Purpose of Review The influence of gut microbiota on Type 2 Diabetes Mellitus (T2DM) is an emerging area of research. This review investigates the relationship between gut microbiota dysbiosis, bacterial translocation, and T2DM. It aims to elucidate how microbial imbalances contribute to the progression of T2DM through bacterial translocation and to evaluate dietary and therapeutic strategies to manage these effects. Recent Findings Recent studies highlight that dysbiosis in T2DM patients often leads to increased systemic inflammation, impaired glucose metabolism, and disrupted gut barrier integrity. These disruptions promote elevated levels of harmful bacterial components, such as lipopolysaccharides, in the bloodstream. This, in turn, is linked to worsening insulin resistance and metabolic dysfunction. Advances in molecular methods and biomarkers have provided deeper insights into bacterial translocation and its impact on diabetes. Dietary interventions, including nutraceutical agents, high-fiber and low-glycemic index diets, as well as the use of probiotics and prebiotics, have shown promise in restoring gut health and mitigating bacterial translocation. Conclusion Maintaining a balanced gut microbiota and intestinal barrier integrity is crucial for managing T2DM. Therapeutic strategies, including dietary modifications and nutraceuticals, have demonstrated potential in reducing bacterial translocation and systemic inflammation. Continued research is needed to refine these approaches and explore novel treatment modalities for improving metabolic health in T2DM patients.

Background: This 24-week randomized controlled trial aimed to evaluate the impact of multistrain probiotic supplementation on telomere length in patients with type 2 diabetes (T2DM). The study also assessed secondary outcomes including high-sensitivity C-reactive protein (hs-CRP) and glycated hemoglobin (HbA1c). Methods: A total of 124 participants with T2DM were randomly assigned to either a probiotic group (n = 62) or a placebo group (n = 62). Participants in the probiotic group consumed a supplement containing fourteen live microbial strains, including Lactobacillus plantarum, L. fermentum, L. acidophilus, L. casei, L. rhamnosus, L. reuteri, L. salivarius, L. paracasei, L. gasseri, Bifidobacterium bifidum, B. lactis, B. breve, Streptococcus thermophilus, and Saccharomyces boulardii, with each strain providing 2.148 billion CFUs per capsule, totaling 30 billion CFUs. The placebo group received vitamin B12 capsules without probiotics. The primary outcome was telomere length, and secondary outcomes included hs-CRP and HbA1c levels. Data were analyzed using intention-to-treat (ITT) and per-protocol (PP) methods. Results: The probiotic group exhibited a statistically significant decrease in telomere shortening compared to the placebo group (p < 0.001). The hs-CRP levels decreased more significantly in the probiotic group (p < 0.001), suggesting potential anti-inflammatory effects. The HbA1c levels improved in the probiotic group, with a reduction of 0.44% (p = 0.004). An age-stratified analysis revealed more substantial improvements in the 30–49 years cohort, which showed greater reductions in telomere shortening, inflammatory markers, and metabolic indicators compared to the 50–69 years group. Conclusions: Multistrain probiotic supplementation shows potential benefits in reducing telomere shortening and improving glycemic control. However, further long-term studies are needed to understand the underlying mechanisms and therapeutic implications of probiotics in T2DM. Trial registration: This trial was registered at the Clinical Trials Registry-India (CTRI/2023/07/055647).

BackgroundImeglimin, a novel oral hypoglycemic agent, is known to influence mitochondrial function and glucose metabolism. This study evaluates its effects on glycemic control, mitochondrial DNA (mtDNA) copy number, and telomere dynamics in type 2 diabetes mellitus (T2DM).MethodsType 2 diabetes mellitus patients were assigned to one of four treatment groups: (1) Imeglimin alone, (2) Imeglimin with metformin, (3) Imeglimin with other oral hypoglycemic agents, and (4) Metformin with other oral hypoglycemic agents. Clinical and metabolic parameters, mtDNA copy number, and relative telomere length were assessed at baseline and six months. Statistical analyses included paired t-tests and mixed models.ResultsThe study included participants with a mean age of 55.6 years (57% male, BMI 28.8 kg/m2). HbA1c significantly decreased in the Imeglimin + Other OHA (p < 0.001), Imeglimin + Metformin (p < 0.001), and Metformin + Other OHA (p < 0.001) groups, with a smaller but significant decrease in the Imeglimin monotherapy group (p = 0.04). mtDNA copy number increased significantly in the Imeglimin-based combination groups (p < 0.05) but not with monotherapy (p = 0.18). No serious adverse events were reported. Relative telomere length was only associated with age and changes in LDL-c levels.ConclusionImeglimin-based combination therapy effectively improves glycemic control and mitochondrial function, while monotherapy offers limited benefits. Combination therapy may be preferable for optimizing metabolic outcomes in T2DM. No significant change in telomere length was observed during the short period of time.

