Sambit Das

Noncollinear (NC) magnetism and spin-orbit coupling (SOC) are indispensable for predictive ab initio materials simulations with pronounced relativistic effects and magnetic frustration, yet they significantly increase the cost of cubic-scaling density functional theory (DFT) by introducing complex 2-component wavefunctions per electron and consequently much larger eigenproblems. We present a GPU-centric high-performance framework for NC-SOC DFT that combines: (i) algorithmic advances for solving finite-element (FE) discretized DFT equations; (ii) residual-based Chebyshev filtered subspace iteration (R-ChFSI), tolerant to inexact matrix-vector products, for the resulting sparse generalized eigenproblem; (iii) a matrix-free strategy for accelerating FE Poisson solver; (iv) R-ChFSI-enabled mixed-precision computation with block floating-point compressed MPI communication at compression ratios over 4x, preserving double-precision robustness while reducing compute and data movement costs; and (v) a communication efficient band-partitioning algorithm to improve scalability. Numerical results demonstrate improved time-to-solution and excellent scaling on exascale architectures, enabling fully relativistic pseudopotential DFT simulations of up to 100,000 electrons.

Noncollinear (NC) magnetism and spin-orbit coupling (SOC) are indispensable for predictive ab initio materials simulations with pronounced relativistic effects and magnetic frustration, yet they significantly increase the cost of cubic-scaling density functional theory (DFT) by introducing complex 2-component wavefunctions per electron and consequently much larger eigenproblems. We present a GPU-centric high-performance framework for NC-SOC DFT that combines: (i) algorithmic advances for solving finite-element (FE) discretized DFT equations; (ii) residual-based Chebyshev filtered subspace iteration (R-ChFSI), tolerant to inexact matrix-vector products, for the resulting sparse generalized eigenproblem; (iii) a matrix-free strategy for accelerating FE Poisson solver; (iv) R-ChFSI-enabled mixed-precision computation with block floating-point compressed MPI communication at compression ratios over 4x, preserving double-precision robustness while reducing compute and data movement costs; and (v) a communication efficient band-partitioning algorithm to improve scalability. Numerical results demonstrate improved time-to-solution and excellent scaling on exascale architectures, enabling fully relativistic pseudopotential DFT simulations of up to 100,000 electrons.

Magnesium is the lightest structural alloy, yet its practical use is limited by its low ductility. Recent studies suggest ductility enhancement in dilute Mg alloys may stem from favorable solute modification ofpyramidal I/II screw dislocation core energy difference, activatingslip via a double cross-slip mechanism. This work conducts large-scale DFT calculations, reaching ~6,000 atoms, ofdislocation energetics in Mg and Mg-Y/Zn alloys. We find that relative solute strengthening effects on pyramidal I and II screw dislocation glide are crucial for cross-slip enhancement in Mg-Y, in contrast to prior investigations, that find solute-mediated dislocation-core energy modification as the main driver. Our predictions align with single- and poly-crystal experimental results and also capture the transition from pyramidal II to I preferred slip in Mg-Y.

Artifacts for the SC26 submission titled "Towards exascale fully relativistic pseudopotential density functional theory calculations enabled by mixed-precision computation and compressed-communication using residual based subspace iteration"

Artifacts for the SC26 submission titled "Towards exascale fully relativistic pseudopotential density functional theory calculations enabled by mixed-precision computation and compressed-communication using residual based subspace iteration"

This opinion piece reviews the history of malnutrition related, or malnutrition modulated diabetes mellitus (MMDM). It reviews various terms used to describe this condition, and analyzes current efforts at renaming it as type 5 diabetes. It provides a simple, yet effective diagnostic checklist, based upon Ahuja's diagnostic criteria, for MMDM. While research is certainly required to define and describe this entity, renaming it will create confusion and chaos, rather than comprehension or clarity.

Pituitary apoplexy (PA) is a rare but potentially life-threatening endocrine emergency, typically resulting from sudden-onset haemorrhage within the pituitary gland. If not promptly diagnosed and managed, it can lead to severe hormonal disturbances and neuro-ophthalmic complications with fatal consequences. Early recognition is crucial for improving patient outcomes. Certain conditions increase susceptibility to PA, including pre-existing pituitary adenomas (most commonly non-functioning), the postpartum period, diabetes mellitus, hypertension, sickle cell anaemia, and acute shock. Here, we describe five cases of PA, each with varied signs and symptoms, which underscores the clinical heterogeneity with which pituitary apoplexies can present. The first and second patients exhibited significant pituitary dysfunction and hyponatremia, necessitating steroid replacement and supportive care, leading to gradual recovery. The third patient presented with an incidental MRI finding of pituitary haemorrhage and remained hemodynamically stable without any evidence of hypopituitarism. The fourth case presented with cranial nerve palsies, while the fifth case, which presented as a prolactinoma, had apoplexy after starting cabergoline therapy. A high index of suspicion is essential for timely diagnosis. Emergency magnetic resonance imaging (MRI) of the sellar region is the gold standard for confirming the diagnosis. Rapid intervention, including appropriate hormonal replacement and neurosurgical evaluation, can be life-saving. This case series highlights the diverse clinical presentations of PA and outlines a structured approach to its management.

PURPOSE OF REVIEW: Given the global rise of MASLD, which impacts approximately one-third of the population, there is a need for earlier diagnosis and effective treatment strategies to avoid long-term hepatic cardiovascular and renal complications. This review summarizes the recent advances in noninvasive diagnosis and new pharmacological agents approved for MASLD. RECENT FINDINGS: The main step forward in diagnostics is a step away from invasive biopsy and emphasis on noninvasive methods including serum biomarkers (e.g. CK-18 and FGF21), imaging (e.g. MRI-PDFF and US-FLI), combination of the two and use of artificial intelligence and machine learning models, for early detection and risk stratification of MASLD and MASH. Multiomics approaches, such as metabolomics and lipidomics, reveal disease-specific signatures, and may help with phenotypic classification of MASLD. Personalized management for MASLD include gut microbiota modulation and point-of-care devices for rapid diagnosis. Novel therapies include THR β agonists, GLP-1/dual GLP-1/GIP agonists, FXR agonists and FGF analogues, which show promise in reducing hepatic fat and fibrosis. SUMMARY: These findings enable earlier MASLD diagnosis and tailored interventions, improving clinical outcomes in primary care and resource-limited settings. Future research should focus on validating cost-effective tools, and developing combination therapies to address the multifaceted nature of MASLD.

