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Asian-Indians show thin fat phenotype, characterized by predominantly central deposition of excess fat. The roles of abdominal subcutaneous fat (SAT), intra-peritoneal adipose tissue, and fat depots surrounding the vital organs (IPAT-SV) and liver fat in insulin resistance (IR), type-2 diabetes (T2D) and metabolic syndrome (MetS) in this population are sparsely investigated. Assessment of liver fat, SAT and IPAT-SV by MRI in subjects with T2D and MetS; and to investigate its correlation with IR, specifically according to different quartiles of HOMA-IR. Eighty T2D and the equal number of age sex-matched normal glucose tolerant controls participated in this study. Abdominal SAT, IPAT-SV and liver fat were measured using MRI. IR was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). T2D and MetS subjects have higher quantity liver fat and IPAT-SV fat than controls (P = 9 x 10-4 and 4 x 10-4 for T2D and 10-4 and 9 x 10-3 for MetS subjects respectively). MetS subjects also have higher SAT fat mass (P = 0.012), but not the BMI adjusted SAT fat mass (P = 0.48). Higher quartiles of HOMA-IR were associated with higher BMI, W:H ratio, waist circumference, and higher liver fat mass (ANOVA Test P = 0.020, 0.030, 2 x 10-6 and 3 x 10-3 respectively with F-values 3.35, 3.04, 8.82, 4.47 respectively). In T2D and MetS subjects, HOMA-IR showed a moderately strong correlation with liver fat (r = 0.467, P < 3 x 10-5 and r = 0.493, P < 10-7), but not with SAT fat and IPAT-SV. However, in MetS subjects IPAT-SV fat mass showed borderline correlation with IR (r = 0.241, P < 0.05), but not with the BMI adjusted IPAT-SV fat mass (r = 0.13, P = 0.26). In non-T2D and non-MetS subjects, no such correlation was seen. On analyzing the correlation between the three abdominal adipose compartment fat masses and IR according to its severity, the correlation with liver fat mass becomes stronger with increasing quartiles of HOMA-IR, and the strongest correlation is seen in the highest quartile (r = 0.59, P < 10-3). On the other hand, SAT fat mass tended to show an inverse relation with IR with borderline negative correlation in the highest quartile (r = -0.284, P < 0.05). IPAT-SV fat mass did not show any statistically significant correlation with HOMA-IR, but in the highest quartile it showed borderline, but statistically insignificant positive correlation (P = 0.07). In individuals suffering from T2D and MetS, IR shows a trend towards positive and borderline negative correlation with liver fat and SAT fat masses respectively. The positive trend with liver fat tends to become stronger with increasing quartile of IR. Therefore, these findings support the theory that possibly exhaustion of protective compartment's capacity to store excess fat results in its pathological deposition in liver as ectopic fat.

The roles of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) in the molecular pathogenesis type-2 diabetics (T2D) among Asian Indians showing a “thin fat” phenotype largely remains obscure. In this study, we generated transcription profiles in biopsies of these adipose depots obtained during surgery in 19 diabetics (M: F ratio, 8:11) and 16 (M: F ratio 5:11) age- and BMI-matched non-diabetics. Gene set enrichment analysis (GSEA) was used for comparing transcription profile and showed that 19 gene sets, enriching inflammation and immune system-related pathways, were upregulated in diabetics with F.D.R. <25% and >25%, respectively, in VAT and SAT. Moreover, 13 out of the 19 significantly enriched pathways in VAT were among the top 20 pathways in SAT. On comparison of VAT vs. SAT among diabetics, none of the gene sets were found significant at F.D.R. <25%. The Weighted Gene Correlation Analysis (WGCNA) analysis of the correlation between measures of average gene expression and overall connectivity between VAT and SAT was significantly positive. Several modules of co-expressed genes in both the depots showed a bidirectional correlation with various diabetes-related intermediate phenotypic traits. They enriched several diabetes pathogenicity marker pathways, such as inflammation, adipogenesis, etc. It is concluded that, in Asian Indians, diabetes pathology inflicts similar molecular alternations in VAT and SAT, which are more intense in the former. Both adipose depots possibly play a role in the pathophysiology of T2D, and whether it is protective or pathogenic also depends on the nature of modules of co-expressed genes contained in them.