Background:Gestational Diabetes Mellitus (GDM) is a common pregnancy complication that poses risks to both mother and baby. Dietary management is crucial in controlling blood glucose, and recent evidence suggests that the order in which food is consumed (food sequencing) can improve glycemic control. Mobile health (mHealth) tools also offer promising support for healthier eating habits and glucose monitoring. This study evaluates whether combining a structured food sequence with mHealth monitoring enhances outcomes in women with GDM. Methods:Fifty-four pregnant women diagnosed with GDM were randomized into an intervention group (n = 27) and a control group (n = 27). The intervention group followed a structured food order-fiber first, then protein, and carbohydrates last-and tracked their intake using a mobile health application (JotForm). The control group received standard antenatal care without food sequencing. Fasting and postprandial glucose, lipid profiles, hemoglobin, and pregnancy outcomes were measured at baseline, the end of the third trimester, and 4 weeks postpartum. Data analysis included paired and independent t-tests or non-parametric equivalents, with chi-square tests for categorical variables. A p-value <0.05 was considered statistically significant. Results:The intervention group showed significant reductions in 1-h and 2-h postprandial blood glucose levels (-8.41 mg/dL and -7.56 mg/dL respectively, both p < 0.001), decreased LDL cholesterol (-7.33 mg/dL, p < 0.001), increased HDL cholesterol (+6.15 mg/dL, p < 0.001), and improved hemoglobin levels. They also had more normal deliveries (13 vs. 10) and fewer cases of shoulder dystocia (2 vs. 5) compared to controls. Additionally, this group exhibited lower average birth weights, fewer NICU admissions, and reduced neonatal complications. Conclusion:Combining a structured food sequencing approach with mHealth dietary monitoring improved maternal glycemic control and pregnancy outcomes in women with GDM. This strategy shows promise for supporting dietary adherence and managing GDM effectively, warranting further research to validate its broader application. Clinical trial registration:https://ctri.nic.in/Clinicaltrials/main1.php?EncHid=93509.81482, identifier CTRI/2024/01/061220.

Adipose tissue browning, the conversion of white adipose tissue (WAT) into brown or beige adipose tissue, offers potential for combating obesity and metabolic disorders. This review delves in to the transcriptional and epigenetic regulation of WAT browning and how it impacts metabolic health and its significance in various disease conditions. Further the review explains how various external factors such as diet and exercise play an influential role in the regulation of WAT browning. UCP1 gene, which plays a crucial role in cellular thermogenesis is found to be the major mediator of this phenomenon along with functional dynamics of mitochondria. Gut microbiome has been another focus point in this review that highlights how alterations to the composition of different species of bacteria in gut microbiome can directly influence WAT browning. Finally the review discusses the various pharmaceutical and neutraceutical options under research that targets WAT browning to improve metabolic status of an individual. Therapeutic strategies include β3-adrenergic receptor agonists, GLP-1 receptor agonists, AMPK activators, and natural compounds such as capsaicin and resveratrol. Emerging CRISPR/Cas9 gene therapies aim to induce WAT browning. Clinical evidence to prove the significance of this phenomena is currently limited but growing rapidly as seen in the number of clinical trials that are undergoing currently, therefore the review strongly rely upon animal model and cell culture based studies to justify this area of novel research. Despite its potential, challenges like individual variability, long-term safety, and complex gut microbiome interactions remain. Future research should target novel pathways, optimize therapeutic regimens, and personalize treatments.