Background Fixed-dose combinations (FDCs) of antidiabetic agents offer improved compliance and metabolic control in real-world settings. Objectives The present study assessed the effectiveness and safety of early initiation of an FDC of dapagliflozin and sitagliptin in Indian patients with type 2 diabetes mellitus (T2DM) and associated cardiometabolic comorbidities. Methodology This retrospective, observational study included patients aged 18-59 years with T2DM, baseline BMI ≥25 kg/m², HbA1c levels between 7.0% and 10.5%, and prescribed the FDC of dapagliflozin and sitagliptin across five Indian centers. Effectiveness outcomes included changes in glycemic profile, renal function, body weight, BMI, serum triglycerides (TGs), and blood pressure (BP). Results A total of 250 patients were included, with a mean age of 46.9 years, predominantly male. The mean waist circumference of 94.6 cm indicated central adiposity. Dyslipidemia and hypertension were the most common comorbidities. A significant reduction in glycated hemoglobin (HbA1c) was observed (-1.1%, p<0.001). Improvements in fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) were statistically significant. Patients with dyslipidemia or hypertension also experienced significant reductions. The study further demonstrated significant improvements in renal parameters. Body weight and BP were significantly reduced with this FDC. No adverse events were reported. Conclusion Early initiation of an FDC of dapagliflozin and sitagliptin led to significant improvements in glycemic, renal, and cardiovascular parameters in patients with T2DM. Its favorable effectiveness and safety profile, even among those with common comorbidities such as hypertension and dyslipidemia, underscore its potential as a comprehensive treatment option in routine clinical practice.

Background Metabolic disorders, including diabetes mellitus (DM), diabetic dyslipidemia (DD), and metabolic-dysfunction-associated steatotic liver disease (MASLD), are significant health challenges in India. This study aims to evaluate the real-world effectiveness and tolerability of saroglitazar (4mg) in Indian adults with type 2 diabetes mellitus (T2DM), DD, and MASLD, focusing on changes in glycemic, lipid, and hepatic biomarkers. Methods This retrospective study included adult patients with metabolic diseases (≥ 18 years) who were prescribed saroglitazar (4 mg) at baseline and continued therapy at least till the next follow-up visit after 90 days. The patients with at least one follow-up visit after 90 days from baseline with values for glycemic parameters, lipid parameters, aspartate transaminase (AST), and alanine transaminase (ALT) available at both visits were included. Changes in glycemic parameters, lipid profile, and liver enzymes were assessed from baseline to the follow-up visit. Disease conditions, concomitant medications at baseline, and adverse events at the follow-up visit were also evaluated. Results A total of 553 patients were included in this study. The most common conditions at baseline were DM, dyslipidemia, and hypertension. Saroglitazar significantly improved glycemic control, reducing glycosylated hemoglobin (HbA1c) by -0.71% from baseline to the follow-up visit. Fasting blood glucose (FBG) and postprandial blood glucose (PPBG) in the overall patient population decreased by -21.24 mg/dL (n =410) and -24.28 mg/dL (n = 178), respectively. In patients with baseline FBG >100 mg/dL (n = 358), the FBG reduction was -26.46 mg/dL, while in patients with PPBG >140 mg/dL (n = 151), the PPBG reduction was -31.73 mg/dL. There was a substantial improvement in the lipid profile, including a significant reduction in serum triglycerides (TG) (-55.41 mg/dL) and LDL (-6.95 mg/dL). Hepatic parameters improved, with AST and ALT decreasing by -2.62 IU/L and -7.95 IU/L, respectively. No significant adverse events and renal impairment were observed. Conclusion Saroglitazar demonstrated significant improvements in glycemic control, lipid profile, and liver enzymes with a favorable safety profile in Indian patients with metabolic diseases.