Background and Objectives: Differentiation of growth hormone deficiency (GHD) into various types has been made based on peak stimulated growth hormone levels and other hormone axis involvement. The data regarding how this classification is associated with variation in clinical and biochemical phenotype and how these findings associate with pituitary morphology remains sparse, especially in the Indian population. Therefore, we aimed to ascertain the differences in the pattern of auxological, clinical features including pituitary hypoplasia, and endocrinological profile among patients with severe GHD, partial GHD, and MPHD in the Indian population and to evaluate the association of pituitary height with various clinical and hormonal parameters. Materials and Methods: We conducted a cross-sectional study in 100 patients with idiopathic GHD. Patients were grouped into severe GHD, partial GHD, and MPHD to observe the differences in clinical, biochemical, and MRI findings. The pituitary height findings were correlated clinical and biochemical presentation. Results: MPHD subjects had a significantly higher frequency of breech delivery, neonatal jaundice, neonatal hypoglycemia, and micropenis. A significant difference was observed in the chronological age, bone age retardation (CA-BA), height SDS, weight SDS, peak GH response, IGF-1, IGF-1 SDS, and prevalence of pituitary hypoplasia, pituitary height, and pituitary height SDS among these three groups. In the composite population of GHD, pituitary height SDS was correlated with peak GH, basal IGF-I SDS, and body height SDS. Conclusion: The clinical and biochemical phenotype differs significantly among the various types of GHD. Pituitary height correlates with these findings and is helpful in further assessment of these patients.

Objective: Efficacy of bilateral inferior petrosal sinus sampling (BIPSS) in corticotropin-dependent Cushing's syndrome (CS) for localization and lateralization of excess adrenocorticotropic hormone (ACTH) source, as compared to high-dose dexamethasone suppression test (HDDST) and magnetic resonance imaging (MRI) pituitary, respectively. Methodology: Thirteen patients with clinically and biochemically confirmed CS underwent HDDST, MRI pituitary, and BIPSS by an experienced team of intervention neurologist, neurosurgeon, and endocrinologist using percutaneous femoral vein approach. Results: Of 13 patients (11 adults and two children) who underwent BIPSS, raised central to peripheral ACTH ratio was achieved in 12 cases, remaining one case being ectopic ACTH secretion (EAS). However, inter IPS gradient >1.4 was achieved in 11 (91.6%) of 12 Cushing's disease (CD) cases before vasopressin stimulation; and in 9 (75%) of 12 CD cases after vasopressin stimulation (P-value 0.583). HDDST suppression of more than 50% was present in only ten cases with CD, falsely negating CD in two cases (16.6%), sensitivity 83.3% and specificity 100%. MRI sella demonstrated pituitary microadenoma in 12 cases and macroadenoma in one case. Lateralization by BIPSS and MRI was concordant in 7 (58.3%) out of 12 cases with CD, with rate of remission after transsphenoidal surgery being higher in patients with concordant lateralization by BIPSS and MRI. Conclusions: BIPSS is an important investigation to distinguish CD and EAS. BIPSS was superior to HDDST for confirming the source of excess ACTH. Our findings favor the use of BIPSS for localization and pituitary MRI for lateralization of microadenoma.

Type 2 diabetes mellitus (T2DM) may affect bone loss differentially in adult males and postmenopausal females. We evaluated the prevalence of osteoporosis in otherwise healthy adults with T2DM. In a cross-sectional study, adults with T2DM, aged 50 years and above, were evaluated for bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) scan at spine and hip. T-score of ≤-2.5 was defined as osteoporosis and score -2.49 to -1.0 as osteopenia at either site. Correlation of low BMD with demographic, clinical, and laboratory parameters including serum Vitamin D and serum testosterone (in males) was evaluated. In 200 patients, mean age was 64.5 ± 7.0 years and age differed significantly in males and females ( < 0.0001). Osteoporosis was present in 35.5% adults with T2DM. Significantly greater proportion of females had osteoporosis (49.5% vs. 22.3%, < 0.0001). Frequency of osteoporosis at spine (33.5%) was higher than the same at hip (13.5%). Compared to males, significantly greater proportion of females had osteoporosis and osteopenia at both spine ( < 0.0001) and hip ( < 0.0001). Among all parameters assessed, a significant positive correlation of T-score at spine and hip was seen with body mass index in both males ( = 0.287, = 0.003 at spine and = 0.421, < 0.0001 at hip) and females ( = 0.291, = 0.004 at spine and = 0.280, = 0.010 at hip). There was no association of Vitamin D deficiency (45.5% patients) with either T-score and presence of osteoporosis either at spine ( = 0.388 and = 0.177) or hip ( = 0.431 and = 0.593). Prevalence of osteoporosis in otherwise healthy T2DM was 35.5% with greater prevalence in females than males. Body mass but not Vitamin D or testosterone has an important role in the determination of bone loss in T2DM.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Introduction: Type 1 diabetes mellitus (T1DM) is associated with various autoimmune disorders like celiac disease, thyroid disorder, adrenal failure, etc. However, how common is this association in Indian children is not clearly known. Objective: To assess the prevalence of other coexisting autoimmune disorders in children with T1DM. Materials and Methods: In this cross-sectional study, patients requiring insulin and ketosis-prone diabetic and with history of diabetic ketoacidosis/undetectable fasting C-peptide levels were included. Beside demographic and clinical data, detailed biochemistry evaluations were performed. Celiac disease was diagnosed as per the ESPGHAN diagnostic criteria. ACTH stimulation test was done to confirm the adrenal insufficiency in patients with basal serum cortisol <5 μg/dL. Thyroid function test (TSH) and anti-TPO antibody were assessed in all patients. Screening for other autoimmune disorders was done only when clinically indicated or symptoms or family history was suggestive of presence of such disorder. Results: Among 150 patients enrolled, 64.66% were males and mean age was 13.48 ± 3.29 years (range 3-18 years). Mean age at diagnosis of T1DM was 10.0 ± 3.63 years and duration of diabetes was 3.46 ± 3.18 years. The prevalence of antibodies positive against autoimmune diseases was anti-tTG IgA (20.7%), anti-TPO (33.7%), anti-CCP ab (1.3%), and ANA (0.7%). Significantly higher proportion of females had raised anti-TPO antibodies than males (47.2% vs. 25.8%, P = 0.006). Celiac disease was most common association (24.8%) followed by hypothyroidism (14.1%) and Grave's disease (3.3%). Significantly higher proportion of females had hypothyroidism than males (25.0% vs. 8.2%, respectively, P = 0.005). Prevalence of raised anti-tTG and anti-TPO did not differ significantly by the age (P = 0.841 and P = 0.067) or duration of T1DM (P = 0.493 and P = 0.399). Conclusion: In this part of country, celiac disease, hypothyroidism, and Graves's disease are common associations in children with T1DM.

