Comparative outcomes of systemic diseases in people with type 2 diabetes, or obesity alone treated with and without GLP-1 receptor agonists: a retrospective cohort study from the Global Collaborative Network : Author list.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to manage type 2 diabetes (T2D) and obesity. Despite their recognized benefits in glycemic control and weight management, their impact on broader systemic has been less explored. OBJECTIVE: This study aimed to evaluate the impact of GLP-1RAs on a variety of systemic diseases in people with T2D or obesity. METHODS: We conducted a retrospective cohort study using data from the Global Collaborative Network, accessed through the TriNetX analytics platform. The study comprised two primary groups: individuals with T2D and those with obesity. Each group was further divided into subgroups based on whether they received GLP-1RA treatment or not. Data were analyzed over more than a 5-year follow-up period, comparing incidences of systemic diseases; systemic lupus erythematosus (SLE), systemic sclerosis (SS), rheumatoid arthritis (RA), ulcerative colitis (UC), crohn's disease (CD), alzheimer's disease (AD), parkinson's disease (PD), dementia, bronchial asthma (BA), osteoporosis, and several cancers. RESULTS: In the T2D cohorts, GLP-1RA treatment was associated with significantly lower incidences of several systemic and metabolic conditions as compared to those without GLP-1RA, specifically, dementia (Risk Difference (RD): -0.010, p < 0.001), AD (RD: -0.003, p < 0.001), PD (RD: -0.002, p < 0.001), and pancreatic cancer (RD: -0.003, p < 0.001). SLE and SS also saw statistically significant reductions, though the differences were minor in magnitude (RD: -0.001 and - 0.000 respectively, p < 0.001 for both). Conversely, BA a showed a slight increase in risk (RD: 0.002, p < 0.001). CONCLUSIONS: GLP-1RAs demonstrate potential benefits in reducing the risk of several systemic conditions in people with T2D or obesity. Further prospective studies are needed to confirm these effects fully and understand the mechanisms.

Genetic polymorphism of fatty acid binding protein-2 in hyperlipidemic Asian Indians in North India.

BACKGROUND: Fatty acid binding protein-2 (FABP-2) is involved in the metabolism of lipids in the intestine. FABP-2 Ala54Thr polymorphism involves a transition of G to A at codon 54 of FABP-2, resulting in an amino acid substitution Ala54 to Thr54 and is associated with elevated fasting triglycerides in some hyperlipidemic populations. In current genome builds and gene databases the variant of the Ala54Thr FABP-2 (rs 1 799 883) is annotated as c.163A>G (p. Thr55Ala). AIM AND OBJECTIVE: The status of this polymorphism in hyperlipidemic Asian Indians from North India has not been investigated. This study was aimed to evaluate the distribution of the polymorphic variants of the Ala54Thr FABP-2 and their association with lipids in hyperlipidemic subjects. METHODS: Ala54Thr FABP-2 polymorphism in both hyperlipidemic (n = 210) and normolipidemic (n = 342) subjects was assessed by PCR-RFLP. RESULTS: Ala54Thr genotypes and alleles distribution did not differ between the hyperlipidemic and normolipidemic groups. The heterozygous genotype FABP-2 Ala/Thr was significantly associated with higher levels of triglycerides and very low-density lipoproteins as compared to the homozygous variant (Thr/Thr) genotype and the wild type homozygous (Ala/Ala) genotype. CONCLUSIONS: The heterozygous genotype FABP-2 Ala54Thr is a risk factor for the development of hypertriglyceridemia and increased levels of VLDL-c in Asian Indians from North India.

Role and Significance of Dietary Protein in the Management of Type 2 Diabetes and Its Complications in India: An Expert Opinion.