INTRODUCTION The previous endocrine society of India clinical practice recommendations were published in 2022, however a lot of developments have occurred in the obesity space in the Indian setting following that.[1,2] From more recent clinical studies in the Indian population to newer approvals, availability and reduced cost for some of the anti-obesity medications, led to the need to develop this document. While the previous document was exhaustive, the four key domains that were identified as key areas, where an update is required included the fast-changing epidemiology of obesity, a summary of the pharmacological options, the associated medication counselling, and the novel concepts in the psycho-social aspects of obesity management. SECTION A – FAST CHANGING EPIDEMIOLOGY OF INDIAN OBESITY Obesity has reached pandemic proportions globally, and the prevalence is rapidly increasing even in developing countries like India. Obesity is defined as presence of excessive fat in the body that leads to an increased risk of adverse health outcome. This excessive fat could be present either globally, in specific regions of the body or in organs as ectopic lipids.[3] Globally, approximately 650 million adult people and about 340 million children and adolescence between the age of 5 to 19 years, live with obesity and these numbers are rapidly increasing.[4] As per the most recent data published from the United States, using the National Health and Nutrition Examination Survey about 42.4% of adults have a body mass index of more than equal to 30 kg/m2 and 20.9% of children have a ≥95th age and gender matched BMI percentile.[5] The World Obesity Federation now provides a national obesity risk for each country. This represents a composite score based on the obesity prevalence, rate of increase and indicators of treatment. India has been given a score of 7 out of 10. In the recently published, The Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study, which is a nationwide cross-sectional population-based survey among individuals above the age of aged 20 years from urban and rural areas across 31 states and Union territories of the country.[6] Generalized and abdominal obesity was defined as per the WHO Asia Pacific guidelines. A whopping number of estimated 254 million people with generalized obesity (28.6%) and 351 million individuals with abdominal obesity (39.5%) were found in this study. The state with the highest rates of abdominal and generalized obesity was Puducherry (53.3% and 61.2%) and that with the lowest rates was Jharkhand (11.6% and 18.4%). Furthermore, the urban population in these states was found to have a prevalence of more than 25%.[3] Obesity data from India across the life span Obesity in Indian children Child hood obesity has shown a rising trend over the last few decades. Initial studies in India done from Delhi,[7-10] Chandigarh,[11] Chennai,[12] Pune,[13] and West Bengal,[14] have shown the prevalence of childhood obesity around 10%–12% and overweight around 12%–22%. More recent literature, however has shown a significantly higher prevalence of obesity approaching in up to 30% of patients.[15-17] Obesity in young adults among the Indian population In another study, conducted among 647,168 women with a median age of about 30 years the prevalence of overweight women was 22.6% and that of women with obesity was 10.7%. Older women, those who were married, had previous history of pregnancy, were highly educated, wealthy, and living in urban regions had higher prevalence and odds of having overweight/obesity.[18] This has been further corroborated from the data obtained through the national family health surveys that have shown a prevalence of overweight and obesity between 35% to 40%.[19] Obesity in the older population in India In a recent study by Singhania et al.,[20] the prevalence of overweight and obesity in rural middle aged postmenopausal women in North India was found to be about 35.5%. In another study among rural south Indian women, predominantly farmers with a mean age of about 60 years, about two thirds of the study population was found to have body mass index (BMI) in obese range.[21] A recent paper by Verma et al.[22] analysing the prevalence of obesity through the Longitudinal Ageing Study in India found the prevalence to be 27% in 72,250 older adults. Prevalence of the unique South Asian thin-fat obesity The South Asian ethnicity is known to have a predisposition to develop obesity related complications at a lower body mass index.[23,24] This was first shown in the famous paper called the YY Paradox and has thus been validated in several studies by different names like the normal weight obesity, metabolic obesity, skinny fat and thin-fat phenotype.[25] The prevalence of this phenotype has been about 15% in Chennai and about 16% in Mumbai.[26,27] In another recent study by Kapoor et al.[28] from Kerala the prevalence of normal weight obesity among the high diabetes risk individuals was found to be about 30 percent of the population. They were also found to have a significantly higher prevalence of diabetes, hypertension and dyslipidaemia as compared to non-obese, normal fat containing individuals and were resistant to change following a life style intervention.[28,29] Concordance with the Lancet Commission on obesity The ESI guidelines are concordant with the philosophy expressed by the Lancet Commission on obesity.[30] In fact, in many ways, the ESI’s statements ante-date, and amplify, the message shared by the Commission. The multifactorial etiopathogenesis of obesity, and the varied clinical presentations of the disease, are clearly mentioned by ESI. The need for complete barophenotypic characterization has been highlighted in the ESI recommendations. This includes the need for multiple anthropometric measurements, and addresses the syndromes of normal weight obesity, as well as sarcopenic obesity. The disparate diagnostic criteria for clinical obesity listed in the Lancet publication have been grouped in a reader friendly 4M format (medical, musculoskeletal, mood related and monetary) in our recommendations. The ESI statement lays equal emphasis on the psychosocial as well as biomedical determinants and downstream effects of obesity. Thus, they offer a balanced perspective of the syndrome. The threshold of diagnosis of clinical obesity, or the threshold of intervention, is not based on BMI alone. This message is evidence in the ESI document as well, which calls for a comprehensive evaluation of the patient. The various interventions available, and practical means of behavioural therapy, are detailed in the ESI recommendation, too. The ESI guidelines represent a person-centred approach to obesity management. This is evident in our continued use of the word ‘overweight’, which we feel is less stigmatizing, less threatening, and more person friendly than obesity. At the same time, the guidelines offer definitive advice regarding thresholds of intervention, whether by non-pharmacological, pharmacological, or surgical means. With regular updates and addenda, read in conjunction with global advances in obesity science, the ESI guidelines will continue to serve as the bellwether upon which Indian obesity care will function. SECTION B – NEXT GENERATION MEDICINES FOR OBESITY MANAGEMENT Liraglutide Glucagon-like peptide 1 (GLP1) receptor agonist liraglutide has 97 percent sequence homology to human GLP-1 [Table 1]. The half-life of liraglutide is 11 to 13 hour due to its avid binding to serum albumin.[31,32] LEADER trials are the phase 3 clinical trials of liraglutide on glycaemic efficiency of the drug in patients with type-2 diabetes mellitus. With the use of doses of 1.2 mg and 1.8 mg subcutaneous liraglutide daily, the Hba1c reduction have been 1.1%–1.8% and the weight loss documented have been 2–3 kg across the LEADER trials.[33] However, Liraglutide reduces body weight in a dose dependent manner. People with obesity without diabetes lost a mean weight of 6.2–8 kgs (7.4% body weight) with 3 mg of daily injectable liraglutide in Satiety and Clinical Adiposity—Liraglutide Evidence clinical trial (SCALE) trials.[34,35] Liraglutide 3 mg has also been investigated in patients with diabetes and obesity (SCALE Diabetes and SCALE insulin).[34,35] When liraglutide 3 mg was tried in people with diabetes and obesity with three oral antidiabetic medication the weight reduction observed was 6% with liraglutide vs 2% kg with placebo and when liraglutide 3 mg was used in population with obesity and diabetes on insulin the weight loss was 5.8% vs 1.2% in placebo arm.Table 1: Currently approved medications for obesity managementSemaglutide Semaglutide is currently one of the potent and efficacious GLP-1RA approved for weight loss and diabetes. Semaglutide is approved in once daily oral formulations (3, 7 and 14 mg) and once weekly (OW) SC (0.5, 1.0 and 2.0 mg) dosage for the management of type-2 diabetes mellitus and injectable semaglutide 2.4 mg OW for management of weight loss.[31-33] However, only the oral formulation is available in India for management of type-2 diabetes and Injectable semaglutide 2.4 mg has been approved by drug controller general of India for obesity management [Table 2]. However, injectable form is likely to be available in the next 24 months in a generic form.Table 2: Upcoming drugs for obesity managementInjectable semaglutide Semaglutide Treatment Effect in People with Obesity (STEP) trials are the phase 3 clinical trial program with semaglutide 2.4 mg OW for the management of obesity. Semaglutide 2.4 mg showed weight loss of up to 17.4% at the end of trial and one third of patients lost >20% of their baseline body weight.[36-43]Table 3 summarized different STEP trials. Participants who received semaglutide 2.4 mg over 104 weeks achieved a mean weight loss of 15.2% demonstrating a persistent effect of weight loss and other weight-related endpoints over a 2-year period. STEP 1 extension trial showed discontinuation of therapy for 1 year will lead to regain of two third of lost body weight. STEP trials also showed improvement in cardiometabolic risk factors like reduction in blood pressures, lipids and Hs C-Reactive Protein (CRP) levels.[37-43] More than 80% of subjects reversed to normoglycemia from prediabetes in STEP trials. Inj semaglutide has been approved for the management of obesity in children of 12 years of age and above based on STEP TEEN trial.