Background: Mitochondrial dysfunction and metabolic stress play critical roles in type 2 diabetes mellitus (T2DM). This cross-sectional study examines the associations of mitochondrial DNA copy number (mtDNA-CN), fibroblast growth factor 21 (FGF21), and growth differentiation factor 15 (GDF15) with metabolic parameters, body composition, and physical performance in T2DM patients. Methods: A total of 181 T2DM patients (mean age: 53.0 years; 98 males, 82 females) were included in the study. Metabolic markers (HbA1c, lipid profile), body composition indices (skeletal muscle index [SMI], body fat percentage [PBF], and physical performance measures (handgrip strength, gait speed) were assessed. Serum mtDNA-CN, FGF21, and GDF15 levels were quantified, and their associations with clinical parameters were analyzed using correlation, regression, and receiver operating characteristic analyses. Results: Higher mtDNA-CN was associated with better glycemic control, lower triglycerides (TAG), and higher SMI (P < 0.001). Serum FGF21 correlated positively with PBF (P < 0.001) and TAG (P < 0.001), showing moderate predictive value for obesity. GDF15 was positively associated with BMI and PBF but had limited discriminatory power for glycemic control (area under the curve = 0.614). Both mtDNA-CN and GDF15 correlated with SMI, suggesting potential roles in muscle health. Conclusion: mtDNA-CN, FGF21, and GDF15 are linked to distinct aspects of metabolic and physical health in T2DM. mtDNA-CN reflects glycemic control and muscle health, FGF21 indicates metabolic disturbances in obesity, and GDF15 is associated with aging-related metabolic dysfunction. These biomarkers provide valuable insights into the interplay between mitochondrial function, metabolic health, and physical performance in T2DM.

This case highlights the occurrence of hand-foot syndrome due to the use of an antimetabolite group of drugs, capecitabine, which was used in the chemotherapy of a 56-year-old male patient who was diagnosed with rectosigmoid carcinoma. The patient was diagnosed with rectosigmoid carcinoma two months ago and underwent laparoscopic lower anterior resection and colorectal anastomosis. Subsequently, the patient commenced chemotherapy treatment with a combination of oxaliplatin and capecitabine. The patient presented to us with complaints of loose stools for the past three days, and discoloration of the palms, soles, and tongue was noted and subjected to a biopsy, which revealed features compatible with chronic, nonspecific dermatitis. The occurrence of such palmar-plantar erythrodysesthesia with capecitabine is yet to be extensively studied.

Background: Sodium-glucose cotransporter-2 inhibitors are an innovative diabetes treatment that lowers blood sugar levels without insulin. A growing body of evidence suggests that blood sugar levels are tightly correlated with uric acid levels in their blood and urine. To alleviate type 2 diabetes (T2DM) suffering, we tested dapagliflozin on serum and urinary uric acid levels of patients with T2DM and measured its efficacy in reducing uric acid levels. Methods: A study was conducted on 60 people with T2DM. Patients were treated with Dapagliflozin doses of 10 mg daily for 3 months. Three months later, we measured body weight, fasting, and post-prandial blood glucose levels, Hemoglobin A1C (HbA1c), serum lipids, renal function tests, routine urine, and serum uric acid. Results: A number of clinical parameters of T2DM patients were compared to those of healthy subjects of the same age group. A comprehensive analysis of all parameters was conducted to evaluate dapagli-flozin's impact. After 90 days of dapagliflozin treatment, serum uric acid levels dropped significantly from 9.0 to 8 mg/dL in the dapagliflozin group, as well as uric acid percentage in urine changed from 16.1 to 23.6 %. After three months of treatment, HbA1C levels decreased from 9.8 % to 8.5 %.Conclusion: Following treatment with dapagliflozin, the patients' Homeostatic Model Assessment for Insulin Resistance decreased to 4.0. Further, multivariate correlation analysis showed a correlation of serum uric acid with glycemic profile positively. In conclusion, dapagliflozin lowers uric acid levels and increases insulin sensitivity in diabetic patients to improve their glycemic control.(c) 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

