Type 2 diabetes mellitus (T2DM) is a progressive metabolic disorder initiated by insulin resistance, leading to compensatory hyperinsulinemia, beta-cell exhaustion, and chronic hyperglycemia. It is a major global health burden associated with macrovascular and microvascular complications. Dysregulation of the renin-angiotensin system (RAS), Antioxidant pathway, inflammation, and vitamin D signaling interact in a self-perpetuating metabolic loop driving disease progression. Hepatic insulin resistance plays a central role, while glucotoxic pathways distinguish T2DM from obesity. This review aims to examine the molecular cross-talk among the RAS, antioxidant pathway, inflammation, and vitamin D signaling pathways in T2DM pathogenesis. It seeks to clarify how their interactions drive insulin resistance, beta-cell dysfunction, and complications, thereby supporting the development of more precise, mechanism-based therapeutic strategies. The RAS plays a central role in T2DM through overactivation of the angiotensin-converting enzyme/angiotensin II/angiotensin II receptor type 1 (ACE/Ang II/AT1R) axis, promoting insulin resistance, beta-cell apoptosis, oxidative stress (OS), inflammation, and vascular damage, while the ACE2/Ang-(1-7)/Mas axis offers protective effects. Ang II-induced ROS production disrupts antioxidant defenses and accelerates glucotoxicity. Chronic low-grade inflammation, marked by increased interleukin-6 (IL-6) and reduced interleukin-10 (IL-10), further worsens metabolic dysfunction. Vitamin D receptor (VDR) signaling counteracts these effects by suppressing renin, reducing Ang II activity, enhancing antioxidant enzymes, and modulating inflammation. The liver serves as a key site where these pathways converge. Therapeutic strategies-including ACE inhibitors, angiotensin II receptor blockers (ARBs), GLP-1 receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, antioxidants, and vitamin D-target these interconnected mechanisms, with responses influenced by disease stage and sex differences. T2DM develops through interconnected dysregulation of four key pathways: the RAS, OS-antioxidant imbalance, chronic inflammation, and vitamin D/VDR signaling. These pathways interact to promote insulin resistance, beta-cell dysfunction, and vascular complications, driving progression from prediabetes to overt disease. Therapeutic strategies targeting these mechanisms-including RAS inhibitors, antioxidant-based interventions, metformin, and vitamin D supplementation-offer complementary benefits but have limitations and potential adverse effects. Treatment responses may vary by biological factors such as sex and disease stage, highlighting the need for well-designed clinical trials to enable precise, mechanism-based management.

Type 2 Diabetes Mellitus (T2DM) is becoming increasingly common, driven both by genetic and lifestyle factors. In India, changing lifestyles and urban habits have led to a sharp rise in cases. Since risk patterns differ across regions, assessing the diabetes risk of people living in and around Lucknow with the help of Indian Diabetes Risk Score (IDRS) will help to identify the vulnerable individuals and support timely prevention and management of T2DM. This study aimed to assess the Type 2 Diabetes Mellitus (T2DM) risk in individuals using the Indian Diabetes Risk Score (IDRS) and to evaluate its association with various factors such as age, gender, Body Mass Index (BMI), family history of diabetes, physical activity, waist circumference, and Random Blood Sugar (RBS) levels. A cross-sectional study was conducted from February to August 2023 in various departments of the University of Lucknow and King George’s Medical University, Lucknow. A total of 795 participants were recruited through systematic random sampling. The IDRS was applied to assess diabetes risk, and statistical analyses were performed to explore associations between IDRS and various risk factors. Among the participants, about 18.5

Epigenetic factors, especially microRNAs (miRNAs), are gaining attention as promising biomarkers for disease prediction, detection, and monitoring. Variations in circulating miRNA levels have been linked to pre-diabetes, diabetes, and associated complications, showing their potential as early indicators of disease. The aim of the present study is to investigate the potential of hsa-miR-377-3p, hsa-miR-513a-3p, and hsa-miR-30b-5p as early biomarkers for identifying people at risk of type 2 diabetes (T2DM) and to look into how they contribute to the pathophysiology of the disease. The current case-control study involved 104 participants, categorized into pre-diabetic (N = 20), diabetic (N = 40), and healthy controls (N = 44), recruited from King Georges’ Medical University, India. Proper ethical approval and informed consent were obtained. Participants were assessed based on fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) levels. Serum samples were collected for biochemical analysis and miRNA isolation. The expression of particular miRNAs related to antioxidant pathways was investigated using quantitative real-time PCR. Significant differences were observed in clinical parameters among the study groups. Diabetic individuals exhibited elevated FPG and HbA1c levels compared to pre-diabetics and controls. Notably, miRNAs viz. hsa-miR-377-3p, hsa-miR-513a-3p, and hsa-miR-30b-5p were identified as potential biomarkers linked to T2DM pathogenesis and antioxidant regulation. The study highlighted the role of these miRNAs in the development of diabetes-related complications and their potential as therapeutic targets. The findings exhibited the necessity for early identification of individuals at risk for T2DM through miRNA profiling. This study contributes in the development of innovative diagnostic and treatment approaches as well as the comprehension of the molecular mechanisms underlying T2DM.