[44] SELECT, a cardiovascular outcomes trial with semaglutide 2.4 mg has shown significant reduction (20%) in 3 point major adverse cardiovascular events in patients with overweight or obesity along with CVD.[45] Semaglutide also showed functional improvement in heart failure with preserved ejection fraction (HFpEF) in obese patients in STEP HFpEF trials. STEP trials have also showed the safety profile of semaglutide is in line with other GLP-1RAs as a class. Most common side effects are GI adverse events which are transient and mild to moderate in nature.[37-43]Table 3: STEP: Phase 3 clinical trial programme for Inj Semaglutide 2.4 mg[ 6-13 ]Oral semaglutide Oral semaglutide of 14 mg has been comparable to 1 mg injectable semaglutide in terms of weight reducing potential. PIONEER PLUS trial has taken higher strengths of oral semaglutide (25 mg and 50 mg) in people with obesity and type-2 diabetes mellitus.[46] In this trial oral semaglutide 50 mg showed a significantly higher weight loss vs. oral semaglutide 14 mg (−9.2 vs. −4.5 Kg, P < 0.0001) at the end of 68 weeks. However, OASIS 1 trial has taken 50 mg oral semaglutide against placebo in people living with obesity without T2DM showing a placebo-subtracted weight loss of −15.6% at week 68.[46] Cagri-Sema Cagri-Sema, a combination of Semaglutide and Cagrilintide is expected to further revolutionize the obesity management. Cagrilintide, is a novel long-acting amylin analogue peptide. In the hypothalamus and hindbrain, cagrilintide and semaglutide both target neurons that are relevant for homeostatic and hedonic food intake via different receptors.[47] Both will lead to weight loss via reduced appetite and cravings, improved control of eating and reduced calorie intake.[48] Cagrilintide has a half-life of 180 h thus can be used in combination with semaglutide as a once weekly injection for synergistic weight loss benefits. CagriSema has potential to provide additional weight loss without compromising tolerability. CagriSema appears to have a safe and well-tolerated profile in people with overweight and obesity.[49] In a phase 2 study Cagrilintide 4.5 mg OW alone showed weight loss up to 10.8% after 26 weeks. Weight loss increased with increasing dose of cagrilintide with significantly greater weight loss after 26 weeks at all dose levels vs. placebo, and for 4.5 mg vs. liraglutide 3.0 mg. GI adverse event and treatment discontinuation rate were lower with cagrilintide in comparison to liraglutide 3.0 mg.[49] In a phase 1 study by Enebo et al.,[50] compared semaglutide 2.4 mg alone to the same dose of semaglutide combined with increasing doses of cagrilintide [Table 4]. Remarkably, over a period of 20 weeks, the combination therapy achieved a weight loss of up to 17.1%. This level of weight reduction exceeds what has been previously observed with any other weight loss treatment, highlighting the potential effectiveness of this combined approach.Table 4: Phase 1 study of Cagri-SemaCurrently, Cagrisema is undergoing a robust phase 3 clinical trial program with the name of REDIFINE to evaluate efficacy and safety of Cagri-Sema in obesity. The recently announced topline results from REDIFINE 1 trial [Table 5] showed weight loss of 22.7% with cagrisema after 68 weeks compared to a reduction of 11.8% with cagrilintide 2.4 mg, 16.1% with semaglutide 2.4 mg and 2.3% with placebo in participants with overweight or obesity, while achieving a well-tolerated safety profile.[51]Table 5: REDIFINE Phase 3 program for Cagri-Sema[ 24-30 ]Tirzepatide Tirzepatide is an imbalanced dual agonist with glucose-dependent insulinotropic polypeptide (GIP) activity similar to the native molecule and GLP-1 activity five times lower.[52] It has a half-life of 5 days due to a C20-fatty acid chain attached to the 39 amino acid peptide chain.[53] It enhances insulin secretion: in the first and second phases and reduces the plasma glucagon levels resulting in glycaemic control.[54] It also causes weight loss by delaying gastric emptying and suppressing the appetite.[55] The initial clinical trials for Tirzepatide were done in people with type 2 diabetes and were named the SURPASS trials, which showed significant weight reduction in these participants. This led to the development of the SURMOUNT trials that was designed specifically to look at the obesity outcomes. SURMOUNT 1 was a Phase 3 trial which studied the efficacy and safety of tirzepatide in patients with obesity. At 72 weeks, the mean percentage change in body weight was −15.0% with 5 mg weekly dose, −19.5% with 10 mg dose, and −20.9% with 15 mg dose. SURMOUNT 2 was the next phase 3 trial that followed SUMOUNT 1 but was conducted in people with type 2 diabetes mellitus. Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg was –12·8% and with 15 mg was –14·7%.[56] SURMOUNT 3 was performed to study the effects of tirzepatide on weight reduction after 12 weeks of Successful (≥5% weight reduction) intensive lifestyle intervention. The results showed that the coprimary endpoint of additional mean per cent weight change from randomization to week 72`Q was met with changes of −18.4% (0.7) with tirzepatide and 2.5% (1.0) with placebo treatment percentage The coprimary endpoint of the percentage of participants achieving additional weight reduction was met with with tirzepatide and with placebo achieving this In SURMOUNT the continued Treatment with Tirzepatide for of Weight in with Participants who the period a mean weight reduction of The mean percent weight change from week to week was with tirzepatide vs with It is available in the Indian and is approved for weight loss in India. It as a of mg and 5 mg and is to be in the between and is at a lower dose of mg per week which is increased to 5 mg after weeks. It is further increased with mg per to a dose not 15 mg. subcutaneous the to plasma of tirzepatide from to 72 The mean of tirzepatide following subcutaneous was plasma tirzepatide were achieved following weeks of dose is required for or data on end and is The is in the or once a without any to the It be given as or The of be In of a dose, the is less than the dose as as with the next dose at its the is more than the dose and the next dose at the The of weekly can be as as is more than between the two be in patients with BMI kg/m2 or in individuals with a BMI kg/m2 with at one associated as type 2 diabetes and Tirzepatide be where a weight loss target of is Both tirzepatide and injectable semaglutide be where a weight loss target of only is SECTION – FOR is an of anti-obesity medication is required not only to but therapy as The and of medication to the type and dose of drug However, the of the use the format to a for anti-obesity medication This can be used by and to the person living with obesity, and their to the use of This will from person to and to The and of the with the care the need for as the of due to obesity. The potential and of of be shared in a manner. The of weight as well as cardiovascular and can be using relevant and medications are one of the management for obesity. use not the need for and regular at and complications of obesity are also along with A is also while or therapy for obesity. The expected of weight can be from the results of trials. This can be shared with individuals obesity treatment. The of be While the need for weight therapy is a for therapy to the efficacy and of a can be effects The of adverse be mentioned that these are mild and and to [Table in reducing the due to these A evaluation to out as and disease, can the risk of adverse be that these effects are a that the drug has of adverse is an of health care and in This be at the A of obesity medication the of obesity, and its in The use of anti-obesity medication reduction of other or blood therapy, thus to cost or with lower or less be to It be that these are not by any medication to be and is therapy for obesity be with the to their and They also be the of medication for of subcutaneous and of and of be is in women of who to anti-obesity medication or This continue for 3 months after of and months after on oral to a as containing or a when tirzepatide is or be required in some on as or and those with higher for approach and be obesity of the obesity care be in and is obesity care that this to their be based on and shared medication and treatment, that the person with obesity and Thus, obesity can be in a and manner. in and of outcomes. for anti-obesity medications their The continue the treatment. adverse and cost of the anti-obesity medications be a of the 3 be about the of anti-obesity for in women of age is SECTION MANAGEMENT OF OBESITY Obesity is not as a but as a that The rising prevalence of obesity that is by various and lead to to food and the obesity among the be can an in to lifestyle can be using validated designed specifically for family related to health The Health is one that of regarding activity and health related to obesity for adults need to be The of family in clinical can be family in clinical can the for individuals undergoing obesity treatment. that is for weight outcomes in children and interventions can lead to to changes and activity recommendations. family treatment can that to obesity. that are by family the family in treatment outcomes than on the intensive behavioural therapy that family have shown in lifestyle changes by at where individuals and in their weight management can a of of other individuals lifestyle change can some that can eating or and be in health can that lifestyle in or where individuals can in or can among participants. can among who for like or to In this as can be to while like can of while can be in by lifestyle of the obese be while management of obesity. be while management of obesity. and family be in clinical that they can be regarding and activity and serve as a for individuals undergoing obesity treatment. available, be where individuals can with other living with obesity. in or led be The is an update to the previously published clinical practice guidelines published by the endocrine society of India. This be read and in clinical practice with the previous and not to provide a comprehensive management for management of obesity in people living India. This the recent newer medications and the advice that be given when these these guidelines provide the most on obesity is to that same management for all people living with obesity. The treatment be and based on of person to the and of are of of was not used in or of the

