Endocrine Connections最新文献

Background: Obesity and type 2 diabetes mellitus (T2DM) are burgeoning public health challenges. Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) have gained prominence because they improve glycemic control and aid weight reduction by slowing gastric emptying and promoting satiety. Liraglutide is a once-daily human GLP-1 analogue marketed for T2DM (at 1.8 mg) and weight management (3.0 mg), whereas semaglutide is a more potent GLP-1 RA administered once weekly at doses of 1.0 mg (diabetes) and 2.4 mg (weight management). Randomized controlled trials suggest that semaglutide yields greater weight loss and HbA1c reduction than liraglutide [1, 2], yet comparative data in real-world South Asian populations are limited.

Methods: We performed a prospective, open-label, randomized study at Lady Reading Hospital, Peshawar, Pakistan. Adults with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) with T2DM were randomized (1:1) to once-weekly semaglutide 2.4 mg plus lifestyle counselling or once-daily liraglutide 3.0 mg plus the same counselling. The primary outcome was the percentage change in body weight at 68 weeks. Secondary outcomes included proportions achieving weight-loss thresholds (≥ 5%, ≥ 10 % and ≥ 15 %) [3]; change in HbA1c [4], fasting glucose, waist circumference, blood pressure, lipid profile, patient-reported quality of life, and adverse events. Mean changes were compared using t-tests; categorical outcomes were compared using χ2 tests.

Results: Two hundred forty participants (mean age 45.6 ± 9.8 years, 52 % women) were enrolled. At 68 weeks, semaglutide recipients lost significantly more weight than liraglutide recipients (-14.7 ± 5.8 % vs -6.2 ± 4.9 %; p < 0.001), consistent with STEP 8 trial findings [1]. A greater proportion of semaglutide patients achieved ≥ 10 % and ≥ 15 % weight loss (70.9 % and 55 %) compared with liraglutide (25.6 % and 12 %) [3]. HbA1c decreased by -1.6 ± 0.4 % with semaglutide versus -1.0 ± 0.4 % with liraglutide (p < 0.001), mirroring SUSTAIN-10 differences [5]. Gastrointestinal adverse events were common but similar between groups (83.5 % vs 82.0 %); nausea and vomiting occurred more frequently with semaglutide [6].

Conclusions: In a real-world Pakistani cohort, once-weekly semaglutide produced substantially greater weight loss and HbA1c reduction than daily liraglutide, with comparable tolerability. These findings support the preferential use of semaglutide for weight management and glycemic control, particularly when once-weekly dosing improves adherence. Further studies should explore long-term sustainability, cardiovascular benefits, cost-effectiveness, and optimal integration with lifestyle interventions.

Background/objectives: Glucose-dependent insulinotropic polypeptide (GIP) is secreted by enteroendocrine K cells in response to nutrient ingestion. The aims of this study were: i) to evaluate the cross-sectional associations between plasma GIP change in response to an oral glucose challenge (as a surrogate of GIP secretion) with obesity-related anthropometric measurements, fasting inflammatory biomarkers, and fasting circulating adipokines; and ii) to evaluate the feasibility of using postprandial plasma GIP as a biomarker of adiposity-related phenotypes in response to starch-based meals.

Methods: Fifty normoglycemic women without obesity (19-32 years) were evaluated with an oral glucose tolerance test (OGTT). A feasibility study was conducted in a subset of eight women to estimate responses to starch-based meals (25 g of starch). Postprandial glycemic-related changes in plasma hormones/metabolites were assessed, and circulating adipokines and inflammatory biomarkers in fasting conditions.

Results: The incremental-GIP change after 2 h OGTT was significantly associated with waist circumference (rho = 0.34; P = 0.02), fasting plasma TNF-α (rho = 0.54; P = 0.0002), and white blood cell count (rho = 0.39; P = 0.008), but not with MCP-1, total adiponectin, leptin, or the free leptin index. A strong inverse association was found between incremental-GIP change and fasting plasma high-molecular-weight (HMW) adiponectin (rho = -0.50; P = 0.0004), which remained significant after adjusting for age and body mass index.

