Background: The renin–angiotensin–aldosterone system (RAAS) is important in regulating blood pressure and electrolyte balance. The main effector hormone of the RAAS is angiotensin II, which is generated from angiotensin I in the circulation and in the tissues, mostly as a result of the action of angiotensin-converting enzyme (ACE). The ACE gene has received substantial attention in recent years as a candidate gene for a variety of diseases. Objective: This study was conducted to determine the association of insertion/deletion (I/D) polymorphism of ACE gene in type 2 diabetes mellitus (T2DM), hypertension (HT), and chronic kidney disease (CKD) subjects among South Indian regional population. Methods: A total of 105 subjects participated in this study including 30 T2DM (Group 1), 30 HT (Group 2), 35 CKD (Group 3) patients and 10 controls (Group 4). Blood samples were collected and biochemical investigations were done. Polymerase chain reaction amplification was performed to genotype the DNA. The distribution and allelic frequency of I/D (rs1799752) polymorphism at the 287-base pair Alu repeat sequence in the intron 16 of ACE gene were analyzed using specific primers. Results: The ACE genotypes were distributed as II, 17%; DD, 47%; and ID, 37% in the T2DM group; II, 10%; DD, 50%; and ID, 40% in the HT group; II, 17%; DD, 54%; and ID, 29% in the CKD group; and II, 50%; DD, 20%, and ID, 30% in the control group. The frequency of DD genotype was significantly higher in HT (P = 0.05) and CKD patients (P = 0.05) compared to controls. In codominant model analysis, DD genotype versus II genotype was associated with increased risk of T2DM (odds ratio [OR] = 4.37; 95% confidence interval [CI] = 1.31–14.504), HT (OR = 9.0; 95% CI = 2.23–36.17), and/or CKD (OR = 5.73; 95% CI = 1.906–17.282), respectively. The D allele was more frequent in T2DM (65%), HT (70%), and CKD patients (69%) compared to controls (35%) (P = 0.018, P = 0.005, and P = 0.006, respectively). The D allele was associated with increased risk of T2DM (OR = 3.44; 95% CI = 1.19–9.96), HT (OR = 4.33; 95% CI = 1.48–12.65), and CKD (OR = 4.05; 95% CI = 1.42–11.55). Conclusion: The DD genotype and the D allele of the ACE I/D gene polymorphism can be a risk factor for T2DM, HT, and CKD in South Indian regional population. This result suggests that T2DM and HT patients should be offered analysis to identify defects in ACE I/D polymorphism, which might help to determine the course of CKD disease and aid to choose appropriate antihypertensive therapy with ACE inhibitor/angiotensin receptor blockers.

Background: In India, glimepiride has become a promising option for add-on therapy with metformin in patients with type-2 diabetes mellitus (T2DM) owing to its efficacy, safety, and cost-effectiveness. This study aimed to analyze the clinical utility of multiple strengths of glimepiride and metformin fixed-dose combination (FDC) in obese/overweight patients with T2DM. Methods: This case-based questionnaire survey was conducted between June 2020 and June 2021 and included health-care professionals across India to assess the usage pattern of glimepiride and metformin FDC. Results: Overall, data from 1345 patients taking multiple strengths of glimepiride and metformin FDC were analyzed, of which 64.7% were men. A total of 57.6% of patients were overweight, 29.4% were obese Class I, 9.6% were obese Class II, and 3.4% belonged to obese Class III. Sedentary lifestyle (60.3%), smoking (36.7%), and emotional stress (33.3%) were the most common risk factors. Among the available strengths, glimepiride 2 mg and metformin 500/850/1000 mg FDC was most widely used in 50.5% and 47.4% of patients from overweight and obese groups, respectively. A total of 90.3% and 89.1% of patients, respectively, from the overweight and obese groups did not observe weight gain. The majority of the patients from overweight and obese groups observed blood pressure within optimum levels (68.5% and 71.4%, respectively). The mean glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose levels were significantly reduced with posttreatment of glimepiride and metformin FDC with a mean change of 1.4%, 44.3 mg/dL, and 73.5 mg/dL, respectively (P < 0.01). The physician global evaluation of efficacy (90.3%) and tolerability (91.1%) showed the majority of the patients on a good to excellent scale. Conclusion: The real-world evidence in the Indian clinical setting indicates that the glimepiride and metformin FDC was found to be effective in achieving glycemic control and it is observed to be safer in terms of weight gain and hypoglycemia.