In India, the increasing prevalence of diabetes and obesity poses a significant threat towards a surge in the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). Concomitant with the evolving guidelines, there is a need to direct and spread awareness among practicing diabetologists to identify and screen high-risk individuals for MASLD for timely management. Its asymptomatic nature and the evolving guidelines on diagnosis have hindered the precise estimates of MASLD in the high-risk group of individuals in a clinical setting. Therefore, an expert panel of diabetologists from India convened to review, discuss and document the approach towards screening, diagnosis and management of MASLD. Serum biomarkers, simple non-invasive tools and imaging techniques could direct the risk stratification of the patients. Early lifestyle interventions including weight loss and exercise are beneficial. The pharmacological landscape of drugs directed to insulin resistance, lipid metabolism, oxidative stress, inflammation, apoptosis and fibrogenesis pathways for the management of MASLD is expanding. In summary, the consensus statements are expected to serve as a useful guide in the screening and management of MASLD in the region and to direct a well-planned study design that could enhance the scientific value of these statements.

Sarcopenia, an age-related condition marked by the decline of skeletal muscle mass, strength, and function, often leads to loss of function, disability, and diminished quality of life (QoL) in the elderly population. Despite its growing prevalence, sarcopenia is frequently underdiagnosed and inadequately managed. Timely detection and appropriate interventions are crucial to slowing disease progression and minimizing associated risks. As standardized guidelines and individualized management plans are necessary to improve clinical outcomes, this consensus paper presents expert insights into advancements in sarcopenia management, including diagnostic criteria and therapeutic interventions, and the need for personalized screening tools for Indian demographics. Furthermore, experts emphasized the importance of a multimodal approach, integrating resistance exercise, nutritional optimization, and emerging pharmacological therapies for effective sarcopenia treatment. The role of anabolic agents such as nandrolone decanoate in muscle preservation is explored, alongside considerations for patient selection and safety. This paper underscores the importance of a patient-centered approach, which addresses both functional recovery and overall well-being of individuals at risk or diagnosed with sarcopenia.

Idiopathic hypercalciuria (IH) is a metabolic condition characterized by excessive calcium excretion in urine without identifiable secondary causes, such as hyperparathyroidism or malignancy. It is a significant clinical entity due to its association with kidney stones, nephrocalcinosis, and osteoporosis, leading to reduced quality of life and long-term complications. This comprehensive review discusses the pathophysiology, clinical manifestations, diagnostic strategies, and management approaches for IH. The disorder arises from a multifaceted interplay of renal, intestinal, and skeletal factors. Impaired renal tubular calcium reabsorption, heightened intestinal calcium absorption, and increased bone resorption are key contributors to its pathogenesis. Genetic predispositions, including mutations in calcium-regulating receptors and transporters, further complicate its etiology. Patients often present with kidney stones, bone pain, or reduced bone mineral density, although asymptomatic cases are not uncommon. Diagnosing IH requires a thorough evaluation to exclude secondary causes, with 24-hour urinary calcium excretion serving as a crucial diagnostic marker. Management focuses on mitigating complications and improving quality of life through hydration, dietary modifications, and pharmacological therapy. Thiazide diuretics are the cornerstone of treatment, effectively reducing urinary calcium levels and preventing stone formation. Adjunctive measures include citrate supplementation and lifestyle interventions such as weight management and adequate physical activity. For patients with severe nephrolithiasis or nephrocalcinosis, surgical intervention may be necessary. Despite significant advancements, IH remains a diagnostic and therapeutic challenge due to its diverse clinical presentations and underlying mechanisms. A multidisciplinary approach, incorporating tailored medical and dietary strategies, is essential for optimal management. Future research into its genetic and molecular basis holds promise for developing more targeted interventions and improving patient outcomes. This review aims to provide a practical, up-to-date guide for clinicians managing this complex yet common metabolic disorder.

The burden of type 2 diabetes mellitus (T2DM) is increasing in India, with increasing mortality and morbidity. In India, T2DM management is complicated by the presence of distinct clinical characteristics as well as certain socioeconomic factors of the patient population. These factors affect glycemic control and lead to poorer outcomes, necessitating the use of add-on treatments with safer medications, which can be used over the long term with minimal follow-up. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that inhibits the activity of DPP-4, a peptidase that degrades glucagon-like peptide 1 (GLP-1), a glucoregulatory hormone. Sitagliptin enhances glucoregulation in people with T2DM as monotherapy, as well as in combination with other antihyperglycemic drugs, and has a low risk of adverse side effects. This review focuses on assessing the efficacy and safety of sitagliptin as an add-on therapy to other antidiabetic agents and insulin.

With the increasing intake of dietary fructose, primarily from sucrose and sweetened beverages, metabolic illnesses such as type 2 diabetes mellitus, hypertension, fatty liver disease, dyslipidemia, and hyperuricemia have become more prevalent worldwide, and there is also growing concern about the development of malignancies. These negative health impacts have been validated in various meta-analyses and randomized controlled trials. In contrast, the naturally occurring fructose found in fruits and vegetables contains only a minimal amount of fructose and, when consumed in moderation, may be a healthier choice. This review focuses on the biology of fructose, including its dietary sources, the physiology of its metabolism, and the pathological basis of various disorders related to high dietary fructose intake.

