Introduction: Postprandial glucose excursions can contribute to increased cardiovascular risk, microvascular complications, and glycaemic variability in type 2 diabetes mellitus (T2DM). Nutritional interventions play a major role. Whey protein, known for its insulinotropic and incretin-stimulating effects, could be an effective supplement. The objective of the study was to evaluate the acute effects of pre-breakfast whey protein supplementation on postprandial glucose, insulin, GLP-1, and C-peptide responses in patients with T2DM. Methods: This single-centre, prospective, within-subject comparative study included two test visits per participant: a water pre-load (control) and a whey protein pre-load (30 g in 250 mL water) given 30 min before breakfast. Uniform breakfast and lunch meals were provided, and blood samples were collected up to 2 h after lunch. Plasma glucose, insulin, GLP-1, and C-peptide were recorded, and the incremental area under the curve (iAUC) was calculated. Results: Ten patients with T2DM were studied (mean age 47.8 years, body mass index 29.2 kg/m², glycated haemoglobin 7.4%, disease duration 3.2 years). Compared with water, whey protein significantly reduced post-breakfast and post-lunch glucose excursions (glucose iAUC 48,329 vs. 54,743; P < 0.01) and increased insulin (13,377 vs. 9,492; P < 0.01), GLP-1 (18,803 vs. 12,814; P < 0.01), and C-peptide (1860 vs. 1535; P < 0.01) iAUCs. The effect persisted through the second meal. Conclusion: Pre-breakfast whey protein supplementation reduced postprandial glucose excursions and enhanced insulin and incretin responses in T2DM. It may serve as a practical and low-cost dietary approach to improve postprandial glycaemic control.
Introduction: Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes characterised by irreversible damage to the pancreatic parenchyma with intraductal calcification, progressively leading to beta-cell damage. The classical clinical presentation of FCPD is evolving, with a declining frequency of typical phenotypes and increasing involvement of individuals with normal BMI and older age at presentation. This Study evaluated the clinical and demographic profile of patients with FCPD in North Karnataka and compared the glycaemic response to pioglitazone. Methods: This was a single-centre retrospective observational study done at a tertiary care endocrinology centre. Patients with FCPD diagnosed between December 2019 and December 2024 were retrospectively analysed. Clinical characteristics, imaging and glycaemic data were collected. Patients with suboptimal glycaemic control despite insulin therapy (HbA1c >9%) were initiated on add-on pioglitazone or metformin, and within-group changes in HbA1c and daily insulin requirement over 3 months were evaluated using paired t-tests. Results: The mean age at diagnosis was 42 ± 11.97 years, with a mean diagnostic delay of 2.83 ± 1.8 years. Only 10.5% of patients were correctly diagnosed with FCPD at initial presentation. Despite receiving insulin therapy, 76.5% of patients experienced progressive weight loss, and 76.8% reported frequent hypoglycaemic episodes. Conclusion: FCPD in North Karnataka demonstrated atypical clinical features (low BMI and chronic diarrhoea) with delayed diagnosis and frequent hypoglycaemia. Glycaemic control could be optimised with short-acting insulin. Pioglitazone compared with metformin significantly improved glycaemic parameters and reduced insulin requirement, due to its effect on hepatic insulin resistance.
Introduction:Hypothyroidism is commonly managed with levothyroxine (LT4) monotherapy, the standard treatment for many decades. However, 5%-10% of patients remain symptomatic despite achieving biochemical euthyroidism on LT4 monotherapy. Liothyronine (LT3), a synthetic form of T3, was introduced in India in 2022 but faces limited adoption due to availability, cost, and lack of clear guidelines. This study aimed to assess the perceptions, clinical usage, and barriers to LT3 prescription among healthcare professionals in India. Methods:A cross-sectional, questionnaire-based study was conducted among 455 doctors attending three endocrinology updates in Delhi, Bhopal, and Rohtak. The participants completed a 19-question structured online survey assessing demographics, LT3 awareness, usage patterns, and barriers. The responses were analysed using SPSS version 20. Results:Out of 455 respondents (42.15 ± 11.41 years), 80% were males and 27.69% were endocrinologists. LT3 awareness was reported by 80%, with 52.75% reported prescribed it, most commonly for hypothyroid emergencies (40.42%), rapid symptom control (22.50%), or persistent symptoms despite biochemical euthyroidism on LT4 monotherapy (17.50%). However, the major barriers included high cost (23.52%) and limited availability (22.86%). Among prescribers, 62.08% used once-daily dosing. Also, 74.29% of participants expressed interest in further learning about LT3. Conclusion:Reported use of LT3 in India remains limited, driven by poor awareness among clinicians, cost, and availability issues. Although awareness is high among specialists, consistent guidelines, clinician education, and accessibility improvements are needed for safe and effective LT3 integration into hypothyroidism management.
