Prevalence and Association of Risk Factors According to Liver Steatosis and Fibrosis Stages among Nonalcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus in India: A Cross-sectional Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are linked to the global diabetes epidemic, leading to increased disease progression and adverse health outcomes. The renaming of NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD) at the 2023 European Association for the Study of the Liver Congress highlights the complex relationship between metabolic disorders and liver health. Taking this into consideration, we aimed this study to identify prevalence and risk factors associated with the stages of NAFLD in individuals with T2DM in the Indian population. MATERIALS AND METHODS: This observational, cross-sectional study was conducted on 1,521 T2DM patients at Dr Panikar's Speciality Care Centre, Mumbai, between September 1, 2022 and October 31, 2022. Demographic parameters such as age, gender, height, weight, and anthropometric parameters such as body mass index (BMI) and waist circumference were measured. Liver fibrosis and steatosis stages were identified by vibration-controlled transient elastography (VCTE) using FibroScan®. RESULTS: The prevalence of liver steatosis was 75.1% among the 1,521 diabetes cases [S0 (24.9%), S1 (15.1%), S2 (24%), and S3 (36%)], whereas the prevalence of liver fibrosis was 28.0% [F0 (72%), F1 (19%), F2 (5%), F3 (1.5%), and F4 (3.4%)]. The S1 (p = 0.012), S3 (p = 0.001), F1 (p = 0.001), and F2 (p = 0.001) grades showed significant gender-related changes, demonstrating a positive connection. Furthermore, waist circumference was associated with disease severity in both liver steatosis and fibrosis stages (p = 0.001), but BMI was solely associated with the degree of steatosis (p = 0.001). The mean age differences between these categories, however, did not reach statistical significance (p-values of 0.149 and 0.078, respectively, for the steatosis and fibrosis grades). CONCLUSION: The study reveals a high prevalence of NAFLD (steatosis and fibrosis) in T2DM patients, increasing the risk of advanced fibrosis. In T2DM patients with risk factors including waist circumference and BMI, appropriate screening and intervention are required.

Edema India: Executive Summary of Screening, Diagnosis, and Management of Edema.

The management of edema requires a systematic approach to screening, diagnosis, and treatment, with an essential initial assessment to differentiate between generalized and localized edema. The Association of Physicians of India (API) aimed to develop the first Indian Edema Consensus (Edema India), offering tailored recommendations for screening, diagnosing, and managing edema based on the insights from the expert panel. The panel suggested when evaluating edema symptoms, important factors to consider include the patient's current illness, medical history, risk factors, family history, and medications. Key diagnostic investigations for edema include complete blood count, cardiovascular imaging and markers, deep vein thrombosis (DVT) assessment, along with renal, hepatic, and thyroid function tests. Edema management involves a combination of pharmacologic and nonpharmacologic interventions, including limb elevation, physiotherapy, compression therapy, fluid removal, diuretics (loop diuretics: first-line therapy), and a sodium-restricted diet. The panel believed that educating patients could foster a preventive mindset, helping to prevent the worsening of edema.

Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.

BACKGROUND: The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α1 receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin. MATERIALS AND METHODS: A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values. RESULTS: Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP. CONCLUSION: Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.

Fortifying Micronutrient Supplementation in India: Indian Expert consensus.

Micronutrients play a key role in human health, being involved in energy metabolism, immunity, cellular functioning, growth, and development. Deficiencies in micronutrients occur in individuals of all ages due to several factors, including inadequate diets, disease states, and overweight/obesity. Guidelines from the Indian Council of Medical Research (ICMR) National Institute of Nutrition (NIN) Expert Group on Nutrient Requirements for Indians (2023) have specified the Recommended Dietary Allowances (RDA) for macronutrients and micronutrients. In addition, a healthy diet is crucial for overall health and should be the first step toward addressing micronutrient deficiencies. When diet is inadequate, micronutrient supplements can be provided to compensate. An expert panel of Indian doctors was convened to develop a pathway toward micronutrient supplementation among the Indian population. This Consensus Statement recognizes that different populations have varying needs for specific micronutrients, and ensuring adequate intake of such micronutrients can improve health outcomes. The panel provided recommendations for dietary practices and micronutrient supplementation when diet is inadequate. Addressing micronutrient deficiencies at the primary care level can prevent chronic deficiencies and their consequences. This Consensus Statement can serve as a primer for physicians to monitor and address deficiencies and thus help individuals maintain their health.