Background Type 2 diabetes mellitus (T2DM) is associated with oxidative stress and altered gene expression, particularly the antioxidant defense genes named as SOD1 and SOD2. These enzymes serve a significant function in mitigating oxidative damage, and their regulation may be significantly influenced by epigenetic modifications, including DNA methylation. Objective This study aimed to investigate the promoter methylation status and expression levels of SOD1 and SOD2 genes in T2DM patients compared to healthy controls, to explore their potential as molecular biomarkers for T2DM. Methodology A total of 84 T2DM patients and 60 healthy controls were enrolled. Methylation-specific PCR (MSP) was applied to investigate the promoter methylation status of SOD1 and SOD2 genes, while real-time PCR was utilized to evaluate the expression levels of these genes in whole blood samples. Statistical analyses were performed to compare results between the T2DM group and the control group. Results The study revealed significant downregulation of both SOD1 and SOD2 gene expression in T2DM patients compared to controls, with p-values of 0.001 for both genes. Methylation analysis indicated increased promoter methylation of SOD2 in T2DM subjects, whereas SOD1 did not show any significant difference in the methylation status. Conclusion Our findings highlighted the critical role of reduced SOD1 and SOD2 expression in oxidative stress associated with T2DM. Although SOD2 downregulation was observed, the lack of significant differences in methylation frequency between patients and controls indicated that it may not serve as a definitive biomarker by itself. Therefore, the potential influence of methylation on SOD2 transcription warrants further investigation. Understanding these mechanisms could lead to novel therapeutic strategies targeting oxidative stress in diabetes management and at the same time improve our knowledge regarding the role of epigenetic factors in metabolic diseases.

Introduction: Metformin is a key treatment for type 2 diabetes, often linked to oxidative stress and genetic factors like GSTM1 and GSTT1 variations Methods: We studied 150 subjects, examining how their deletion polymorphisms in these genes correlate with Met treatment response. Those with GSTM1/T1 deletions (-/-) had a higher T2DM risk (2.71-fold, P=0.005). Results: Met responders with GSTM1(16bp) deletions had lower glucose levels compared to non-responders (P<0.0001), and similar trends were observed with GSTT1(54bp) deletions. Responders with both deletions also managed lipids better (P=0.0256; P=0.0151). Non-responders with GSTM1/T1 null genotypes had better HDL management (P=0.007). Conclusion: These findings suggested that GSTM1 deletion could predict T2DM susceptibility and Met response.

Background Several reports discussed a connection between CD36 genotypes associated with obesity, influencing the development of Type 2 diabetes mellitus (T2DM). Therefore, this study examines the prognostic value of CD36 polymorphism rs1761667 (G/A) in individuals with obese T2DM. The investigation also explores the correlation between this genetic variation and the clinical/biochemical parameters of the subjects. Methods Blood samples of a total of 475 subjects from north India were collected from the outpatient unit (OPD), Department of Medicine, KGMU, Lucknow as per inclusion/exclusion criteria. Anthropometric details of study subjects were recorded and biochemical parameters were estimated in 250 T2DM cases, 75 obese T2DM cases, and 150 controls. The CD36 gene variant rs1761667 (G/A) was subject to genotypic analysis using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, utilizing specific primers and HhaI enzyme. All statistical analysis was done using SPSS (ver. 21.0) and Prism (5.01) software. Results Fasting plasma glucose (FPG), systolic blood pressure (SBP), post-prandial glucose (PPG) were significant in T2DM subjects. Lipid profile such as Total Cholesterol (TC), Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) were also found significantly associated with obese T2DM cases. GA and AA genotypes of rs1761667 (G/A) showed significant associations in obese T2DM cases. The GA genotype demonstrated a considerable association ( P < 0.001) with a 2.77-fold increased susceptibility to the high risk of T2DM. The AA genotype was found to be significantly associated ( P = 0.008) with 2.94-fold higher risk of T2DM in obesity while 9.33 folds significant risk of developing obesity in T2DM cases. Conclusions The risk of obesity in T2DM cases can be assessed by genotyping the CD36 genetic variant rs1761667 (G/A). However, raised FPG, PPG, TC, LDL, and VLDL showed poor prognosis in obese T2DM cases. CD36 gene variant can be proposed as a prognostic biomarker for risk prediction of T2DM and obesity, while anthro-biochemical risk factors as preventive biomarker.