1. Which therapeutic strategy is currently being explored to disrupt the cancer stem cell CSC niche and inhibit tumor progression? Targeting the immune cells within the niche Inhibiting extracellular matrix (ECM) remodeling enzymes, such as matrix metalloproteinases (MMPs) Blocking glucose uptake to starve CSCs Increasing vascular endothelial growth factor (VEGF) expression to induce vascular normalization. Answer: (b) Inhibiting ECM remodeling enzymes, such as MMPs. Explanation CSC niche creates a bottleneck in the treatment of cancer as these are a subset of cells in minority which cause relentless growth of the cell. Moreover, these niches can evade chemo- and radiotherapy causing resistance to cancer therapy and have high tendency for metastasis. The microenvironment is made of cancer cells, fibroblasts, stromal and endothelial matrix (EM), blood vessels, signaling molecules, intrinsic factors, exosomes, and some other acellular components.[1] MMPs are enzymes involved in the breakdown of the ECM, a critical component of the CSC niche. MMPs, particularly MMP-2 and MMP-9, remodel the ECM, facilitating cancer progression by: (1) Promoting metastasis: by degrading ECM barriers, MMPs help CSCs invade new tissues. (2) Creating a permissive niche: the ECM remodeling allows the release of growth factors stored in the matrix and promotes angiogenesis, creating a supportive environment for CSCs. Therapeutically, targeting MMPs to disrupt ECM remodeling can: (1) Prevent the dissemination of CSCs by inhibiting their ability to migrate and invade surrounding tissues. (2) Alter the microenvironment to make it less supportive of CSC maintenance and survival, potentially making CSCs more vulnerable to treatment. Several MMP inhibitors[2] have been developed, though challenges remain in ensuring their specificity and reducing side effects. 2. Which of the following describes a potential advantage of using liquid biopsy to detect epigenetic changes in cancer? It allows for the identification of mutations in coding regions only It focuses on detecting histone modifications in tumor samples It can be used to permanently alter the patient’s epigenome It provides a noninvasive method to monitor DNA methylation patterns in real-time. Answer: (d) It provides a noninvasive method to monitor DNA methylation patterns in real-time. Explanation Liquid biopsy is an advanced, noninvasive diagnostic technique that analyzes biomarkers such as circulating tumor DNA (ctDNA), which can be found in bodily fluids like blood. This technique is valuable in cancer management because it enables real-time monitoring of tumor dynamics without needing invasive tissue biopsies. Although it cannot replace solid tumor biopsies, it can give insight to DNA methylation as a marker of epigenetic changes and can be easily repeated.[3] 3. Which of the following is the first food and drug administration (FDA)-approved drug (targeted therapy) for pediatric patients <12 years of age with rearranged during transfection RET alterations? Pralsetinib Selpercatinib Lenvatinib Vandetanib. Answer: (b) Selpercatinib. Explanation The RET gene encodes a receptor tyrosine kinase protein that plays an essential role in several biological processes, especially in the development of the nervous system, kidneys, and certain types of tissues. The RET protein helps regulate cell growth, differentiation, migration, and survival. It also functions as a co-receptor in a signaling complex with members of the glial cell line-derived neurotrophic factor (GDNF) family ligands. These ligands bind to a co-receptor called GFRα (GDNF family receptor α), which then binds and activates RET, leading to intracellular signal transduction. Selpercatinib is a RET inhibitor and is used as targeted therapy to treat cancers associated with abnormalities in the RET gene – RET mutations or fusions. Such RET can act as an oncogene in various cancers. The RET fusions retain the kinase domain and behave as drivers of nonsmall cell lung cancers (NSCLC) and papillary thyroid cancer, and activating RET mutations lead to different phenotypes of multiple endocrine neoplasia type 2 and sporadic medullary thyroid cancer (MTC).[4] 4. A 49-year-old female presented with progressive dyspnea and worsening cough. On further investigation, a mass was found in the perihilar region of the right lung with features of nonsmall cell bronchogenic carcinoma, and molecular analysis showed p53 gene mutation. The most likely mechanism of neoplastic transformation is? Transcriptional activation Loss of cell cycle arrest Inhibition of apoptosis Microsatellite instability Answer: (b). Explanation p53 gene is a tumor suppressor gene responsible for causing cell cycle arrest in the late G1 phase when there is DNA damage, thus allowing DNA repair. p53 mutation involving both the alleles leads to many human cancers like mutations occurring in around 50% of cases and small cell lung cancer in 75%–90% of cases.[5] Transcriptional activation is a feature of MYC proto-oncogene. Inhibition of apoptosis is caused by B cell Lymphoma 2 (BCL2) mutation. Microsatellite instability is a feature of genes that repair DNA damage. 5. The key regulatory protein involved in controlling metabolic reprogramming and switch from oxidative phosphorylation to glycolysis in tumor cells is? HIF-1α mTOR p53 AMPK Answer: (a). Explanation Hypoxia-inducible factor (HIF-1) α is the primary regulator of the “metabolic reprogramming” of the cancer cells. HIF-1 induces glycolysis by upregulating the expression of GLUT and multiple key enzymes of glycolysis and TCA cycle in conjunction with many proteins. Increased expression of HIF-1α is associated with poor prognosis.[6] The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase in the PI3K-related kinase family and has a significant role in cell proliferation and metabolism. mTORC1 is involved in cellular metabolism (protein synthesis, lipid synthesis, and mitochondrial activity), whereas mTOR2 specifically participates in glutamine metabolism. p53 is a tumor suppressor gene; mutation in p53 results in increased activity of glycolytic flux, pentose phosphate pathway, lipid metabolism, and decreased mitochondrial respiratory activity. Adenosine monophosphate-activated protein kinase (AMPK) plays an important role in glucose uptake by increasing the expression of GLUT and promoting glycolysis regulating phosphofructokinase (PFK) and various other enzymes. 6. What is the role of increased lactic acid production in the tumor cells? Activates c-myc which in turn increases expression of glutamine transporter protein Increases angiogenesis and promotes metastasis Modulation of immune cell activity All of the above Answer: (d). Explanation Lactate from tumor and stromal cells acidify the tumor microenvironment and promote tumor cell proliferation and metastasis by altering the metabolic pattern of multiple cells including immune cells. Lactate is thus involved in the promotion of survival of the tumor cells, oncogene signaling, spread/metastasis, and immunosuppression. Lactate also stabilizes HIF-2 α, which stabilizes c-Myc protein expression in the nucleus. c-Myc in turn promotes glutamine transporter protein 2 (GLUT2) expression and glutaminase 1 (GLS1) which catalyzes the breakdown of glutamine to glutamate in the mitochondria. In the mitochondrial matrix, glutamate is converted to α-KG (ketoglutarate) and enters the tricarboxylic acid cycle.[7] 7. A 45-year-old male presents to the dermatology clinic with complaints of an itchy rash on his back, arms, and legs that developed over the last few days. He describes the rash as streak-like and reports that it appeared suddenly after experiencing mild itching. He also reported feeling fatigued and has been experiencing intermittent fevers. On examination, it was observed linear, erythematous streaks across his back and upper arms resembling whip marks. The patient has a history of testicular cancer and is undergoing chemotherapy as part of his treatment plan. His regimen includes bleomycin, dactinomycin, and etoposide. The remainder of his examination is unremarkable. Based on the patient’s clinical history and examination, which drug is responsible for skin pigmentation? Bleomycin Etoposide Vinblastine Dactinomycin. Answer: (a). Explanation Bleomycin is a chemotherapeutic agent that cause distinctive type of skin pigmentation called flagellate pigmentation. It is characterized by linear streaks of hyperpigmentation that resemble the tracks left by whip of the flagellum.[8] 8. A 40-year-old woman named Lata has been diagnosed with Stage III breast cancer and has been recommended for chemotherapy. She has a history of myocardial infraction. Which antineoplastic drug should be avoided in her treatment? Alkylating agents Platinum compounds Anthracyclines Paclitaxel. Answer: (c) Anthracyclines. Explanation Chemotherapy drugs for advanced breast cancer are taxanes, anthracyclines, platinum agents, and trastuzumab. Two forms of cardiotoxicity are observed with anthracyclines. The acute form occurs within the first 2–3 days and presents as arrhythmias and conduction abnormalities, other electrocardiographic changes, pericarditis, and myocarditis. The chronic cardiac toxicity appears to result from increased production of oxygen-free radicals within the myocardium.[9] Recently approved dexrazoxane helps in reducing the cardiotoxicity induced by anthracyclines. It acts an iron chelator and removes the free iron as well as the iron bound to doxorubicin. Since this reduces the free radical generation in this manner, it is said to be cardioprotective.[10] 9. A patient diagnosed with head-and-neck cancer was given radiotherapy. After 45 days of radiotherapy, chemotherapy was started but the patient presented with discolored and inflamed skin limited to the region that had previously been irradiated, the clinical picture as shown after the start of chemotherapy. What is the likely drug responsible for this? Doxorubicin Carboplatin Methotrexate Cetuximab. Answer: (a) Doxorubicin. Explanation The clinical picture shows “radiation recall” syndrome. The causative agent is doxorubicin. It is related to an interaction between chemotherapy and radiation therapy. Radiation causes damage to DNA of cells in targeted areas and this damage persists for some time. Chemotherapy interacts with residual radiation damage, triggering inflammatory response in previously irritated tissue. Methotrexate causes mucositis and skin reaction but is not associated with radiation recall. Cetuximab, a monoclonal antibody, causes other skin reactions. 10. HER-2 overexpression in breast cancer is associated with: More aggressive and lethal form of cancer Low metastasis rate and good prognosis Better prognosis due to positive response to hormone therapy None of the above. Answer: (a). Explanation Human epidermal growth factor receptor 2 (HER2) is a gene encoding growth factor receptor, which activates intracellular signaling pathways. HER 2 overexpression and mutation are found in breast, colorectal, bladder, gastric, esophageal, endometrial, and ovarian cancers. HER2 overexpression implies more aggressive and lethal form of cancer. Therapies targeting HER2 (trastuzumab) have shown increased survival and prevention of cancer progression.[11] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Abstract Vitamin D-dependent rickets type 1A is caused by pathogenic variants of CYP27B1 gene, which is inherited in autosomal recessive pattern. These variants lead to defective 1α-hydroxylase enzymatic activity, leading to impaired renal formation of 1,25(OH)2 vitamin D. We report a case of a 16-year-old Asian male patient, with short stature and progressive bone deformity, whose biochemical parameters revealed low levels of 1,25(OH)2 vitamin D, low serum calcium levels, along with high phosphorus and raised levels of intact parathyroid hormone. These biochemical parameters suggested the diagnosis of pseudohypoparathyroidism. The patient also had concurrent extrapulmonary tuberculosis during the time of presentation to our endocrine unit. However, on molecular testing, it was revealed that the patient was harboring pathogenic variants of the CYP27B1 gene, in a compound heterozygous manner, with a novel missense mutation in exon 6 of the CYP27B1 gene, c.1136G &amp;gt; C (p.Arg379Thr), suggesting the diagnosis of vitamin D-dependent rickets type 1A. The cause of high phosphorus at the time of presentation, which led to a diagnostic dilemma of pseudohypoparathyroidism, was later explained by presence of active extra pulmonary tuberculosis. This report describes a case of vitamin D-dependent rickets type 1A, mimicking pseudohypoparathyroidism owing to presence of concurrent illness like extrapulmonary tuberculosis.