Introduction:Close to 50% of patients with Graves' disease have associated ocular involvement, of which dysthyroid optic neuropathy (DON) is prevalent in 3-5% of patients. The response to intravenous glucocorticoids in DON is dependent on early diagnosis. The purpose of this study was to assess the efficacy of various radiological indices (Barrett's index, Nugent index) in predicting DON and treatment response or relapse in this population. Methods:This was a retrospective study that included patients presenting with clinically active Graves' orbitopathy (GO) between January 2005 and June 2021 to our hospital. Demographics, clinical presentation, biochemical parameters, risk factors, comorbidities, and radiology data were collected and analysed. Results:Fifty-eight orbits from 29 patients were assessed. A higher Barrett's index was associated with DON (61.4% vs 51.1%, P = 0.03), lower glucocorticoid responsiveness (63.7% vs 54.2%, P = 0.043), and the need for surgical intervention (62.85% vs 49.3%, P = 0.001). Nugent index ≥1 was significantly associated with sight-threatening GO (48.2% vs 22.2%, P = 0.02) and higher glucocorticoid requirements (54.8% vs 23.8%, P = 0.04). A cut-off of 58% for the Barrett's index (AUC 0.705, 95% CI 0.545-0.865) was suggestive of DON, with a sensitivity of 60% and a specificity of 68.8%. Conclusions:This is the first comprehensive assessment of patients with GO among Indians with active disease. The Barrett's index threshold was defined in our population to facilitate objective early identification of DON. This index shows promise for early diagnostic sub-categorisation in DON among Indians; however, its low sensitivity limits its widespread use.
Introduction:Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterised by hyperandrogenism and ovulatory dysfunction. Nonclassic congenital adrenal hyperplasia (NCCAH) is an important differential diagnosis, but its prevalence in Indian women remains unclear. Previous North Indian studies reported variable rates using less specific assays. This study aimed to determine the prevalence and clinical characteristics of NCCAH among hyperandrogenemic South Indian women with PCOS. Methods:This cross-sectional study was conducted at a tertiary care centre in South India (January 2019 to December 2022). Women aged ≥18 years meeting Androgen Excess Society criteria for PCOS were included. Hyperandrogenemia was defined as serum total testosterone >0.55 ng/ml by chemiluminescent immunoassay. All participants underwent serum steroid profiling 60 minutes after Acton Prolongatum-stimulation using liquid chromatography-tandem mass spectrometry. The serum steroid levels of women with PCOS were compared with those of healthy volunteers. Results:Of 182 screened women, 128 were diagnosed with PCOS. Acton Prolongatum-stimulated steroid profiling was performed in 120 women. Three (2.5%) were diagnosed with congenital adrenal hyperplasia (CAH)-two with classic 21α-hydroxylase deficiency (21OHD) and one with 11β-hydroxylase deficiency. All three showed severe hirsutism, clitoromegaly and severe hyperandrogenemia (>1.5 ng/ml). None were diagnosed with nonclassic 21OHD. Compared with controls, PCOS women had significantly higher testosterone and androstenedione levels with no significant difference in other steroid levels. Conclusions:NCCAH is rare among South Indian women with PCOS, whereas the simple virilising form of classic CAH may often mimic PCOS. Severe hyperandrogenism distinguishes CAH from PCOS and helps prioritise them for CAH screening.