BACKGROUND: Obesity, prediabetes, and type 2 diabetes mellitus (T2DM) pose a triple burden in India. Almost two-thirds of people with diabetes (PWD) in India are found to have suboptimal glycemic, blood pressure, and lipid control. Medical nutrition therapy (MNT) in diabetes has emphasized on the amount and type of carbohydrates for years. However, protein, an important macronutrient in diabetes management, needs to be focused upon, especially in India, where the consumption is found to be lower than the recommendations provided by most guidelines. AIM: An expert committee attempted to review the role of dietary protein in the management of T2DM, arrive at a consensus on the significance of increasing dietary protein for various benefits, and offer practical guidance on ways to improve protein intake among Indians. METHODOLOGY: A total of 10 endocrinologists and diabetologists, one nephrologist, and three registered dietitians representing four zones of India formed the expert committee. An in-depth review of literature in the Indian context was carried out, and the draft document was shared with the expert committee, and their views were incorporated into the same. The expert committee then assembled virtually to deliberate on various aspects of the role of protein in T2DM management. The experts from various specialties gave their valuable inputs and suggestions from their extensive personal clinical experience and research work, which helped to reach a consensus on the role and significance of protein in the management of T2DM and its complications in India. RESULTS: There is abundant evidence that MNT is essential for the prevention and management of T2DM and its complications. Experts agreed that increasing protein intake offers myriad health benefits, namely reducing glycemic variability, improving glycemic control, increasing insulin sensitivity, improvement in lipid profile and immunity, and helping in weight management and preservation of muscle mass in PWD. The expert committee suggested aiming for an increase in protein intake by at least 5-10% of the current intake in lieu of carbohydrates in PWD. Experts also highlighted the need for more data quantifying the unmet protein needs in the Indian PWD, especially among vegetarians. Randomized controlled trials to study the effect of protein in diabetes complications such as cardiovascular disease (CVD) and diabetic kidney disease (DKD) and comorbid conditions such as sarcopenia among the Indian population are also warranted. CONCLUSION: Increasing protein quantity and quality in the diets of Indian PWD could significantly contribute to positive health outcomes. Increased protein intake, preferably through dietary sources to meet the requirements and, when required using diabetes-specific protein supplements (DSPS), is recommended in the prevention and control of T2DM.

SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

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 (ß-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 ß-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.

Management of Hyperglycemia in COVID-19 and Post-COVID-19 Syndrome - Proposed Guidelines for India.

SARS-CoV-2 virus spread rapidly all over the globe in 2020 and the second wave has taken our nation, India by storm. The pandemic has posed unique challenges in people with metabolic disorders, including diabetes, hypertension, obesity, pulmonary, cardiovascular, kidney and non-alcoholic fatty liver disease. Uncontrolled diabetes, in conjunction with endocrine, inflammatory and metabolic effects of the infection itself has made management of hyperglycemia in COVID-19 infection particularly challenging. Furthermore, the post-COVID-19 syndrome has also emerged as a sequela in COVID-19 survivors, increasing the risk of death, complications and adding further burden on the health care system. With more than a year of experience, we have gained substantial insight; and now provide practical recommendations on the management of hyperglycemia in COVID-19 as well as post COVID-19 syndrome.

The impact of obesity on inflammatory markers used in the assessment of disease activity in rheumatoid arthritis - a cross-sectional study.

INTRODUCTION: Obesity is known to be associated with elevated levels of inflammatory markers. The aim of the study was to assess the confounding effect of obesity on the levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients with rheumatoid arthritis (RA) in low disease activity state or remission as indicated by clinical disease activity index (CDAI). MATERIAL AND METHODS: Adult RA patients with CDAI less than 10 were divided into two groups: obese and non-obese, based on body mass index. Relevant exclusions were applied to eliminate causes of raised inflammatory markers other than obesity. The difference of CRP and ESR levels between the obese and non-obese groups was analyzed. RESULTS: Obese patients with RA (n = 85) had higher CRP and ESR than non-obese patients (n = 66) (p-values 0.008 and 0.000005, respectively). In addition, obese females with RA had significantly higher CRP and ESR as compared to non-obese females. However, the difference was not significant in males. Twenty-one obese (24.7%) and two non-obese RA patients (3%) had elevated CRP (difference of approximately 22% [24.7 minus 3]). Forty obese (47%) and 16 non-obese RA patients (24.2%) had elevated ESR (difference of approximately 23% [47 minus 24.2]). Thus, obesity was the attributable cause of falsely elevated CRP and ESR in 22% and 23% of patients, respectively. CONCLUSIONS: About one-fifth of patients with RA, who are actually in low disease activity, may have elevated inflammatory markers, primarily because of obesity. Therefore, elevated CRP and ESR in obese patients with RA should be interpreted with caution because it may lead to unnecessary overtreatment.