Colours of India is an annual cultural phenomenon that transcends the boundaries of professional conferences, uniting endocrinologists through the universal language of music and dance. Since its inception in 2016, this vibrant event has brought together teams from across India and other participating countries, showcasing diverse dance forms while fostering friendships, promoting wellness, and celebrating cultural diversity within the medical community.

India has a high prevalence of type 2 diabetes mellitus (T2DM) with unique clinical characteristics compared to other populations. Despite advancements in diabetes therapy, a significant number of patients in India still experience poor glycemic control and complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors continue to be an important component of T2DM treatment due to their favorable efficacy and tolerability profile. Given the current scenario, there is a need to revisit the role of DPP-4 inhibitors in T2DM management in Indian patients. This consensus paper aims to provide guidance on the utilization of DPP-4 inhibitors in T2DM management from an Indian perspective. A consensus group of 100 experts developed recommendations based on an extensive literature review and discussions. The expert group emphasized the importance of timely glycemic control, combination therapy, and targeting the underlying pathophysiology of T2DM. The combinations of DPP-4 inhibitors with metformin and/or sodium-glucose transport protein-2 inhibitors are rationalized in this paper, considering their complementary mechanisms of action. This paper provides valuable insights for clinicians in optimizing the management of T2DM in the Indian population with the use of DPP-4 inhibitors and proposes an algorithm for selecting DPP-4 inhibitor-based therapies.

Exercise is one of the pillars of diabetes management. Current guidelines provide a general recommendation regarding exercise advice for patients with diabetes, but guidance regarding exercise suited for Indian patients is scarce. We aim to arrive at exercise recommendations for patients with type 2 diabetes incorporating the latest modalities of exercise along with consideration of Indian patients. We conducted an extensive search using the PubMed electronic database and Google Scholar until February 1, 2024. The retrieved literature was then meticulously deliberated upon by the panel members to arrive at appropriate recommendations. The various guidelines and literature recovered have advised exercise regimes for type 2 diabetes, but have not always covered all the aspects of exercise, including timing of exercise, exercising in the presence of associated comorbidities such as diabetic foot, neuropathy, retinopathy, cardiovascular disease, elderly, and pregnancy with diabetes in one complete recommendation. Furthermore, advice regarding soleus exercise has not been incorporated in any recommendation. Moreover, advice specifically for Indian patients with type 2 diabetes was lacking. This recommendation incorporates the latest in exercise modalities for patients with type 2 diabetes, including patients with major macrovascular and microvascular problems, with specific advice for each complication which will serve as a guide for physicians when they advise patients regarding exercise.