Introduction:Metabolic syndrome (MetS) poses significant health challenges globally, with healthcare professionals facing unique occupational risks despite their medical knowledge. This study aimed to determine the prevalence of MetS and its associated predictors among doctors at a tertiary care teaching institution. Methods:A cross-sectional study was conducted among 132 doctors at a tertiary care teaching hospital in northeastern India from June 2024 to January 2025. Data were collected using a structured WHO STEPS-based questionnaire covering sociodemographic characteristics, lifestyle factors and stress levels. Anthropometric measurements and biochemical parameters were assessed using standard protocols. MetS was diagnosed using National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Results:The overall prevalence of MetS was 26.5% (n = 35), with significant male predominance (38.4% vs 11.9%, P < 0.001). Elevated waist circumference was the most prevalent component (47.7%), followed by raised systolic blood pressure (32.6%) and elevated triglycerides (25.0%). Independent predictors of MetS included male gender (adjusted odds ratio [AOR]: 3.1, 95% confidence interval [CI]: 1.2-8.3), age >40 years (AOR: 4.5, 95% CI: 1.8-11.2), married status (AOR: 6.2, 95% CI: 2.2-17.4) and consultant or faculty position versus intern (AOR: 8.9, 95% CI: 1.9-42.1). Physical inactivity was present in 82.9% of MetS-positive participants. Perceived stress was significantly associated with MetS (42.9% vs 14.5%, P = 0.010). Conclusion:One in four doctors demonstrated MetS, with male doctors over 40 years at the highest risk. These findings underscore the urgent need for comprehensive physician wellness programmes incorporating regular metabolic health screenings, stress management and targeted lifestyle interventions in healthcare institutions.
Introduction:Omentin-1 is an adipocytokine predominantly secreted by visceral adipose tissue and associated with insulin sensitivity. Altered levels of omentin-1 in type 2 diabetes mellitus (T2DM) and obesity denote a potential link with insulin resistance. Methods:Two hundred twenty-five adult males with T2DM were segregated into non-obese (n = 75), overweight (n = 75), and obese (n = 75) groups. Anthropometric, haemodynamic, and biochemical parameters, including glucose, insulin, lipid profile, and omentin-1 were measured. Insulin resistance was assessed using validated surrogate indices. Group comparisons were performed and associations were examined using correlation analysis and a prespecified multivariable linear regression model. Results:Obese subjects had higher BMI, waist-to-hip ratio, fasting glucose, HbA1c, fasting insulin, HOMA-IR, lipid fractions, and METS-IR as compared to non-obese. Serum omentin-1 levels declined progressively with increasing adiposity [non-obese 687.6 (654.1-763.2), overweight 587.6 (548.6-658.1), obese 459.3 (398.7-524.8) ng/L; P < 0.001]. Omentin-1 showed inverse correlations with BMI (γ = -0.703), waist-to-hip ratio (γ = -0.717), HOMA-IR (γ = -0.403), triglyceride-BMI index (γ = -0.695), and LDL-cholesterol (γ = -0.417), and a positive correlation with QUICKI (γ =0.403; all P < 0.001). In the multivariable model, LDL-cholesterol remained independently associated with circulating omentin-1 levels (β =2.527, P = 0.043). Conclusion:Serum omentin-1 shows an inverse association with adiposity, insulin resistance, and lipid parameters in T2DM, suggesting that omentin-1 could serve as a potential marker of an adverse cardiometabolic profile, although comprehensive studies are further warranted.
Optimum intake of calcium is fundamental for skeletal health and additionally plays a role in cardiovascular health, haemostasis, synaptic transmission, and several enzyme-driven metabolic reactions. In several countries, including India, dietary calcium intake is poor, and it is necessary to ensure adequate calcium intake for optimizing musculoskeletal health. Not many guidelines focus on regions where calcium in the diet is suboptimal, and supplementing calcium may be specially relevant. In view of this, the Endocrine Society of India (ESI) Skeletal Task Force has developed clinical practice guidelines on calcium supplementation. The statement emphasizes that food sources should be the preferred modality of meeting calcium needs, and supplements should be used when dietary intake is insufficient or when physiological demands are higher, such as in pregnancy, lactation, or after menopause. Additionally, calcium should be supplemented in bone mineral disorders, such as osteoporosis, osteomalacia, hypocalcaemic rickets, and hypoparathyroidism. Special precautions are necessary in chronic kidney disease and in the presence of renal stone disease, but safety in cardiovascular disease is reinforced unless the total intake crosses the recommended daily intake. The statement recommends ensuring vitamin D sufficiency but strongly recommends against supplementing activated forms of vitamin D except in special situations. This ESI statement aims to provide rationalized guidance to ensure adequate calcium supplementation while avoiding the risks associated with injudicious use.