Effect of high-protein meal replacement on weight and cardiometabolic profile in overweight/obese Asian Indians in North India.

The aim of the present study was to evaluate the impact of a high-protein meal replacement (HPMR) on weight and metabolic, lipid and inflammatory parameters in overweight/obese Asian Indians. In this 12-week open-label, parallel-arm randomised controlled trial, 122 overweight/obese men and women were administered either a HPMR or a control diet after 2 weeks of diet and exercise run-in. Body weight, waist circumference (WC), percentage body fat (%BF), fasting blood glucose, post-oral glucose tolerance test (post-OGTT) blood glucose, fasting and post-OGTT serum insulin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), kidney function and hepatic aminotransferases were assessed before and after the intervention. Additional improvement in mean values for the following parameters in the HPMR group compared with the control group was observed: body weight, 4·9 % (95 % CI 3·8, 6·1; P<0·001); WC, 3·8 % (95 % CI 2·5, 5·1; P<0·001); %BF, 6·3 % (95 % CI 4·3, 8·2; P<0·001); systolic blood pressure, 2·8 % (95 % CI 0·4, 5·1; P=0·002); diastolic blood pressure, 3·5 % (95 % CI 0·7, 6·3; P= 0·01); post-OGTT blood glucose, 7·3 % (95 % CI 1·4, 13·1; P=0·02); total cholesterol, 2·5 % (95 % CI 1·6, 3·5; P<0·001); LDL-cholesterol, 7·3 % (95 % CI 1·7, 12·9; P<0·01); alanine aminotransferase, 22·0 % (95 % CI 2·1, 42; P=0·03) and aspartate aminotransferase, 15·2 % (95 % CI 0·9, 29·5; P=0·04). The absolute reduction in BMI was 0·9 units in the intervention arm compared with the control arm (-0·9 %, 95 % CI -1·4, -0·5; P<0·001) and in serum TAG was 11·9 mg/dl (-11·9 mg/dl, 95 % CI -21·1, -2·7; P<0·01). The reduction in fasting serum insulin in the intervention v. the control arm was 3·8 v. 0 % (P=0·002); post-OGTT serum insulin was 50·3 v. 77·3 mU/l (P=0·005); and hs-CRP, 16·7 % v. 0 % (P=0·002). These findings show that intervention with HPMR may lead to significant weight loss and improvement in obesity measures, metabolic, lipid and inflammatory parameters and hepatic transaminases in overweight/obese Asian Indians.

Effects of 3 g of soluble fiber from oats on lipid levels of Asian Indians - a randomized controlled, parallel arm study.