Objectives: Idiopathic hypogonadotropic hypogonadism (IHH) can be associated with anosmia/hyposmia. The objective of this study is to evaluate olfaction by Indian smell identification test (INSIT) and measure olfactory bulbs (OBs) and sulci using dedicated magnetic resonance imaging (MRI) in patients with IHH and correlate MRI findings with INSIT. Methods: Forty patients with IHH underwent (a) brief smell identification test (INSIT) and (b) MRI of the olfactory apparatus. The size of olfactory sulcus and bulb was quantified and compared with the normative data obtained in 22 controls. The agreement between INSIT and MRI was assessed using Kappa index. Results: Of the 40 patients, 8 patients who reported abnormal smell sensation and 12 of the remaining 32 patients who reported normal smell sensation historically had a low score on INSIT. Thus, there were 20 patients with Kallmann syndrome (KS) and the rest 20 were normosmic IHH (nIHH). Of 40 patients with IHH, MRI finding was suggestive of normal (n = 16), hypoplastic (n = 12), and aplastic (n = 12) olfactory apparatus. All 20 patients with KS have olfactory abnormalities (n = 12 aplastic, n = 8 hypoplastic), and 4 of 20 nIHH have olfactory abnormalities (hypoplastic only) on MRI. There is (a) significant positive correlation (r = 0.54, P = 0.013) between the OB volume (MRI) and smell test scores and (b) moderate agreement (Kappa index: 0.49) between smell defect (INSIT score ≤ 4) and aplastic olfactory apparatus. Conclusion: Self-reporting of smell significantly underestimates olfactory phenotype, and hence we recommend an objective smell test to differentiate KS from nIHH. Olfactory phenotype significantly correlates with MRI quantification of olfactory apparatus in IHH.

Abstract Disclosure: K. Gupta: None. B. Sharma: None. S. Saran: None. S.K. Mathur: None. Predicting Growth hormone (GH) therapy response remains challenging in diverse real-world pediatric populations. While the Ranke formula is widely used, its generalizability and accuracy in Indian children remain untested. This prospective observational study included 45 GH-naïve children with GHD from a tertiary Indian center. Baseline and 12-month data included height SDS, growth velocity, bone age, IGF-1, weight SDS, pituitary volume (MRI), and GH dose. The primary outcome was growth velocity (≥10 cm/year); Δ height SDS (>0.5) was evaluated as a secondary outcome. Three predictive models were compared using AUC and RMSE. GH dose-response simulations evaluated individualized dosing potential. The results showed a mean height SDS improvement from –3.15 ± 0.98 to –2.28 ± 0.89 (Δ 0.87 ± 0.35). The mean growth velocity was 10.4 ± 1.9 cm/year. Good response (≥10 cm/year) was observed in 89% children. IGF-1 SDS and bone age delay were significantly associated with height gain (p < 0.01). Younger age and higher GH dose were also predictive of a better response (p < 0.05). Pituitary volume was not independently predictive. Model comparisons showed Random Forest: AUC = 0.84, RMSE = 0.35 SDS (1.78 cm/year); Linear Regression: AUC = 0.74, RMSE = 0.43 SDS (2.21 cm/year); Ranke Formula: AUC = 0.72, RMSE = 0.46 SDS (2.41 cm/year). Dose simulations showed minimal benefit from escalation suggesting standard GH doses were adequate in most cases.This is the first prospective Indian study comparing ML, traditional regression and published formula-based models in GHD. ML outperformed other models in predicting GH response. IGF-1 SDS, bone age delay, and GH dose emerged as key predictors. These findings support the use of AI based tools trained on local data for early prognostication and personalization of GH therapy in children with GHD. Presentation: Saturday, July 12, 2025