Introduction:Polycystic ovarian syndrome (PCOS) predisposes females to metabolic syndrome, diabetes mellitus, and cardiovascular diseases. Continuous glucose monitoring system (CGMS) offers the advantage of better understanding of glycaemic variability as compared to oral glucose tolerance test (OGTT). There is scarce data regarding use of CGMS in understanding glycaemic variability in patients of PCOS. Methods:Fifty nondiabetic PCOS patients of age group 16-45 years diagnosed by Rotterdam criteria (2003) were included and subjected to CGM for 72 hours. Results:The mean age of participants was 23.32 ± 4.58 years. Family history of diabetes mellitus in a first degree relative was present in 40% patients. On OGTT, dysglycemia was present in 14 patients-5 (10%) had impaired fasting glucose (IFG), 6 (12%) had impaired glucose tolerance (IGT), and 6 (12%) had both IFG and IGT. Glycemic variability and post prandial glycaemic excursion (PPGE) were found to have significant positive correlation with Luteinizing hormone: Follicle-stimulating hormone (LH: FSH) ratio [r = 0.37 (P = 0.008) and r = 0.39 (P = 0.004)], respectively. Fasting and 2-hour OGTT plasma glucose, serum testosterone, mean blood glucose (MBG), eA1c, total PPGE, and PPGE for breakfast values were significantly higher in patients having homeostatic model assessment insulin resistance (IR) >2.5. MBG, eA1c, and PPGE for lunch and dinner were significantly high in patients with family history (FH) of diabetes mellitus (DM). There was no significant difference in CGM metrics among patients with or without hyperandrogenism (HA). Conclusion:CGMS detected high glycaemic variability and exaggerated post meal glycaemic excursions in Indian non diabetic PCOS patients having either positive family history of diabetes mellitus or IR or higher LH: FSH ratio.
Introduction:Subclinical hypothyroidism is defined as a serum thyroid-stimulating hormone (TSH) level above the upper limit of normal despite normal levels of serum free thyroid hormones. While the cardiovascular risk in overt hypothyroidism is well established, the risk in subclinical hypothyroidism, especially those with TSH <10 uIU/ml, is not clear. Here, we aimed to study the cardiovascular risk among subclinical hypothyroid individuals with TSH <10 uIU/ml by using epicardial fat thickness (EFT) measurement. Methods:This was a cross-sectional study conducted over 19 months. In this study, we included 35 cases of subclinical hypothyroidism who had a TSH <10 uIU/ml and 35 age- and sex-matched controls. A single expert cardiologist did EFT assessment for all the cases and controls. Results:The median (25th-75th percentile) EFT was significantly higher in cases (3.8 [2.85-4.775] mm) compared to controls (2.6 [2-3.55]mm, P = 0.0002). A significant, moderately positive correlation was seen between TSH and EFT, with a correlation coefficient of 0.561. Subgroup analysis showed that the median EFT was significantly higher in the ≥7.6 to <10 uIU/ml TSH group (4.4 [3.825-5] mm) compared to the >5.33 to <7.6 uIU/ml group (2.8 [2.2-3.5] mm, P = 0.002). LDL and TSH were associated with high EFT (>4 mm). The receiver operating characteristic curve analysis showed that the discriminatory power of TSH (AUC 0.741; 95% confidence interval [CI]: 0.577 to 0.906) and LDL (AUC 0.752; 95% CI: 0.580 to 0.924) were acceptable to predict EFT >4 mm. Conclusion:Individuals with SCH exhibited significantly higher EFT compared to euthyroid controls, with a positive correlation observed between TSH levels and EFT.