Background: There is an increasing need to revise diabetes management. Two-thirds of patients with diabetes do not have their blood sugar under control. There has been increasing evidence suggesting the positive impact of diet and lifestyle on blood sugar control. This study aims to demonstrate the adoption of the Glucose Level-Assisted Monitoring Diet (GLAM diet) validated by the aid of ambulatory glucose profiling and examine the impact of the GLAM diet on blood glucose concentration, lipid profile, and glucose variability. Methods: In this open-label, interventional pilot study, we enrolled 50 diabetes patients with or without hypertension to receive a GLAM diet, in addition to counseling. The primary outcome was the control and remission of diabetes. The secondary outcome was a composite of optimal maintenance of glucose concentration, optimal lipid profile, glucose variability evaluation, reduced insulin supplementation, diabetes-related complications following the GLAM diet, lifestyle modification, and overall quality of life through indicators such as sleep, stress, and nutrition. Results: GLAM diet significantly reduced Fasting Blood Sugar (FBS) (202 ± 65.47 mg/dL vs. 160.2 ± 37.75 mg/dL, P < 0.001), postprandial blood sugar (PPBS) (246.1 ± 74.74 mg/dL vs. 196.5 ± 45.48 mg/dL, P < 0.001), laboratory glycated-hemoglobin (9.2 ± 1.74% vs. 8.1 ± 1.5%, P < 0.001), and average glucose (182.4 ± 47.54 mg/dL vs. 152.2 ± 39.32 mg/dL, P < 0.001). The glucose remained within target increasing frequently after the diet was implemented (49.7 ± 27.11% vs. 65.6 ± 20.01%, P < 0.001) and although fell just short of statistical significance, there was a percentage decrease in glucose level above target (46.6 ± 29.17% vs. 27.6 ± 22.71%, P = 0.109) observed in the study group. Patients also experienced significantly reduced body weight, body mass index, waist circumference, hip circumference, body fat percentage, and Mean amplitude of glycemic excursions (MAGE), Continuous overall net glycemic action (CONGA), and standard deviation values in comparison to baseline. Conclusion: Patients initiated onto the GLAM diet had better glycemic control, lipid profile, and glucose variability along with enhanced sleep, reduced stress, and improved nutrition understanding in study participants. In conclusion, the GLAM diet apart from reducing glycemic burden also helped to improve the overall quality of life.

Iatrogenic hypoglycemia is the most feared and common complication of insulin therapy. Hypoglycemia can have serious consequences and can be potentially life-threatening. In addition to the neurological manifestations of severe hypoglycemia, hypoglycemia may be associated with cognitive dysfunction, cardiovascular events, arrhythmias, and increased mortality. Recurrent episodes of hypoglycemia may lead to hypoglycemia unawareness, which increases the risk of severe hypoglycemia. Therefore, prevention of hypoglycemia remains a priority in persons with diabetes on insulin therapy. The “THINK” strategy provides a comprehensive approach for diabetes care providers to minimize the risk of hypoglycemia related to insulin therapy by mitigating factors that increase the risk. This requires setting reasonable glycemic Targets keeping in mind a person's risk of hypoglycemia; choosing the right Tools such as insulin formulation and regimen with lower risk and adequate glucose monitoring; judicious Titration of insulin doses; use of modern Technology such as continuous glucose monitoring, continuous subcutaneous insulin infusion, and sensor augmented pumps in patients at high risk; maintaining Harmony between insulin dose, diet, physical activity, and changes in lifestyle; Individualization of diabetes therapy; ensuring there are No errors in insulin administration; and empowering patients with Knowledge about hypoglycemia. The THINK strategy offers a handy tool for tailoring insulin therapy to minimize hypoglycemia risk.