Evolution of Metabolic Syndrome in Newly Diagnosed Type 2 Diabetes Mellitus Asian-Indian Patients Over the Last 15 Years using Adult Treatment Panel III of the National Cholesterol Education Program, World Health Organization, and International Diabetes Federation Criterion.

AIM: A retrospective observational study was undertaken to assess the changing trends in the incidence of metabolic syndrome (MetS) in Asian-Indian patients with newly diagnosed type 2 diabetes (T2D) using Adult Treatment Panel III of the National Cholesterol Education Program (NCEP-ATP III), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria. The overall and gender-wise pattern of MetS and its components were also evaluated. MATERIALS AND METHODS: Newly diagnosed T2D patients (n = 10,950)visiting Dr Panikar's Diabetes Care Centre from 2004 to 2019 with retrievable electronic medical records were selected. The incidence of MetS in these patients was studied using NCEP-ATP III, WHO, and IDF criteria in three separate timelines, namely, group I (2004-2008), group II (2009-2013), and group III (2014-2019). Overall and gender-wise, the incidence of various components of the MetS was also studied and compared across the three groups. All data were analyzed by using the Statistical Software Statistical Package for the Social Sciences (SPSS) version 10.0. Continuous variables were summarized by the number of observations (mean, standard deviation or median with minimum and maximum) and categorical values (calculating frequencies with percentages). Chi-square was used to estimate the incidence of MetS using different criteria and gender-wise patterns of the MetS components for the three periods. Other variables, such as mean body mass index (BMI), were assessed by applying variance analysis (ANOVA test). All values were reported based on a two-sided ANOVA test, and all the statistical tests were interpreted at a 5% level of significance. RESULTS: In the current study, the overall incidence of MetS observed among the study population was 80.9, 65.4, and 69.8% using NCEP-ATP III, WHO, and IDF criteria, respectively. The incidence of MetS across the three timelines (i.e., from 2004 to 2019) with all the diagnostic criteria showed a steady increase. An analysis of the individual components of MetS revealed a high incidence of central obesity across all subgroups, followed by hypertension and dyslipidemia. Central obesity was prevalent in nearly 85.9% of patients in 2014-2019 vs 78.6% in the 2004-2008 subgroup. Similarly, the incidence of hypertension and overall dyslipidemia [i.e., high triglycerides (TGs) and low high-density lipoprotein-cholesterol (HDL-C)] was 77.8% and 68.2% in the former vs 67.9% and 59.6% in the latter, respectively. The incidence of all three MetS components, along with fasting sugar, showed a statistically significant and progressive increase over the years, with prevalence in group III (2014-2019) being the highest. Women were found to be more centrally obese and more dyslipidemic compared to men, whereas men were found to be more hypertensive. CONCLUSION: The study shows a high incidence of MetS in Asian-Indian patients with newly diagnosed T2D. The incidence of MetS was significantly higher with the NCEP-ATP III diagnostic criteria than with WHO and IDF criteria. A steady rise in the incidence of MetS was observed over the study period of 2004-2019. Among the components of MetS, the incidence of central obesity, elevated TG levels, and low HDL-C were found to be higher in the female population than in males, whereas the incidence of hypertension was higher in males. Stringent lifestyle measures, along with appropriate pharmacological management, might help mitigate the risks associated with MetS.

Going Green: Climate Change and Health.

The World population doubled from 4 billion humans to 8 billion humans from 1974 to 2022, and it is unlikely to double again. The population of India has now surpassed China, with around 1.4 billion, and we have also already climbed up to become the world's fifth largest economy. Unfortunately, rapid economic development, urbanization, and modernization bring with them deleterious effects on national health, especially if the population does not take preventive measures to protect themselves. Additionally, economic development incorporates rapid industrial and agricultural advances, all of which impact the environment directly.

Randomized, Double-blind, Phase III Trial of Lobeglitazone Add-on to Metformin in Type 2 Diabetes (SENSITIZE INDIA).