Coronavirus disease 2019 (COVID-19) is a disease that caused a global pandemic and is caused by infection of severe acute respiratory syndrome coronavirus 2 virus. It has affected over 768 million people worldwide, resulting in approximately 6900000 deaths. High-risk groups, identified by the Centers for Disease Control and Prevention, include individuals with conditions like type 2 diabetes mellitus (T2DM), obesity, chronic lung disease, serious heart conditions, and chronic kidney disease. Research indicates that those with T2DM face a heightened susceptibility to COVID-19 and increased mortality compared to non-diabetic individuals. Examining the renin-angiotensin system (RAS), a vital regulator of blood pressure and pulmonary stability, reveals the significance of the angiotensin-converting enzyme (ACE) and ACE2 enzymes. ACE converts angiotensin-I to the vasoconstrictor angiotensin-II, while ACE2 counters this by converting angiotensin-II to angiotensin 1-7, a vasodilator. Reduced ACE2 expression, common in diabetes, intensifies RAS activity, contributing to conditions like inflammation and fibrosis. Although ACE inhibitors and angiotensin receptor blockers can be therapeutically beneficial by increasing ACE2 levels, concerns arise regarding the potential elevation of ACE2 receptors on cell membranes, potentially facilitating COVID-19 entry. This review explored the role of the RAS/ACE2 mechanism in amplifying severe acute respiratory syndrome coronavirus 2 infection and associated complications in T2DM. Potential treatment strategies, including recombinant human ACE2 therapy, broad-spectrum antiviral drugs, and epigenetic signature detection, are discussed as promising avenues in the battle against this pandemic.

ObjectivesType 2 diabetes (T2D) imposes an enormous burden all over the world in both developed and developing countries. Inter-individual differences are attributed to polymorphisms in candidate genes resulting in altered absorption, transportation, distribution, and metabolism of oral antidiabetic drugs (OADs). Hence, the present study was undertaken to evaluate the pharmacogenetic impact of SLC22A1 gene variant rs628031 (G/A) on metformin monotherapy in newly diagnosed untreated T2D patients. MethodsNewly diagnosed T2D patients (n = 500) were enrolled according to inclusion/exclusion criteria. Initially, enrolled subjects were prescribed metformin monotherapy and followed up for at least 12 weeks. Response to metformin was evaluated in 478 patients who revisited for follow-up by measuring HbA1c. ResultOut of 478 patients, 373 were responders to metformin monotherapy while 105 were non-responders. The pharmacogenetic impact was evaluated by genotype, haplotype, and pharmacogenetic analyses. 'GG' genotype and 'G' allele of SLC22A1 rs628031 G/A were observed in 48.8% and 67.7% of Met responders, respectively, while 20.9% and 49.1 % were in non-responders. Therefore, there was a 2.18-fold increase in the success rate of Met therapeutics. ConclusionIndividuals carrying the 'GG' genotype or 'G' allele for SLC22A1 gene variant rs628031 G/A are better responders for Metformin monotherapy.

Cisplatin based chemoradiation (CRT) is the standard treatment for cervical cancer, which controls tumor growth and improves the overall survival of patients. However, patients undergoing chemo-radiation show widespread toxicities which may be either early or late. There is a constant effort to improve cancer therapy and overcome current challenges in cervical cancer by developing a combinatorial drug therapy using phytocompounds. In the present study, we review the combinatorial therapy of Cynodon dactylon and metformin with cisplatin as an alternative therapy for cervical cancer. During frequent exposures to chemotherapy, patients develop resistance to cisplatin, leading to cytotoxicity and recurrence. The conjugate of biologically active moieties of natural products along with cisplatin will probably lead to development of a new therapy with improved drug efficacy and reduced toxicity. Therefore, Cynodon dactylon (Doob) is a natural source of antioxidants and metformin which is an antidiabetic and has anticancerous properties too. The combinatorial regimen of Cynodon dactylon and metformin along with cisplatin may increase the drug efficacy and reduce cisplatin-related toxicity. However, widespread research is required in this field for the mainstream application of this combinatorial therapy.

Ever since its outbreak, Corona Virus Disease 2019(COVID-19) caused by SARS-CoV-2 has affected more than 26 million individuals in more than 200 countries. Although the mortality rate of COVID-19 is low, but several clinical studies showed, patients with diabetes mellitus (DM) or other major complication at high risk of COVID-19 and reported more severe disease and increased fatality. The angiotensin-converting-enzyme 2 (ACE2), a component of renin-angiotensin-system (RAS); acts on ACE/Ang-II/AT1recptor axis, and regulates pathological processes like hypertension, cardiac dysfunction, Acute Respiratory Distress Syndrome (ARDS) etc. The progression of T2DM and hypertension show decreased expression and activity of ACE2. There are several treatment strategies for controlling diabetes, hypertension, etc; like ACE2 gene therapies, endogenous ACE2 activators, human recombinant ACE2 (hrACE2), Angiotensin-II receptor blockers (ARBs) and ACE inhibitors (ACEi) medications. ACE2, the receptors for SARS-CoV2, facilitates virus entry inside host cell. Clinicians are using two classes of medications for the treatment of COVID-19; one targets the SARS-CoV-2-ACE2 interaction, while other targets human immune system. The aim of this review is to discuss the role of ACE2 in diabetes and in COVID-19 and to provide an analysis of data proposing harm and benefit of RAS inhibitor treatment in COVID-19 infection as well as showing no association whatsoever. This review also highlights some candidate vaccines which are undergoing clinical trials.