Thyroid dysfunction (TD) and cardiovascular disease (CVD) commonly coexist in older adults, where age-related vascular, mitochondrial, and autonomic changes heighten sensitivity to even mild hormonal imbalance. Thyroid hormones (THs) regulate cardiac and vascular function through genomic and non-genomic pathways, but aging alters receptor sensitivity, deiodinase (DIO) activity, and epigenetic control, resulting in tissue-specific TH insufficiency despite normal serum levels. Subclinical hypothyroidism (SCH) and low-T3 syndrome are especially prevalent in older adults and are linked to higher risks of heart failure (HF), atherosclerosis, atrial fibrillation, and mortality. Emerging data underscore the role of epigenetic regulators and the gut-thyroid-heart axis in modulating CV responses to TH imbalance. Clinically, routine thyroid function assessment is crucial in CVD, with management tailored to age-related risks. Tissue-selective TH based therapies represent a promising frontier for precision cardioprotection.
Introduction: Despite initiatives, the lack of understanding and improper usage habits for iodized salt are still prevalent. This cross-sectional study was conducted in rural Thiruvallur district of Tamil Nadu to assess the amount of iodine in the salt consumed, determine dietary iodine consumption, urinary iodine concentration, and understand the knowledge and practices related to iodized salt usage. Methods: A questionnaire was designed and validated to assess knowledge and practices of procuring, storing salt, and cooking practices. A standard field-testing kit was used to estimate the salt’s iodine level, and World Health Organization (WHO) guidelines values were taken for adequacy of iodization. Per capita consumption of salt was calculated by dividing the monthly purchase by family members partaking and iodine intake was calculated from a three-day dietary recall using the US FDA database. Spot urinary samples were collected to estimate the Median Urinary Iodine Concentration (MUIC). Results: Out of 650 households, 79% procured packaged salt; 40% were not aware of iodized salt; and 50.4% felt that consuming iodized salt is not important. The majority (91%) of the subjects added iodized salt at the beginning of cooking, 95% covered the storage container, and 32% exposed the salt to heat. Around 31% used uniodized or inadequately iodized salt. More than a quarter (27%) of them had the MUIC in the deficient range. Conclusion: A third of the population continues to use inadequately iodized salt, and the awareness of IDD and the importance of iodized salt is low.
Introduction: Testosterone (T) is commonly administered intramuscularly to treat hypogonadal males and female-to-male (FTM) transgender patients. Intramuscular testosterone administration has various drawbacks, including discomfort, bruising, pain, and the need to be administered by a healthcare professional. Self-administered subcutaneous route may be a convenient, safe, and effective alternative. The current study assesses the efficacy and safety of low-dose (50 mg) weekly subcutaneous testosterone administration among FTM transgender. Methods: The current retrospective cohort study included adult FTM transgender subjects. Participants were administered T-cypionate weekly at a dose of 50 mg and followed up for 6 months. At the end of the follow-up, serum concentrations of testosterone, oestradiol (E2), and the number of participants achieving target E2 (<50 pg/mL) and testosterone (300–700 ng/mL) levels were determined. Results: The patient cohort consisted of 22 FTM transgender subjects. The average age was 29 years and body mass index was 26.3 ± 3.3 kg/m2. After 6 months of follow-up, a significant rise in testosterone to 511.3 ± 204.3 ng/mL (P < 0.0001) and a significant decrease in E2 levels to 46.6 ± 16.2 (P < 0.0001) were noted in study subjects compared to baseline. Target testosterone and E2 levels were achieved (>300 ng/mL) in 81% and 68% of subjects, respectively. Ninety-one per cent of subjects had cessation of menstruation. No subject needed to stop testosterone injections or decrease dosage due to polycythaemia (PCV > 50%). Conclusion: Weekly self-administered 50 mg low-dose, subcutaneous testosterone injection was effective in achieving target testosterone and oestradiol levels in FTM transgender subjects, without significant safety issues.