BackgroundGestational diabetes mellitus (GDM) poses significant risks to both maternal and fetal health, including a heightened risk of developing type 2 diabetes (T2DM) in the future. Effective management often involves dietary changes, such as food-order, where vegetables are consumed first, followed by proteins, and then carbohydrates last. This study investigates whether food sequence improves glycemic control in women with GDM by slowing carbohydrate absorption, reducing glucose spikes, and enhancing insulin sensitivity.MethodsTwenty-five women with GDM participated in a four-week trial with three phases: baseline measurement (week 0), phase 1 (regular diet), and phase 2 (food-order) intervention. Primary outcomes were blood glucose and serum insulin levels, measured at fasting, 1-h, and 2-h postprandial intervals during each phase. In phase 1 (weeks 0–2), participants followed their usual diet. In phase 2 (weeks 2–4), the same participants followed a food-order regimen: vegetables first, then proteins, and carbohydrates last. Customized meal plans for vegetarians and non-vegetarians were provided. Participants were monitored via a mobile application (Jotform) for adherence. Follow-up blood glucose and insulin were measured before, and 60 and 120 min after, consuming a standardized meal (339 kcal, 16.4 g protein, 56.1 g carbohydrates, 3.4 g fat) in the clinic.ResultsThe food-order intervention resulted in a significant reduction in postprandial blood glucose by 5.87% (p = 0.001) at 60 min and 6.06% (p = 0.001) at 120 min. Also, Serum insulin levels decreased by 8.13% (p = 0.001) at 60 min and 11.10% (p = 0.001) at 120 min, compared to the regular diet. These results suggest improved metabolic control and insulin sensitivity.ConclusionPrioritizing vegetables before protein and carbohydrates improves glycemic control and insulin sensitivity in women with GDM. This simple strategy helps regulate blood glucose and may reduce the long-term risk of T2DM. It offers a practical approach to managing GDM, but further research with larger cohorts and longer interventions is needed to assess its long-term effects.Clinical trial registrationhttps://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=81473.12293, identifier CTRI/2024/01/061220.

This review explores the pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of diabetes and its complications, highlighting the therapeutic potential of various oral hypoglycemic drugs targeting this pathway. NLRP3 inflammasome activation, triggered by metabolic stressors like hyperglycemia, hyperlipidemia, and free fatty acids (FFAs), leads to the release of pro-inflammatory cytokines interleukin-1β and interleukin-18, driving insulin resistance, pancreatic β-cell dysfunction, and systemic inflammation. These processes contribute to diabetic complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases (CVD). Here we discuss the various transcriptional, epigenetic, and gut microbiome mediated regulation of NLRP3 activation in diabetes. Different classes of oral hypoglycemic drugs modulate NLRP3 inflammasome activity through various mechanisms: sulfonylureas inhibit NLRP3 activation and reduce inflammatory cytokine levels; sodium–glucose co-transporter 2 inhibitors (SGLT2i) suppress inflammasome activity by reducing oxidative stress and modulating intracellular signaling pathways; dipeptidyl peptidase-4 inhibitors mitigate inflammasome activation, protecting against renal and vascular complications; glucagon-like peptide-1 receptor agonists attenuate NLRP3 activity, reducing inflammation and improving metabolic outcomes; alpha-glucosidase inhibitors and thiazolidinediones exhibit anti-inflammatory properties by directly inhibiting NLRP3 activation. Agents that specifically target NLRP3 and inhibit their activation have been identified recently such as MCC950, Anakinra, CY-09, and many more. Targeting the NLRP3 inflammasome, thus, presents a promising strategy for managing diabetes and its complications, with oral hypoglycemic drugs offering dual benefits of glycemic control and inflammation reduction. Further research into the specific mechanisms and long-term effects of these drugs on NLRP3 inflammasome activity is warranted.

Background and objective Non-alcoholic fatty liver disease (NAFLD) is primarily perceived as a condition prevalent among obese individuals. Its pathogenesis is closely intertwined with metabolic syndrome components. However, the association between insulin resistance and NAFLD in nonobese individuals remains ambiguous. Observational studies have scrutinized the prevalence of insulin resistance and metabolic syndrome in lean NAFLD patients. Materials and methods This is an observational study, and NAFLD screening was carried out among inpatient and outpatient attendees at SRM Medical College's General Medicine Department. Out of 200 screened patients meeting inclusion and exclusion criteria, 80 were diagnosed with non-alcoholic fatty liver disease (NAFLD). The assessment of metabolic syndrome was performed using the NCEP-ATP III criteria, allowing for comparison between groups concerning insulin resistance and metabolic parameters. Results Among NAFLD patients, those in the obese age group exhibited a higher prevalence of hypertension (57.8%; p < 0.001) and metabolic syndrome (75.6%; p < 0.0001). The lean NAFLD group showed elevated HOMA-IR levels (4.16) compared to obese NAFLD patients (2.92), with a significant statistical disparity (p < 0.0001). Additionally, the HSI value significantly increased in obese NAFLD patients (p < 0.00001). Conclusion Insulin resistance, a key factor in metabolic syndrome, is prevalent in lean individuals with non-alcoholic fatty liver disease (NAFLD), playing a pivotal role in its development. This resistance, linked to metabolic syndrome, promotes hepatic triglyceride and fatty acid accumulation, leading to NAFLD. Moreover, insulin resistance correlates significantly with weight gain in NAFLD patients.