BACKGROUND: Cardiovascular diseases are more prevalent and severe in Asian Indians. Simple diet-based strategies are important for prevention of cardiovascular diseases.The aim of the present study was to evaluate the effects of oats consumption on lipid parameters in mildly hypercholesterolemic Asian Indians living in India. METHODS: A short-term, prospective, open-labeled, randomized controlled, parallel group study was conducted. Mildly hypercholesterolemic (total cholesterol >200 mg/dL and <240 mg/dL) subjects (n = 80) were randomized into two groups: intervention (n = 40) and usual diet (n = 40). Sample size was calculated for a two-group parallel superiority randomized control trial. Out of 80 enrolled subjects 69 subjects completed the study; 33 in the control group and 36 in the intervention group. In the intervention group, patients were served 70 g of oats twice a day in the form of porridge and upma (A thick porridge from oats with seasonings and vegetables) under observation at the study site. Lipid parameters were assessed at baseline and after 4 weeks of intervention. RESULTS: There was a reduction of 3.1% in total cholesterol levels in the control group as against 8.1% reduction in the intervention group (p < 0.02). Greater reductions were also seen in low-density lipoprotein cholesterol in the intervention group (11.6%) as compared to control group (4.1%, p < 0.04) over a period of 28 days. CONCLUSION: Daily consumption of 3 g of soluble fiber from 70 g of oats leads to beneficial effects on the lipid parameters, specifically total cholesterol and low-density lipoprotein cholesterol in hypercholesterolemic Asian Indians. Large scale studies over a longer period of intervention are required to further establish the cholesterol-lowering effect of oat fiber. TRIAL REGISTRATION: The study was retrospectively registered at clinicaltrials.gov (dated: 25th Februrary.2015) with registration number NCT02376660 .

Effect of oral cinnamon intervention on metabolic profile and body composition of Asian Indians with metabolic syndrome: a randomized double -blind control trial.

BACKGROUND: Nutritional modulation remains central to the management of metabolic syndrome. Intervention with cinnamon in individuals with metabolic syndrome remains sparsely researched. METHODS: We investigated the effect of oral cinnamon consumption on body composition and metabolic parameters of Asian Indians with metabolic syndrome. In this 16-week double blind randomized control trial, 116 individuals with metabolic syndrome were randomized to two dietary intervention groups, cinnamon [6 capsules (3 g) daily] or wheat flour [6 capsules (2.5 g) daily]. Body composition, blood pressure and metabolic parameters were assessed. RESULTS: Significantly greater decrease [difference between means, (95% CI)] in fasting blood glucose (mmol/L) [0.3 (0.2, 0.5) p = 0.001], glycosylated haemoglobin (mmol/mol) [2.6 (0.4, 4.9) p = 0.023], waist circumference (cm) [4.8 (1.9, 7.7) p = 0.002] and body mass index (kg/m2 ) [1.3 (0.9, 1.5) p = 0.001] was observed in the cinnamon group compared to placebo group. Other parameters which showed significantly greater improvement were: waist-hip ratio, blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, and high-density lipoprotein cholesterol. Prevalence of defined metabolic syndrome was significantly reduced in the intervention group (34.5%) vs. the placebo group (5.2%). CONCLUSION: A single supplement intervention with 3 g cinnamon for 16 weeks resulted in significant improvements in all components of metabolic syndrome in a sample of Asian Indians in north India. TRIAL REGISTRATION: The clinical trial was retrospectively registered (after the recruitment of the participants) in ClinicalTrial.gov under the identification number: NCT02455778 on 25th May 2015.

Vitamin D status of adult females residing in Ballabgarh health and demographic surveillance system: A community-based study.

BACKGROUND: Vitamin D deficiency (VDD) is widespread, yet it is the most underdiagnosed and undertreated nutritional deficiency in the world. The prevalence of VDD is estimated to affect over 1 billion people worldwide. OBJECTIVES: The present study was conducted to estimate the prevalence of VDD among adult females aged 20-60 years residing in a rural community of North India, and to find its association with various sociobehavioral risk factors. METHODS: The present study is an analytical cross-sectional study conducted among females aged 20-60 years in rural Ballabgarh. Four hundred women were randomly selected from one of the villages of the Health and Demographic Surveillance System. Semi-structured, pretested interview schedule was administered to the study participants. Fasting venous blood sample was collected for the measurement of plasma sugar level and Vitamin D (25-hydroxyvitamin D). RESULTS: The prevalence of VDD was 90.8% (95% confidence interval [CI] - 87.5-93.3), while that of Vitamin D insufficiency was 8.9% (95% CI - 6.4-12.2). On logistic regression analysis, 24 h calorie intake, protein intake, and prediabetes status of the participants were significantly associated with VDD. CONCLUSION: Very high prevalence of VDD was observed among the females (20-60 years) residing in rural Ballabgarh.

Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

OBJECTIVE: Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. METHODS: Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. RESULTS: Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P<.001). Target HbA1c of <7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm. CONCLUSION: Patient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

Impact of treatment with GLP-1RAs on suicide attempts in adults persons with type 2 diabetes: A retrospective comparative effectiveness study based on a global TriNetX health research database.

OBJECTIVE: To assess the association between glucagon-like peptide-1 receptor agonists (GLP-1RA) treatment and the risk of suicide attempts in people with type 2 diabetes (T2D), with a focus on subgroups with and without a history of depression or suicide attempts. METHODS: This retrospective cohort study utilized TriNetX, a federated network of real-world data. Using the Global Collaborative Network data, we collected electronic medical records from 113 health care organizations with 135 million patient records with 8 million with T2D, 83% from the United States. The four cohorts were identified based on age, medication, diagnosis, and presence of depression or suicide attempts. Analytic methods included measures of association and number of Instances, with propensity score matching employed to mitigate potential confounders. The primary outcome was the incidence of suicide attempts among people with T2D with GLP-1RA treatment in comparison with dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment. RESULTS: People with T2D treated with GLP-1RA consistently exhibited a lower risk of suicide attempts compared to those treated with DPP-4i. This was particularly significant in people with a history of depression or suicide attempts. The risk and odds ratios were significantly lower in the GLP-1RA-treated cohorts than in DPP-4i across all analyses. CONCLUSION: As compared with DPP-4i, our analysis shows a protective effect associated with GLP-1RA treatment on the risk of suicide attempts among people with T2D. However, further research, particularly prospective and randomized studies, is necessary to confirm these observations and understand the underlying mechanisms.

Decreased risk of recurrent acute pancreatitis with semaglutide and tirzepatide in people with type 2 diabetes or obesity with a history of acute pancreatitis: A propensity matched global federated TriNetX database-based retrospective cohort study.

BACKGROUND: Acute pancreatitis (AP) is a significant health concern with potential for recurrent episodes and serious complications. The risk of recurrence in type 2 diabetes (T2D) or obesity can be influenced by various factors and treatments, including GLP-1 receptor agonists (GLP-1RAs). This study evaluates the risk of recurrent AP among patients with a history of the condition, focusing on the effects of different GLP-1RA treatments. OBJECTIVES: Our objective is to compare the recurrence risks of AP between patients treated with different GLP-1RAs. METHODS: We conducted a retrospective cohort study using the TriNetX platform, encompassing 258,238 individuals with T2D or obesity who have a history of AP. We assessed the recurrence of AP over a five-year period, analyzing data on treatment regimens, with a focus on the use of Semaglutide, Tirzepatide, and other GLP-1RAs. RESULTS: GLP-1RA users experienced significantly lower recurrence rates of AP, with those without risk factors showing GLP-1RA users had a recurrence rate of 13.8 % compared to 40.9 % for non-users. Semaglutide and Tirzepatide showed the most favorable outcomes; Semaglutide users had lower recurrence rates than Exenatide (10.1 % vs. 27 %) and slightly lower than Dulaglutide (13.6 % vs. 15.4 %), though not statistically significant with Dulaglutide. Tirzepatide users displayed the lowest recurrence risk at 6.2 %, significantly lower than those on Semaglutide (11.7 %). CONCLUSIONS: GLP-1RAs, particularly Semaglutide and Tirzepatide, are associated with a reduced risk of recurrent AP in people with T2D or obesity. The differential risk profile between these drugs highlights the need for further studies and personalized treatment plans.

Efficacy and safety of oral semaglutide in type 2 diabetes: A systematic review of real-world evidence.