Antipsychotic medication-induced weight gain (AIWG) is a difficult-to-manage condition. Semaglutide is a widely used weight-lowering agent, but its role in AIWG has been evaluated in only few studies. This SRM evaluated if semaglutide can be effectively and safely used for AIWG in schizophrenia, bipolar disorder, and other psychiatric diseases. Electronic databases were searched for articles evaluating the use of semaglutide for managing AIWG. The primary outcome was reduction in body weight. Secondary outcomes were changes in body mass index (BMI), waist circumference (WC), HBA1c, metabolic parameters, and adverse events. Data from nine studies (44,233 participants; 4.21% diabetes; 94.79% euglycemia) which fulfilled all criteria were analysed. Semaglutide for AIWG was associated with a significant reduction in weight [mean difference (MD) -7.37 kg (95% confidence interval (CI): -12.39, -2.35); P < 0.001; I2 = 99%], BMI [MD -2.76 kg/m2 (95% CI: -4.15, -1.37); P < 0.001; I2 = 98%], WC [MD -5.12 cm (95% CI: -7.21, -3.03); P < 0.001; I2 = 76%], HbA1c [MD -0.35% (95% CI: -0.47, -0.24); P < 0.001; I2 = 91%] and higher >5% weight loss [OR 2.25 (95% CI: 2.14, 2.36); P < 0.001; I2 = 0%]. The occurrence of nausea, diarrhoea, and injection site reactions was similar. Vomiting was significantly higher in semaglutide users. The occurrence of psychiatric adverse events was lower in semaglutide users but not significant [OR 0.59 (95% CI: 0.33–1.07); P = 0.08; I2 = 0%]. Semaglutide has good efficacy data with regard to quantum of weight loss with good safety for managing AIWG.
Introduction: Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment but are associated with agent-specific spectra of endocrine-related adverse events (irAEs). Data on prevalence of ICI-induced endocrinopathies in Indian populations remain limited. A study was conducted with an aim to determine the prevalence and spectrum of endocrinopathies resulting from ICI therapy in cancer patients at a tertiary care centre. Methods: This prospective cohort study included 100 adult cancer patients initiated on ICI therapy (anti-PD1 or PD-L1). Patients with pre-existing endocrinopathies or those diagnosed during baseline assessment were excluded. Comprehensive clinical, biochemical, and hormonal assessments were performed at baseline and during follow-up at 1, 2, 3, 6, 9, and 12 months. Endocrinopathies were diagnosed per standard criteria. Associations with demographic and clinical variables were analysed using Fisher’s exact test. Results: Endocrinopathies developed in 19% of participants during 12 months of follow-up. Primary hypothyroidism was most frequent (12%), followed by hypergonadotropic hypogonadism (3%), diabetes mellitus (2%), primary adrenal insufficiency (1%), and primary hyperparathyroidism (1%). The median age of those affected was 52.6 years, with a male predominance. Endocrinopathies occurred more commonly with PD-1 inhibitors compared to PD-L1 inhibitors. Hypertension was significantly associated with endocrinopathy development (P = 0.044). Most endocrinopathies presented within the first six months of ICI therapy. Conclusion: ICI-induced endocrinopathies are prevalent among Indian cancer patients, with primary hypothyroidism being the most common. Early onset irAEs underscore the need for regular endocrine monitoring during and after ICI therapy.
Introduction: Bisphosphonates (BP) used in osteoporosis management can induce an acute phase response, their short-term endocrine effects remain unclear. This study hypothesized that initial BP exposure elicits a non-thyroidal illness syndrome (NTIS)-like pattern and that thyroid autoimmunity may amplify this response. Methods: In this prospective cohort at a tertiary centre, 336 adults (93% postmenopausal women) were enrolled: 168 received first-dose BP therapy (zoledronic acid (ZA) =129; oral alendronate (ALN) = 39) and 168 matched controls (calcium/vitamin D). FT3, FT4, TSH, and erythrocyte sedimentation rate (ESR) were measured at baseline and on days 1, 2, 3, 7, and 42 with baseline anti-TPO Ab. Linear mixed-effects models with random intercepts evaluated group × time interactions, adjusting for age, sex, and body mass index. Results: BP recipients demonstrated a clear temporal pattern, FT3 declined significantly, reaching a nadir on Day 2 (mean difference −0.47 pg/mL vs controls, P < 0.001), FT4 fell modestly (mean difference −0.07 ng/dL), and TSH was transiently suppressed before rebounding above baseline by Day 42 (mean difference +0.39 mIU/L). ESR peaked on Day 2 and normalized by Day 7, paralleling hormonal recovery. Group × time interactions were significant for all parameters (P < 0.05). Anti-TPO Ab positive individuals exhibited deeper FT3 suppression and greater TSH rebound. ALN effects were directionally similar but underpowered. Conclusion: First-dose BP therapy, particularly ZA, induces a short-lived, reversible NTIS-like response amplified by thyroid autoimmunity. Early post-infusion thyroid testing may mimic hypothyroidism, re-evaluation after six to eight weeks is recommended.