Diabetes mellitus (DM) patients have a higher incidence of musculoskeletal issues compared to those without diabetes. With diabetes-related complications increasing, early detection of musculoskeletal diseases is crucial for better quality of life and reduced morbidity. Limited joint mobility (LJM), also known as diabetic stiff hand or diabetic cheiroarthropathy (DCA), is an often overlooked complication of type 2 DM. It manifests as painless stiffness in hands, restricted joint movement, and tight skin. Contractures in hand joints can spread to major joints like elbows and knees, severely impacting daily tasks and quality of life. Physical examination aids in diagnosing LJM and related rheumatic conditions like scleroderma. The cause of DCA is unclear, but it involves nonenzymatic glycation of collagen, resulting in excess crosslinking and stiffening of joints. Diagnosis includes the "prayer sign" and "tabletop test." Studies link long-term diabetes and microvascular complications with LJM Syndrome. Cheiroarthropathy correlates with cardiovascular and cerebrovascular diseases. Hence, in this study, we undertook an assessment of the prevalence of cheiroarthropathy in type 2 DM patients with a view to determine its potential as a diagnostic marker for diabetic macrovascular complications. Therefore, an evaluation of DCA in individuals with DM across diverse age groups and varying duration of DM constituted the primary objective of this research endeavor. In the study on DCA, 251 type 2 DM patients aged 18–65 years were screened from inpatients and outpatients of SRM Medical College Hospital and Research Centre between February 2021 and July 2022. The SRM Institutional Ethical Committee approved the study (No. 2355/IEC/2021). Patients with certain conditions were excluded, and written informed consent was obtained. Before physical examination, data on patients' demographics, diabetes duration, treatment, and complications were collected. Weight, height, and body mass index were measured. Patients were taught the prayer sign and tabletop sign to assess DCA. Failure to touch fingers in the prayer stance or flatten the hand on a tabletop indicated LJM. Positive cases underwent further testing for rheumatoid arthritis and systemic sclerosis. The remaining patients were diagnosed with DCA. This comprehensive approach ensures accurate diagnosis and understanding of the condition's prevalence and impact in the study population. Data were presented as mean ± standard deviation, frequency, and percentage. The Pearson chi-square test compared categorical variables. The data were analyzed using IBM SPSS, version 21.0 (IBM Corp.). The study included 251 participants meeting criteria. DCA occurred in 46 (18.3%). No significant gender difference was observed (p > 0.05). Regarding age, 24.1% of those aged 51–60 years, 35.1% over 60 years, and 10.3% aged 41–50 years had DCA. Duration of DM varied: ≤5 years (8.0%), 6–10 years (26.1%), 11–15 years (29.5%), and >15 years (14.3%). Body mass index comparison showed no significant difference (p > 0.05): obese (24.4%), overweight (19.3%), and normal weight (10.3%) (Table 1). Treatment frequency and DCA correlation was statistically insignificant (p > 0.05). Cardiovascular disease correlated positively (p < 0.05) with DCA (46.7% with, 53.3% without). Cerebrovascular accidents showed statistically significant correlation (p < 0.05): 70.0% with and 30.0% without cheiroarthropathy. These findings provide insights into demographic and clinical factors associated with DCA. Out of 251 patients, 46 (18.3%) had DCA, aligning with reported prevalence ranges of 8% to 58% influenced by population, definition, and measurement methods.1 Distinguishing DCA from other hand issues like Dupuytren's contracture is crucial. Studies show DCA prevalence between 28.5% and 29.0%, with 22.6% reported in other research.2, 3 Our study found DCA prevalence increasing with age, consistent with prior findings linking DCA to aging. Analysis revealed a significant association between diabetes duration and DCA, indicating a higher risk with longer diabetes duration. Those with prepubertal onset of diabetes exhibited more severe joint mobility limitations, attributed to hyperglycemia-induced collagen deposition during growth spurts.4 Prolonged hyperglycemia leads to nonenzymatic collagen glycation, causing resistant collagen buildup and trapping of proteins, exacerbating extracellular matrix development. Oxidative stress and hyperglycemia trigger advanced glycation end products (AGEs), generating reactive oxygen species, and inflammatory responses, further damaging cells.5 Understanding these mechanisms sheds light on DCA pathogenesis and underscores the importance of glycemic control in diabetes management. In our study, we report 46.7% DCA patients with cardiovascular diseases similar to the findings by Einarson et al. in their study of prevalence of cardiovascular disease in type 2 DM.6 Similarly on comparing cerebrovascular accidents and DCA, 15.2% patients with cerebrovascular accidents had DCA. Both the results showed an increased prevalence of atherosclerosis leading to these macrovascular complications in DCA. Elevated glucose levels drive extracellular processes, leading to protein glycation and AGEs, contributing significantly to atherosclerosis development. AGEs activate endothelium, facilitate macrophage adherence, induce pro-inflammatory cytokine release, alter low-density lipoprotein particles, and disrupt extracellular matrix, exacerbating plaque formation and inflammation. Patients with DCA were found to have a higher prevalence of atherosclerosis leading to macrovascular complications. Therefore, better glycemic control of the patient is required in the presence of diabetic cheiroarthropathy to stop the progression of the disease and further deterioration of its complications. Athul Paul: Conceptualization, methodology, data curation, writing—original draft, visualization, investigation. Kothai Gnanamoorthy: Supervision, project administration, validation; Gisha Sivan: Data curation, writing—reviewing and editing, visualization, software; Janardanan S. Kumar: Supervision, project administration, validation. The authors would like to thank the management of SRM Medical College Hospital and Research Centre, SRM Institute of Science and Technology, Chennai, Tamil Nadu for providing facilities and encouragement. The authors declare no conflict of interest. None. All study procedures were approved by SRM Medical College Hospital and Research Centre Institutional Ethics Committee (No. 2355/IEC/2021).

