkers for diabetic complications.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Type 2 diabetes mellitus (T2DM) complications, such as diabetic foot ulcers, pose significant health risks, including infection and amputation.
- Current treatments for diabetic foot ulcers have limited efficacy, highlighting the need for novel therapeutic strategies.
- MicroRNAs (miRs) are key regulators of gene expression and are increasingly recognized for their role in wound healing and diabetes pathogenesis.
Purpose of the Study:
- To investigate the differential expression of specific microRNAs (miRs) in patients with Type 2 diabetes mellitus (T2DM) and diabetic foot ulcers (DFUs).
- To explore the correlation between elevated miR levels and glycemic control in T2DM patients with DFUs.
- To assess the diagnostic potential of identified miRs as biomarkers for diabetic foot complications.
Main Methods:
- Plasma samples were collected from 41 Mexican patients with T2DM and DFUs and 50 healthy controls.
- Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was employed to analyze the expression levels of selected miRs.
- Statistical analyses, including correlation and receiver operating characteristic (ROC) curve analysis, were performed to evaluate the findings.
Main Results:
- DFU patients exhibited significantly higher plasma levels of miR-17-5p, miR-191-5p, let-7e-5p, and miR-33a-5p compared to controls (p < 0.005 for all).
- Elevated levels of miR-17, miR-191, and miR-121 were positively correlated with higher blood glucose levels in DFU patients (r = 0.30 to 0.21, p ≤ 0.05).
- miR-17 demonstrated the highest diagnostic accuracy for diabetic foot ulcers, with an Area Under the Curve (AUC) of 0.903 (p = 0.0001).
Conclusions:
- Specific microRNAs, including miR-17, miR-191, and miR-121, are significantly upregulated in patients with diabetic foot ulcers.
- These upregulated miRs are strongly associated with poor glycemic control, suggesting a role in the development of T2DM complications.
- The identified miRs, particularly miR-17, hold promise as potential diagnostic biomarkers for early detection and management of diabetic foot complications.
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