Obesity is a chronic metabolic disease affecting individuals all over the world and is known to be a main risk factor for type 2 diabetes (T2D). In countries like India, T2D occurs with a lower degree of obesity as compared to T2D in western countries. It is important to tackle obesity in T2D because studies have shown that modest weight loss leads to improvements in glycemic levels, thereby reducing the risk of diabetes-related complications and comorbidities. Obesity complicates the management of diabetes, particularly the goal of achieving tight glycemic control as it is associated with insulin resistance. In this article, we are going to discuss choice of therapies in the management of T2D in obese individuals. In patients with T2D and obesity treatment approach should be individualized and it includes intensive lifestyle intervention, pharmacologic therapy, and/or metabolic surgery. Additional attention should be given to concomitant therapies for other comorbidities which may further lead to weight gain. Considering the strong link between obesity and T2D, the first choice of therapy after lifestyle modification should be glucose-lowering agents, which promote weight reduction or are at least weight neutral. Metformin, alpha-glucosidase inhibitor, sodium-glucose co-transporter 2 (SGLT-2) inhibitor, glucagon-like peptide–1 receptor agonist (GLP-1 RA), and amylin mimetic promote weight loss along with additional cardiovascular benefits of GLP-1 RA, SGLT-2 inhibitor, and improved renal outcomes with SGLT-2 inhibitor. Weight neutral therapies include dipeptidyl peptidase-4 inhibitors and fixed ratio insulin/GLP-1 RA combination therapies (insulin degludec/liraglutide, insulin glargine and lixisenatide) can also be considered as they help to limit weight gain. Therapies such as thiazolidinedione, insulin secretagogue (sulfonylurea and meglitinide), and insulin are less suitable for individuals with obesity and T2D as they are associated with weight gain.

Painful diabetic peripheral neuropathy (PDPN) is a commonly encountered problem by a physician and poses a major treatment challenge. Although poor glycemic control is considered to be a main cause for the development of peripheral neuropathy, the overall etiopathogenesis remains unclear and needs further research. There are various tools to assess the status of nerves, but PDPN being a subjective factor is often measured in terms of pain scores or pain scale looking at the intensity and the phenotype of pain. PDPN affects the individual's quality of life and daily living and often disturbs the sleep and mental health. The management of PDPN includes achieving good glycemic control, following foot care practices, including the use of appropriate footwear and treatment for pain relief. The treatment of choice varies from topical application to the pain relieving patches and use of drugs such as anticonvulsants, antidepressants, and opioids which have shown some beneficial effect. Interventional and regional anesthesia have also been tried for the treatment of PDPN. Surgical decompression has shown a favorable effect on pain relief. There are unmet needs in the therapeutic management of PDPN, as available drugs give acceptable pain relief in very few patients, and fear of side effects may limit full-dose treatment. Till date, no medicine is available to reverse neuropathy.

Infectious diseases are more common and severe in diabetes. Diabetes predisposes to various infections through alterations in innate and acquired immune defences. Outcomes of infection are worse in people with uncontrolled glycemia, including an increased mortality. The infections can affect all organs and all systems. In patients with diabetes, the infections can be broadly classified into two categories. Infections that are common in the general population have more severe clinical presentation and worse outcomes among patients with diabetes. The second group is of infections that are peculiar to patients with diabetes, being virtually rare in the normal population, such as foot infections, malignant external otitis, rhinocerebral mucormycosis, emphysematous pyelonephritis and gangrenous cholecystitis, etc. Epidemiological data on the true incidence of atypical and rare infections are scarce. This review will highlight the prevalence, consequences, severity, and pattern of infections in the population with diabetes in India. This review of epidemiological prevalence may guide the clinicians for early suspicion, identification of infectious disease, and right selection of the antimicrobial agents which may lead to a better outcome.

The chronic low-grade inflammation in obesity and multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of various rheumatic autoimmune and inflammatory conditions. Obesity is a low-grade systemic inflammatory condition with elevated levels of inflammatory markers such as leptin, C-reactive protein, tumor necrosis factor-α, and interleukin-6. Dysregulation of the cytokines and adipokines is a feature of metabolic syndrome, suggesting a complex relationship between autoimmunity, obesity, and atherosclerosis. We discuss the effects of obesity and its association with newly diagnosed immune-mediated disorders such as Sjogren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and antiphospholipid antibody syndrome in a case series of eight patients.