Hypoglycemia is common in diabetic populations using insulin or insulin secretagogues, but rare in non-diabetics. A 60-year-old non-diabetic male presented with repeated episodes of abnormal behavior persisting for 10-15 minutes for seven days, associated with sweating, intense hunger, and relief on food intake, with no history of insulin or secretagogue intake, with stable vitals and normal systemic examination. Laboratory tests during attacks revealed low blood sugar, high serum insulin, and normal C-peptide levels, with no evidence of pancreatic or extrapancreatic hyperinsulinism, and serum anti-insulin antibody levels >100 U/ml. Based on these results, he was diagnosed with autoimmune insulin syndrome (AIS). Treatment with low-carb meals, oral prednisolone, and acarbose led to the resolution of symptoms. Hirata syndrome, though rare in India, requires consideration as a differential diagnosis to avoid unnecessary invasive procedures.

Abstract Hyperglycemia is considered one of the main risk factors for the development of cardiovascular diseases, and the situation becomes worse if the condition is associated with uncontrolled hypertension, dyslipidemia, and overweight or obesity. Since the first glucagon-like peptide 1 receptor agonist (GLP-1RA) being approved in 2005 for type 2 diabetes, the class has successfully developed newer compounds with more pronounced effects on glycemic control and body weight; not to forget the oral peptide in a pill as well; oral semaglutide. To manage hypertension, obesity, lipids, and diabetes, it is ascertained that a holistic approach is required or the class with pleiotropic benefits to treat accompanying metabolic disturbances. Over the years, the place for GLP-1RA therapy has changed with most guidelines recommending GLP-1RA therapy in patients with established or high risk of cardiovascular disease independently of glycemia.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (β-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and β-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Objectives: The aim of the STAR survey was to understand the physicians’ knowledge, attitude and perception regarding the role of nutritional dietary fiber supplements in the daily management of type 2 diabetes mellitus (T2DM). It also aimed to compare the changes in glycemic parameters as well as energy and satiety levels between patients taking a high-fiber supplement and those not taking a fiber supplement. Methods: Two cross-sectional pan-India surveys were conducted. The first was among 152 physicians who had &gt;5 years of experience in treating patients with T2DM and treated &gt;50 patients with T2DM per month. A self-administered paper-based questionnaire was used for the survey. The other survey was conducted among 3,042 patients with T2DM who were receiving treatment with antidiabetics. These patients were further categorized into the Horlicks Diabetes Plus (HDP) group, which consisted of 1,524 patients who had consumed the HDP fiber supplement for a minimum of 3 months and the non-HDP group, which included 1,518 patients who had never consumed HDP. Results: Almost all physicians prescribed fiber-rich nutritional supplements to their patients with T2DM and believed that dietary fiber has an important role in managing glycated hemoglobin (HbA1c) values, healthy weight and cholesterol levels. Among the main benefits of HDP seen by physicians were improvement in satiety levels and increase in physical activity, reduction in HbA1c, fasting and postprandial glucose, and reduction in dose and/or number of hypoglycemic medications. All physicians recommended that it was important to increase awareness among patients as well as doctors regarding the benefits of HDP in patients with T2DM. Patients in the HDP group reported a mean decrease of 0.72 in their HbA1c value which was statistically significant at 3 months (8.04 at baseline to 7.32 at 3 months). In contrast, the non-HDP group showed a non-statistically significant decrease of 0.61 in HbA1c from a baseline value of 8.15. Furthermore, patients reported a significant decrease in weight of 3 kg in 3 months from baseline value of 72.11 kg to 69.11 kg. This reduction in weight was observed in 82% patients in the HDP group, while the non-HDP group showed an insignificant weight reduction from a baseline value of 72.14 kg to 71.46 kg in 3 months. About 83% of patients reported feeling full for longer periods of time and 92.62% reported feeling more energetic after starting HDP. The compliance and satisfaction rates with HDP were 96% and 75%, respectively. Conclusion: A high-fiber supplement taken along with patients’ existing antidiabetic treatment plan has the potential to decrease glycemic parameters and weight while increase the satiety and energy levels among patients with T2DM. However, these results need to be evaluated further with long-term clinical studies conducted in the real world.

Vitamin D Deficiency Eradication: A National Priority

Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential concept to assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.

Inadequate glycaemic control post-discharge is the root cause of readmission in people with diabetes mellitus (DM) and is often linked to improper discharge planning (DP). A structured DP plays a crucial role in ensuring continuing home care and avoiding readmissions. DP should help patients in self-care and provide appropriate guidance to maintain optimal glycaemic control. There is a scarcity of reports and recommendations on the proper DP for people with DM on insulin therapy. The present review provides important consideration based on experts' opinions from the National Insulin and Incretin summit (NIIS), focusing on the effective treatment strategies at the time of discharge, especially for insulin therapy. A review of literature from PubMed and Embase was conducted. The consensus was derived, and recommendations were made on effective DP for patients with DM. Recommendations were drawn at the NIIS for post-discharge treatment for medical and surgical cases, stress-induced hyperglycaemia, elderly, pregnant women, and coronavirus disease 2019 (COVID-19) cases. The committee also recommended a comprehensive checklist to assist the physicians during discharge.

Organophosphorus Compound Poisoning is one of the most common toxicological emergencies encountered particularly in rural agricultural patients presenting to the emergency department of Hitech Medical College and Hospital in Bhubaneswar, Odisha. Atotal 372 cases of organophosphorus compound poisoning were analyzed during the three-year period from January 2017 to December 2020. The basic demographic data such as age, sex, socioeconomic status, occupation along with specific data such as motive of poisoning, types of compound consumed with its quantity, distance from referral place and the final prognosis. The commonest patients were Young Male agricultural workers. Suicidal intent mainly due to financial crisis was seen to be the commonest among both males and females with Dichlorovos being the most used poison. Of all the cases there were three cases of respiratory failure resulting in multi organ failure.

Hypothyroidism is a common endocrine disorder affecting 1%–10% of the population. To date, levothyroxine (LT4) monotherapy is the standard of care in the management of hypothyroidism. However, approximately, 5%–10% of patients who normalize thyroid-stimulating hormone levels with LT4 monotherapy may have persistent symptoms that clinicians may attribute to tissue hypothyroidism. A long-standing debate in the literature iswhether the addition of levotriiodothyronine (LT3) to LT4 will ameliorate lingering symptoms. However, patients with hypothyroidism who have persistent symptoms despite the exclusion of other comorbid conditions or nutritional deficiencies and patients with specific genetic mutations in deiodinase enzyme may respond to a trial of LT3 alone or in combination with LT4 therapy. This article intends to review the current literature available to understand the drawbacks of thyroxine (T4) monotherapy, establish the concept of T3 + T4 combination therapy, its safety and efficacy based on evidence, recommendations from guidelines, and its implications.