BACKGROUND AND AIMS: Oral semaglutide has undergone global Phase 3 development programs named PIONEER and approved for therapeutic use in people with type 2 diabetes (T2D). We aim to systematically review the efficacy and safety of oral semaglutide in real-world settings. METHODS: We systematically searched the electronic databases of PubMed, Google Scholar, and ClinicalTrials.gov from inception until March 15, 2024, using several keywords with Boolean "AND". We retrieved all the available granular details of real-world studies (RWS). RESULTS: To date, results from four prospective and ten retrospective real-world studies of oral semaglutide in T2D are available. In prospective studies, the primary outcome of HbA1c reduction varied from -0.9 % to -1.6 %, weight loss varied from -4.7 kg to -8.2 kg and HbA1c target of <7 % was achieved in 30 %-64 % with oral semaglutide. In retrospective studies, HbA1c reduction varied from -0.4 % to -1.8 %, weight reduction varied from -1.4 to -9.0 kg, HbA1c target of <7 % was achieved in 32-64 %, and 30-41 % of people with T2D had ≥5 % weight loss with oral semaglutide. Gastrointestinal adverse events with oral semaglutide varied from 16 % to 50 % in prospective and 6 %-47 % in retrospective RWS. Overall, 0 %-18 % of patients had oral semaglutide discontinuation due to any cause. CONCLUSION: Oral semaglutide exhibited a reasonable reduction in HbA1c and weight in people with T2D, consistent with the findings from PIONEER trials. While no new safety issues emerged, the inherent limitations of RWS underscore the necessity of long-term investigations to comprehensively assess safety.

Intrahepatic hypothyroidism in MASLD: Role of liver-specific thyromimetics including resmetirom.

BACKGROUND AND AIMS: Thyroid hormones are important regulators of hepatic lipid homeostasis and whole-body energy expenditure. Recent evidence suggests that euthyroid individuals with metabolic dysfunction-associated steatohepatitis (MASH) develop intrahepatic hypothyroidism that promotes progression of MASH. METHODS: A literature search was performed with Medline (PubMed), Scopus and Google Scholar electronic databases from inception till March 2024, using the following keywords: hypothyroidism and nonalcoholic fatty liver disease; MASLD and thyroid function; intrahepatic hypothyroidism; TRß agonists; and resmetirom. Relevant studies were extracted that described pathogenesis of MASH in the context of thyroid functions. RESULTS: In euthyroid individuals with MASH, there is decreased conversion of prohormone thyroxine (T4) to bioactive tri-iodothyronine (T3) and increased conversion of T4 to inactive metabolite reverse T3 (rT3). Consequently, reduced levels of T3 results in impaired intrahepatic TRß signaling, a state of intrahepatic hypothyroidism, which promotes progression of MASH. Hepatic TRß activation leads to metabolically beneficial effects in the liver including mitochondrial fatty acid uptake and ß-oxidation, mitochondrial biogenesis, increasing surface low-density lipoprotein (LDL) receptor density and lowering of circulatory LDL-cholesterol. In recent years, selective thyroid hormone mimetics that exhibit TRß-selective binding and liver-selective uptake have been designed. Resmetirom, a liver-specific thyromimetic, improves intrahepatic TRß signaling and in clinical trials significantly improved liver inflammation, fibrosis and lipid profile in patients with MASH. CONCLUSIONS: In euthyroid individuals with MASH, development of intrahepatic hypothyroidism results in further progression of the disease. In clinical trials, resmetirom treatment results in a significant improvement in steatosis, inflammation and fibrosis and is the first drug approved by the US Food and Drug Administration (FDA) for the treatment of noncirrhotic MASH with moderate to advanced fibrosis.

Hand grip strength as a proposed new vital sign of health: a narrative review of evidences.