INTRODUCTION:With newer anti-obesity medications (AOMs) being introduced at a rapid pace, it is prudent to make a concise and updated clinical practice document that may help busy clinicians in daily clinical practice. A group of metabolic physicians, diabetologists, endocrinologists, and bariatric surgeons assembled during the Integrated Diabetes and Endocrine Academy 2023 Congress (IDEACON, July 2023, Kolkata, India) to compile an update of pharmacotherapeutic options for managing people with obesity in India.AREAS COVERED:After an extensive review of the literature by experts in different domains, this update provides all available information on the management of obesity, with a special emphasis on both currently available and soon-to-be-available AOMs, in people with obesity.EXPERT OPINION:Several newer AOMs have been shown to reduce body weight significantly, thus poised to make a paradigm shift in the management of obesity. While the tolerability and key adverse events associated with these AOMs appear to be acceptable in randomized controlled trials, pharmacovigilance is vital in real-world settings, given the absence of sufficiently long-term studies. The easy availability and affordability of these drugs is another area of concern, especially in developing countries like India.

Hyperglycemia, a key characteristic of type 2 diabetes mellitus (T2DM), highlights the need for effective management strategies. This study aims to analyze the impact of multistrain probiotic supplementation on glycemic control in T2DM patients. During a 24-week randomized controlled trial involving 130 participants, subjects were assigned to either a probiotic group or a placebo group. The key outcomes included fasting blood glucose (FBG), postprandial blood glucose (PPBG), glycated hemoglobin (HbA1c) levels, and lipid profiles, assessed at baseline and post-intervention. The results indicated a significant reduction in HbA1c (p = 0.004) and increased HDL-c (p = 0.023) and improvements in lipid profiles in the probiotic group, alongside a trend toward decreased FBG and PPBG. No serious adverse effects were reported, indicating good tolerance of probiotics. These findings suggest that probiotics may positively influence metabolic parameters in T2DM patients, supporting their potential as a complementary dietary intervention. Further research is needed to understand the underlying mechanisms and enhance probiotic formulations for diabetic control.