BACKGROUND: The efficacy and safety of lobeglitazone sulfate has been reported only in the Korean population, and no study has been conducted in India. MATERIALS AND METHODS: In this 16-week randomized, double-blind, and multicenter study, the efficacy and safety of lobeglitazone sulfate 0.5 mg were evaluated with pioglitazone 15 mg. Type 2 diabetes mellitus (T2DM) patients with ≥7.5% glycated hemoglobin (HbA1c) ≤10.5% and on stable metformin dose were assigned to both treatment arms. The primary outcome was a mean change in HbA1c. Safety assessments included adverse events (AE), home-based glucose monitoring, vital parameters, electrocardiogram (ECG), and laboratory assessments. RESULTS: A total of 328 subjects were randomized equally in two groups. A statistically significant reduction in HbA1c at week 16 in the lobeglitazone group with the least square (LS) mean change: 1.01 [standard error (SE): 0.09] (p < 0.0001) was seen. The LS mean difference between the two groups was 0.05 (SE: 0.12) [95% confidence interval (CI): -0.18, 0.27], which was statistically significant (p = 0.0013). Statistically significant reductions were also observed in fasting and postprandial glucose. Treatment-emergent Aes (TEAE) were comparable between both groups. CONCLUSION: Lobeglitazone 0.5 mg once daily was found to be efficacious and safe in the treatment of T2DM in the Indian population. Lobeglitazone significantly improved glycemic parameters and was noninferior to pioglitazone; hence, it could be a promising insulin sensitizer in T2DM management in India.

Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

BACKGROUND: Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. METHODS: A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. RESULTS: A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. CONCLUSION: A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Genomic revolution: Transforming tuberculosis diagnosis and treatment with the use of Whole Genome Sequencing - A consensus statement.

Tuberculosis (TB) is a preventable, treatable, and curable disease. However, in 2020, 9∙9 million people were estimated to have developed tuberculosis, and 1.5 million people were estimated to have died from it. Whereas in India, 2.6 million were diagnosed with TB and 436,000 succumbed to TB in 2019. India (26%) is the major contributor to the global drop in TB cases. The COVID-19 pandemic has substantially reduced access to services for the diagnosis and treatment of TB, resulting in an increase in deaths and a reversal in global progress. [1] Presently, TB incidence is falling at a rate of 2% per year, obstructed mainly by the rearing pandemic of drug-resistant tuberculosis (DRTB). Particularly concerning is multi-drug resistant TB (MDRTB), defined as resistance towards isoniazid (INH) and rifampicin (RIF). [2] The World Health Organization (WHO) targeted to reduce worldwide TB incidence by 90% until 2035. (1) Early initiation of effective treatment based on susceptibility patterns of the Mycobacterium tuberculosis complex (MTBC) is considered key to successful TB control in countries with high DRTB incidence. Worldwide MDRTB treatment outcomes are poor, with cure rates less than 60% (2) due to the lack of comprehensive Drug Susceptibility Testing (DST) in most high MDRTB burden countries. This is leading to the inadequate anti-TB activity of the provided regimens (3-5), unlike regimens advised for DST assure optimal results. (6) In addition to resistances to the established regimens, the resistance to the newer DRTB drugs is increasing. On World TB Day 2022, Academy of Advanced Medical Education, Thyrocare Technologies Limited and HyastackAnalytics - IITB along with expert pulmonologist and renowned physicians from India convened for an advisory board meeting in Delhi on 20th March 2022 to discuss the role of Whole Genome Sequencing (WGS) in the diagnosis and management of TB. Objectives and specific topics relating to WGS in MDRTB were discussed, each expert shared their views, which led to a group discussion with a commitment to putting the patient first, and increasing their collective efforts, the organizations recognized that it is possible to make this goal a reality. The organizations involved in the discussion have declared their commitment to engaging in collaborative efforts to tackle DRTB detection efficiently. They advocate for strengthening access to WGS TB services, controlling and preventing TB, improving surveillance and drug resistance management, and investing in research and development. This Round Table serves as a framework to build on and ensure that the goal of ending TB is achievable with WGS services wherever needed. Post discussion, a uniform consensus was said to be arrived if more than 80% board members agreed to the statement. The present paper is the outcome of aspects presented and discussed in the advisory board meeting.

Digital Twin-Enabled Personalized Nutrition Improves Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes: Results of a 1-Year Randomized Controlled Study.