Hand grip strength (HGS) serves as a fundamental metric in assessing muscle function and overall physical capability and is particularly relevant to the ageing population. HGS holds an important connection to the concept of sarcopenia, which encompasses the age-related decline in muscle mass, strength, and function. It has also been reported to indicate the health of an individual. We reviewed the interplay between HGS and various health parameters, including morbidity and mortality, by carrying out a literature search on PubMed, Scopus and Google Scholar between 10 and 30 August 2023, to identify the relevant papers on the relationship between health and HGS. We used several keywords like 'hand grip strength', 'muscle strength, 'sarcopenia', 'osteosarcopenia', 'health biomarker', 'osteoporosis', and 'frailty', to derive the appropriate literature for this review. This review has shown that the HGS can be measured reliably with a hand-held dynamometer. The cut-off values are different in various populations. It is lower in Asians, women, less educated and privileged, and those involved in sedentary work. Several diseases have shown a correlation with low HGS, e.g., Type 2 diabetes, cardiovascular disease, stroke, chronic kidney and liver disease, some cancers, sarcopenia and fragility fractures. The low HSG is also associated with increased hospitalization, nutritional status, overall mortality and quality of life. We believe that there is adequate evidence to show that HGS stands as an important biomarker of health. Its utility extends to the identification of diverse health issues and its potential as a new vital sign throughout the lifespan.

Scientometric analysis of global publications on prediabetes and osteoporosis: 1994-2023.

Background and aims: Prediabetes and osteoporosis are two commonly prevalent diseases that can have interconnected implications for overall well-being. There is a paucity of literature on "prediabetes and osteoporosis". We aimed to assess the current state of cross-sectional studies involving osteoporosis and prediabetes as well as their bibliometric features. Methods: Publications about prediabetes and osteoporosis between January 1994 and November 2023 were taken from the Scopus database, and VOSviewer and Microsoft Office Excel were used for bibliometric analysis and visualization. Results: We identified 272 documents that were written by 531 authors from 48 countries including 252 organizations. The USA was the leading country with the highest publications (n = 84) and Canada had the largest citation impact per paper (109.0). University of California, San Francisco contributed the most publications (n = 6), while Universita degli Studi di Torino, Italy (275.0 and 5.25), had the highest citation impact. Frontiers in Endocrinology (n = 7), was the most productive journal, while Annals of Internal Medicine (322.0) was the most influential in terms of citation impact per paper. The funded research was 30.5 %, while 17.6 % of research were involved in international collaboration. Conclusion: The number of publications on this topic has increased over three decades. The highest citations per paper were received by the publications which had external funding, followed by those which had international collaboration. All the highly cited papers were published from high-income countries.

Research on Non-alcoholic Fatty Liver Disease From Indian Subcontinent: A Bibliometric Analysis of Publications During 2001-2022.

Introduction: The non-alcoholic fatty liver disease (NAFLD) is common in the Indian Subcontinent. We aimed to examine the bibliometric characteristics of the publications arising from the countries of the Indian Subcontinent on NAFLD, over the last two decades. Methods: Publications on NAFLD from Indian Subcontinent during the period of 2001-2022 were retrieved from the Scopus database. Various important bibliometric parameters were studied from the retrieved publications and were exported to MS-Excel for analysis. VOSviewer software was used for analyzing co-author collaborative networks and keyword co-occurrence networks. Results: There is a rising trend of publications, especially in the last decade, with an average annual growth of 28.95% and an absolute growth of 526.21% between 2013 and 2022, compared to 2001-2012. From Indian Subcontinent's authors, 1053 papers were indexed in Scopus, with the majority (81.3%) being from India. Indian Subcontinent holds 13th rank globally with 3.43% share of global output. External funding was received for 15.76% publications and 24.59% papers were prepared with international collaboration, and these received much higher citations per paper. Research output is low, only 3.43% of global share. Regional research cooperation among countries of Indian subcontinent is also poor. Further, only 3.61% of papers were highly cited. Conclusion: Despite a high prevalence of NAFLD in Indian Subcontinent, the research output is low and of low impact. Further, the research collaboration between these Indian Subcontinent needs improvement.

Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.