Melioidosis is a rare disease caused by Burkholderia pseudomallei, , which has recently acquired prominence in India as an emerging pathogen. It is a gram-negative bacteria found in soil. As delayed diagnosis and treatment are linked to increased mortality, early diagnosis is crucial. We present here a unique instance of melioidosis that was made worse by a rare disorder known as hemophagocytic lymphohistiocytosis (HLH), which necessitates early treatment.

The mutualistic relationship between human health and gut microbiota has gained growing attention as a result of its far-reaching consequences. Diabetes medications, essential for managing type 2 diabetes, which regulate glucose metabolism, have shown effects that go beyond glycemic control by receiving attention for their possible influence on gut microbiota. Notably, metformin, a cornerstone therapy, has received a lot of attention for its ability to influence the gut microbiota. Metformin administration has been linked to changes in the abundance of specific bacterial taxa, including an uprise in beneficial microbes like Akkermansia muciniphila. These modifications have been linked to increased insulin sensitivity and better metabolic outcomes. Other classes of diabetes drugs, in addition to metformin, have shown potential effects on the gut microbiota. SGLT-2 inhibitors, for example, may contribute to changes in gut microbial communities, which could explain their cardiovascular and metabolic benefits. However, the processes underlying these interactions, are complicated and not entirely understood. Direct interactions between the gut microbiota and drug, changes in intestinal permeability, and modulation of bile acid metabolism are all possible mechanisms. Individual differences and genetic factors complicate the relationship even more. Understanding the intricate interplay between diabetes drugs and gut microbiota holds promise for developing personalized diabetes management approaches. Taking advantage of these interactions could lead to novel therapeutic strategies that improve drug efficacy and overall metabolic health. More studies are required to determine the exact mechanisms underlying these effects and to capitalize on their potential for improved patient outcomes. This review provides a concise overview of the effects of diabetes medications on gut microbiota composition and its importance.

Diabetes mellitus is a chronic metabolic condition marked by persistent hyperglycemia. It is a major issue of public health with wide-ranging effects. Telomeres are protective caps at chromosome ends, essential for preserving genomic stability and cellular integrity. Research highlights the complex link between diabetes and telomere biology and the potential interactions between the two. This review aims to present a summary of the relationship between diabetes and telomeres, highlighting significant discoveries and probable underlying mechanisms. Telomere shortening in those with diabetes and those at risk of getting the condition provides evidence that telomere dysfunction is linked to diabetes. It is said that telomere attrition, which is influenced by elements such as oxidative stress, inflammation, insulin resistance, and hyperglycemia, plays a major role in the pathophysiology of diabetes. Diabetes Mellitus's hallmark symptoms are chronic inflammation and oxidative stress, accelerating telomere shortening via pro-inflammatory cytokines production and reactive oxygen species, respectively. Telomere dysfunction is enhanced further by the long-term effects of insulin resistance and hyperglycemia. The onset of diabetic comorbidities such as cardiovascular disease, nephropathy, retinopathy, and neuropathy has also been linked to telomere shortening. Understanding how telomeres contribute to these issues may offer new therapeutic ideas. Diabetes and its consequences may be treated with telomere-targeted medicines, such as telomerase activators, telomerase gene therapy, and treatments that target telomere-associated proteins. However, more investigation is required to assess these strategies' security, effectiveness, and long-term impacts.