OBJECTIVE: Postprandial hyperglycemia drives insulin resistance and inflammation, leading to metabolic dysfunction-associated fatty liver disease (MAFLD). Prediction of postprandial glycemic responses by digital twin (DT) technology can fashion a personalized nutrition, activity, and sleep to treat type 2 diabetes (T2D) and MAFLD. This study examines the effects of DT-enabled personalized nutrition, activity, and sleep on glycemic status, surrogate markers of MAFLD, and magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with T2D. METHODS: In an open-label randomized trial (2:1), 319 people with T2D were eligible to intervention (DT) or standard care (SC). DT patients followed personalized meal plans with foods suggested by artificial intelligence with least predicted postprandial glycemic response. The primary end point was to compare change in hemoglobin A1c (HbA1c) and medicine reduction between the DT and SC groups. Key secondary end points included remission to compare liver function test scores and visceral adiposity using MRI. RESULTS: HbA1C was significantly better for DT than for SC (-2.9 [1.8] vs -0.3 [1.2]; P < .001) at 1 year with 72.7% remission of T2D. In patients with abnormal baseline values, significant improvements were seen in DT vs SC patients from baseline to 1 year in nonalcoholic fatty liver disease liver fat score (mean [SD]; -2.5 [2.0] vs -0.1 [1.5]; P < .001) and nonalcoholic fatty liver disease fibrosis score (-1.20 [0.9] vs -0.1 [1.0]; P < .001), respectively. Improvements are seen with DT compared with SC in other liver fat, fibrosis score, and %liver fat by MRI-PDFF. CONCLUSION: At 1 year, DT-enabled personalized treatment significantly improved hyperglycemia and surrogate markers of MAFLD and MRI-PDFF.

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH). METHODS: PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcome was the change in the serum alanine transaminase level. The secondary outcomes were changes in liver stiffness, liver function test parameters, metabolic parameters, and safety. Pooled mean differences and relative risks were calculated using random-effects models. RESULTS: Six hundred studies were screened and eight were included (n = 2413). Semaglutide treatment showed a reduction in serum alanine transaminase [mean difference: 14.07 U/L (95% CI: 19.39 to -8.75); p < 0.001] and aspartate transaminase [mean difference: 6.89 U/L (95% CI: 9.14 to -4.63); p < 0.001] levels. There was a significant improvement in liver fat content [mean difference: 4.97% (95% CI: 6.65 to -3.29); p < 0.001] and liver stiffness [mean difference: 0.96 kPa (95% CI: 1.87 to -0.04); p = 0.04]. There were significant improvements in the glycated hemoglobin level and the lipid profile. However, the risk of serious adverse events [relative risk: 1.54 (95% CI: 1.02 to 2.34); p = 0.04] was high following semaglutide treatment as compared to placebo; the most common ones were gastrointestinal (nausea and vomiting, dyspepsia, decreased appetite, constipation, and diarrhea) and gallbladder-related diseases. CONCLUSION: Treatment with 24 weeks of semaglutide could significantly improve liver enzymes, reduce liver stiffness, and improve metabolic parameters in patients with NAFLD/NASH. However, the gastrointestinal adverse effects could be a major concern.

A scoping review of social media in child, adolescents and young adults: research findings in depression, anxiety and other clinical challenges.

BACKGROUND: Social media and other technologies are reshaping communication and health. AIMS: This review addresses the relationship between social media use, behavioural health conditions and psychological well-being for youth aged <25 years. METHOD: A scoping review of 11 literature databases from 2000 to 2020 explored research studies in youth in five areas: clinical depression and anxiety, quantitative use, social media mode, engagement and qualitative dimensions and health and well-being. RESULTS: Out of 2820 potential literature references, 140 met the inclusion criteria. The foci were clinical depression and anxiety disorders (n = 78), clinical challenges (e.g. suicidal ideation, cyberbullying) (n = 34) and psychological well-being (n = 28). Most studies focused on Facebook, Twitter, Instagram and YouTube. Few studies are longitudinal in design (n = 26), had comparison groups (n = 27), were randomised controlled trials (n = 3) or used structured assessments (n = 4). Few focused on different youth and sociodemographic populations, particularly for low-income, equity-seeking and deserving populations. Studies examined association (n = 120; 85.7%), mediating (n = 16; 11.4%) and causal (n = 4; 2.9%) relationships. Prospective, longitudinal studies of depression and anxiety appear to indicate that shorter use (≤3 h/day) and purposeful engagement is associated with better mood and psychological well-being. Depression may predict social media use and reduce perception of support. Findings provide families, teachers and providers ways to engage youth. CONCLUSIONS: Research opportunities include clinical outcomes from functional perspective on a health continuum, diverse youth and sociodemographic populations, methodology, intervention and privacy issues. More longitudinal studies, comparison designs and effectiveness approaches are also needed. Health systems face clinical, training and professional development challenges.

