Publication: ROLES OF SALIVARY MICRORNAS AS POTENTIAL NON-INVASIVE BIOMARKERS IN ASSESSING EFFECTIVENESS OF COMBINED THERAPY WITH GLICLAZIDE AND METFORMIN REGIMEN AMONG OBESE TYPE 2 DIABETES MELLITUS (T2DM) PATIENTS
Date
2024
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Publisher
IMU University
Abstract
In Malaysia, the rising incidence of type 2 diabetes mellitus (T2DM) among adolescent and adults is linked to obesity. Pharmaceutical therapy has been brought in to curb T2DM, more famously in the form of biguanides (metformin) and sulfonylureas (gliclazide). However, variation in the individual glycaemic response to metformin treatment might be due to heritability factors. Importantly, metformin has been reported to alter the microRNA (miRNA) expression profiles. Thus, the present study aims to provide data on differential expression of salivary miRNAs in responders and non-responders among T2DM patients under combined treatment of metformin and gliclazide. A total of 50 subjects were recruited each for responder and non-responder groups at the endocrine clinic of the Hospital Canselor Tuanku Mukhriz Universiti Kebangsaan Malaysia (HCTM). Subjects with HbA1c reduction levels of 0.5% or more were categorised as responders. The patients' demographic data including age, gender, BMI, WHR, ethnicity, smoking status, exercise routine and medical history were recorded. Total RNAs were isolated from the saliva collected and pooled prior to reverse-transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The levels of microRNA namely, miR 28-3p, miR 135a-5p, miR 126-5p, and miR 320a3p were determined using RNU6P as the endogenous control. Pearson's corelation coefficient analysis demonstrated significant (p<0.05) positive correlation between BMI (29.2 ± 1.25 kg/m2) and HbA1c reduction levels (0.78 ± 0.36%) and between WHR (0.91 ± 1.35) and HbA1c reduction, while age and HbA1c reduction had a negative correlation r = -0.126 with p-value = 0.008. Meanwhile Pearson's chi-square test demonstrated only smoking status (p<0.001) had a significant correlation with the HbA1c reduction levels. Based on the miRNA PCR assays, miR 135a-5p, miR 1265p, and miR 320a-3p were upregulated while miR 28-3p was downregulated in responders compared to non-responder regardless on ethnicity and smoking status. Among the Malay subjects, miR-126-5p was downregulated in the responders among smokers but upregulated in the responders among the non-smokers when compared to their counterparts of non-responder groups. Interestingly, smoking status was also found to be significantly correlated with the HbA1c reduction levels. The deregulation and upregulation of these four targeted miRNAs have been recognized as a contributing factor in several pathways across T2DM spectrum, encompassing insulin resistance, adherens junction, hippo signalling, and AMPK signalling, proposing these four targeted miRNAs to be potential biomarkers of T2DM while miR-126-5p downregulation within VEGF pathway should be researched further and within various ethnic groups as an indicator for both T2DM with smoking-related diseases.
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Keywords
Diabetes Mellitus, Type 2, Adolescent, Adult, Gliclazide, Metformin, Obesity, Biomarkers, MicroRNAs, Insulin Resistance