Introduction: The role of dipeptidyl peptidase-4 (DPP-4/CD26) in chronic liver disease (CLD) remains incompletely understood, particularly its interaction with immune cells. This study investigates the association between DPP-4 gene expression and T-cell subset marker genes in CLD patients, aiming to elucidate potential immunological mechanisms underlying disease progression. Methods: A total of 130 individuals were enrolled across four groups: non-alcoholic fatty liver disease (NAFLD; n = 46), non-alcoholic cirrhosis (NAC; n = 23), alcoholic cirrhosis (ALC; n = 21), and healthy controls (n = 40). Peripheral blood samples were analysed for biochemical parameters and DPP-4 activity. Gene expression profiling was conducted in peripheral blood mononuclear cells to assess DPP-4 and T-cell marker genes (TBX21, RORC, GATA3, FOXP3, and CD3D). Results: DPP-4 expression was elevated in all CLD subgroups, reaching statistical significance in NAFLD (P = 0.0142). The Th1 marker TBX21 showed increased expression, significantly in NAC (P = 0.0091), and demonstrated a strong correlation with DPP-4 in non-alcoholic CLD. The Th17 marker RORC was significantly elevated in NAFLD (P = 0.016), whereas the Th2 marker GATA3 and the Treg marker FOXP3 were significantly reduced (P = 0.0049 and P = 0.0028, respectively), with FOXP3 showing a negative correlation with DPP-4 (r = 0.588). CD3D expression correlated with DPP-4 in ALC patients. Conclusion: These findings suggest disrupted regulatory coordination rather than uniform Treg suppression across CLD subgroups. NAFLD exhibited partial Th17 polarisation, whereas NAC may reflect Th17 exhaustion. DPP-4 appears to be associated with Th1 responses and may contribute to liver injury in NAC.
Introduction: Obesity and type 2 diabetes (T2D) are rapidly increasing in India. Although newer glucagon-like peptide/glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists have demonstrated considerable efficacy in weight loss, real-world evidence from the Indian population is lacking. This study evaluated the response to semaglutide and tirzepatide in overweight/obese individuals in routine clinical practice. Methods: This retrospective cohort study was conducted at a tertiary centre in New Delhi, India. Data from 150 overweight/obese participants (74 with T2D, 76 without T2D) treated with semaglutide/tirzepatide over 6 months were analysed. Outcomes included percentage weight loss, achievement of predefined weight-loss thresholds, time-to-event (≥10% weight loss), and determinants of time-to-event. Non-parametric tests and Cox proportional hazard regression were used for analysis. Results: The median weight loss was 8.2% (4.93–13.66). Participants without T2D achieved significantly greater weight loss than those with T2D (11.21% vs 5.48%, P < 0.001). Tirzepatide was associated with greater weight loss compared with semaglutide (8.60% vs 5.62%, P = 0.023). Sixty-two participants (41.3%) achieved a weight loss of ≥10%, with a median time-to-event of 9.5 months. Multivariable analysis identified younger age, tirzepatide use, and GLP1 treatment naivety as determinants of faster achievement of ≥10% weight loss. Diabetes status was not associated with faster achievement of ≥10% weight loss. Conclusion: In this real-world Indian cohort, GLP-1/GIP receptor agonists were effective means for weight loss in obese adults, with or without T2D. The magnitude and speed of weight loss outcomes may help in personalising therapy and setting expectations when initiating newer GLP-1/GIP receptor agonists.