Insulin Tregopil: An Ultra-Fast Oral Recombinant Human Insulin Analog: Preclinical and Clinical Development in Diabetes Mellitus.

Insulin therapy is indispensable for achieving glycemic control in all patients with type 1 diabetes mellitus and many patients with type 2 diabetes mellitus. Insulin injections are associated with negative connotations in patients owing to administration discomfort and adverse effects such as hypoglycemia and weight gain. Insulin administered orally can overcome these limitations by providing a convenient and effective mode of delivery with a potentially lower risk of hypoglycemia. Oral insulin mimics the physiologic process of insulin secretion, absorption into the portal circulation, and subsequent peripheral delivery, unlike the subcutaneous route that results in peripheral hyperinsulinemia. Insulin tregopil (IN-105), a new generation human recombinant insulin, methoxy (polyethylene glycol) hexanoyl human recombinant insulin, is developed by Biocon as an ultra-fast onset short-acting oral insulin analog. This recombinant oral insulin is a single short-chain amphiphilic oligomer modified with the covalent attachment of methoxy-triethylene-glycol-propionyl moiety at Lys-ß29-amino group of the B-chain via an amide linkage. Sodium caprate, an excipient in the insulin tregopil formulation, is a permeation enhancer that increases its absorption through the gastrointestinal tract. Also, meal composition has been shown to non-significantly affect its absorption. Several global randomized, controlled clinical trials have been conducted in type 1 and type 2 diabetes patients towards the clinical development of insulin tregopil. The formulation shows post-prandial glucose control that is more effective than placebo throughout the meal period; however, compared with an active comparator insulin aspart, the post-prandial control is more effective mainly in the early post-meal period. It shows a good safety profile with a lower incidence of clinically significant hypoglycemia. This review covers the overall clinical development of insulin tregopil establishing it as an ultra-fast onset, short-acting oral insulin analog for optimizing post-prandial glucose.

The LongitudinAl Nationwide stuDy on Management And Real-world outComes of diabetes in India over 3 years (LANDMARC trial).

INTRODUCTION: LANDMARC (CTRI/2017/05/008452), a prospective, observational real-world study, evaluated the occurrence of diabetes complications, glycemic control and treatment patterns in people with type 2 diabetes mellitus (T2DM) from pan-India regions over a period of 3 years. METHODS: Participants with T2DM (≥25 to ≤60 years old at diagnosis, diabetes duration ≥2 years at the time of enrollment, with/without glycemic control and on ≥2 antidiabetic therapies) were included. The proportion of participants with macrovascular and microvascular complications, glycemic control and time to treatment adaptation over 36 months were assessed. RESULTS: Of the 6234 participants enrolled, 5273 completed 3 years follow-up. At the end of 3-years, 205 (3.3%) and 1121 (18.0%) participants reported macrovascular and microvascular complications, respectively. Nonfatal myocardial infarction (40.0%) and neuropathy (82.0%) were the most common complications. At baseline and 3-years, 25.1% (1119/4466) and 36.6% (1356/3700) of participants had HbA1c <7%, respectively. At 3-years, population with macrovascular and microvascular complications had higher proportion of participants with uncontrolled glycemia (78.2% [79/101] and 70.3% [463/659], respectively) than those without complications (61.6% [1839/2985]). Over 3-years, majority (67.7%-73.9%) of the participants were taking only OADs (biguanides [92.2%], sulfonylureas [77.2%] and DPP-IV inhibitors [62.4%]). Addition of insulin was preferred in participants who were only on OADs at baseline, and insulin use gradually increased from 25.5% to 36.7% at the end of 3 years. CONCLUSION: These 3-year trends highlight the burden of uncontrolled glycemia and cumulative diabetes-related complications, emphasizing the importance of optimizing diabetes management in India.