Dear Editor, In patients with T2DM, plasma lipoproteins abnormalities are observed due to impaired insulin action and highly elevated glycaemic parameters or directly due to metabolic disturbances induced by overweight.1 In 2006, the FDA approved the fat oxidation inhibitor Ranolazine to treat angina. Concerning Ranolazine's effect on diabetes, it is suggested that Ranolazine blocks late sodium channels (INa 1.3 isoform) channels in the pancreatic islet alpha-cells to decline Glucagon's liberation. Some studies, like low-dose streptozotocin-induced diabetes in mice, revealed its role in pancreatic beta-cell preservation by increasing ß-cell survival and improving glucose homoeostasis.2-4 Treatment with Ranolazine shown a consistent reduction in HbA1c levels in trials like the CARISA trial and Merlin TIMI 36 trial.5, 6 Ranolazine improves insulin secretion by inhibiting INa, IKr ion currents on subsist residuary beta-cells.7-9 There are no clinical trials available that portray the action of Ranolazine on diabetic dyslipidaemia as previous studies have only shown a Ranolazine effect on glycaemic parameters. This study compares the efficacy of standard therapy and Ranolazine add-on therapy in improving lipid and glycaemic parameters in patients with diabetic dyslipidaemia (Figure 1). This randomised observational study recruited (n = 89) newly documented diabetic patients of either sex with an age group of 18-80years, HbA1c 6%-8%, abnormal lipid profile, along with/out other comorbidities (CAD, hypothyroidism), BMI ≥ 25kg/m2. Moreover, this study excludes subjects with a history of antidiabetic or lipid-lowering therapy, CKD patients, pregnancy and lactating women. Based on computer-generated random allocation, these subjects (82) were allocated to group A (41 received standard therapy) and group B (41 received Ranolazine 500 mg BD with the standard therapy). The patients were observed for two follow-ups (6 months). The glycaemic and lipid parameters were collected from each group every third month until 6 months and measured using Beckham 480 auto analyser. We ascertained the difference between the groups using two-way ANOVA analysis. Our study revealed that Ranolazine add-on with standard therapy shown much-improved efficacy in reducing FBS (P < .001), PPBS (P < .001), HbA1c (P < .05), Fasting Insulin (P < .001), TC (P < .001), TG (P < .001), and LDL (P < .001). In contrast, standard therapy showed improved efficacy only in FBS (P < .01) and PPBS (P < .01) after two follow-ups. Metabolic deregulation due to insulin resistance is most common in diabetes dyslipidaemia. In support of this hypothesis, our study would add Ranolazine's impact on reducing insulin resistance as a sign of improving the condition. Compared to the existing Ranolazine trials on diabetes, this study would add to its effect on dyslipidaemia. In conclusion, Ranolazine addition to the standard therapy would provide an additional benefit in reducing diabetes progression and dyslipidaemia. The present study suggests that Ranolazine add-on therapy with standard therapy would offer a broad spectrum of treatment in diabetic dyslipidaemia patients. The authors have no conflict of interest to declare. The clearance for this trial was approved by the Institutional human ethical committee (1685/IEC/25/04/2019). The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

•Ranolazine showed significant efficacy by reducing glycemic parameters in diabetic dyslipidemia patients.•β – cell function and insulin sensitivity increased in ranolazine treatment group.•Significant reduction in the triglycerides was observed in the ranolazine treatment when compared to standard.

Introduction:Serum ferritin, a marker of iron stores has been implicated to play a role in many acute and chronic disease conditions. Several epidemiological studies have reported excess deposition of iron in tissues related to insulin resistance (IR). Aim & Objective:The aim of this study is to investigate the risk of iron stores as assessed by serum ferritin to see where it could be an early indicator of insulin resistance in Pre-diabetes. Material and Methods:This case control study included a total of 224 participants with 112 Pre-Diabetic individuals who attended the OP Department of General Medicine and matchedwith 112 normal healthy individuals who attended the Master health checkup OP in SRM MCH & RC. Their fasting blood samples were collected to estimate FBS, PPBS, Iron, Ferritin and Insulin. Insulin resistance was calculated using homeostasis model assessment insulin resistance (HOMA-IR) formula. Statistical analysis was performed by bivariate correlation and paired samples t test between cases and controlsby SPSS IBM social software. Results:Serum Ferritin (110.39 ± 13.52), Iron (113.32 ± 14.81), %TS (32.18 ± 6.24), Serum Insulin (17.04 ± 1.89) and HOMA-IR (4.98 ± 0.77) were significantly high in Pre-Diabetics when compared with controls Serum Ferritin (43.46 ± 9.26), Iron (70.02 ± 6.79), %TS (18.79 ± 3.04), Serum Insulin (8.02 ± 1.86) and HOMA-IR (1.71 ± 0.59). Similarly we found a significant positive correlation between Ferritin and Insulin (r = .956**, P =