Conclusion: An inverse association was found between postprandial GIP levels and circulating HMW-adiponectin levels in humans. This work highlights the suitability of using postprandial plasma GIP as a biomarker for metabolic disturbances of increased adiposity, even in the absence of obesity.

Introduction: Most phaeochromocytomas produce insulin, and some produce glucagon-like peptide 1 receptor (GLP-1R). In pancreatic β-cells, stimulation of GLP-1R causes insulin release. A few phaeochromocytoma patients experience hypoglycaemic attacks. Therefore, we studied the distribution of GLP-1R-containing and insulin-containing phaeochromocytoma cells and their relation.

Methods: In 20 phaeochromocytomas, we performed sequential double staining with anti-insulin and anti-GLP-1R antibodies and, in selected cases, staining with anti-insulin alone. We quantified tumour cells with positive staining and compared their distribution to that of randomly distributed cells using simulations. We obtained GLP-1R transcript data from 182 such tumours from The Cancer Genome Atlas (TCGA) Research Network.

Results: GLP-1R-containing cells were found in six of the 20 tumours, and insulin-containing cells were found in fifteen. Moreover, in the TCGA cohort, almost half of the tumours produce GLP-1R transcripts, and patients with the highest number of transcripts show longer disease-free survival. In the tumours, we found that cells expressing insulin were present in the cytoplasm and GLP-1R in the membrane, with a frequency of 2.59 and 1.34%, respectively. These cells showed clustering, and one tumour showed a large clonal expansion. Interestingly, we found deposits of insulin, which we suggest naming insulin bodies in two tumours. Very few cells contained both proteins.

Conclusion: Most phaeochromocytomas contain tumour cells producing insulin. About half produce GLP-1R. The producing cells show clustering, and clonal expansion occurs. Insulin release might cause hypoglycaemia. Increased GLP-1R levels might induce less aggressive tumours.

Objective: Strain imaging serves as a sensitive marker for detecting early subclinical myocardial systolic dysfunction. The purpose of this study was to evaluate the diagnostic and prognostic value of myocardial work indices in assessing subclinical myocardial systolic dysfunction in active acromegaly patients.

Methods: 27 active acromegaly patients and 27 healthy controls matched for age, sex, height, weight, body mass index and body surface area were included in the study. Active acromegaly was diagnosed based on elevated serum insulin-like growth factor 1 (IGF-1) (>1× upper limit of normal) or insufficient GH suppression (nadir ≥0.4 ng/mL) during an OGTT. All participants underwent two-dimensional speckle-tracking echocardiography (2D-STE) for the assessment of cardiac function. STE extracted the corresponding strain parameters (such as global longitudinal strain (GLS), global circumferential strain and global radial strain) and work parameters (such as global work index, global constructive work, global wasted work (GWW) and global work efficiency (GWE)) by analyzing the motion (strain)-velocity (strain rate) of two or more local myocardial segments, combined with the left ventricular non-invasive pressure estimation technique. At the same time, correlation analysis was used to explore the factors affecting GWW and GWE in the acromegaly group.

Results: In comparison with the control group, conventional echocardiography revealed that acromegaly patients did not exhibit a significant difference in left ventricular ejection fraction (60.3 ± 3.7 vs 59.1 ± 4.8, P = 0.312), a commonly used index to evaluate ventricular systolic function, STE showed that there was no significant difference in GLS (-18.3 ± 2.4 vs -17.4 ± 2.9, P = 0.514) between the control group and the acromegaly group. However, significant differences can be found in GWW (44.8 ± 31.1 vs 80.6 ± 75.6, P = 0.027) and GWE (97.0 ± 1.8 vs 95.0 ± 3.8, P = 0.020), and a significant correlation was observed between myocardial work parameters and 1.5 × ULN IGF-1.

Conclusion: GWW and GWE are sensitive markers for identifying subclinical myocardial systolic dysfunction, suggesting their potential as early markers for detecting subclinical myocardial systolic dysfunction in active acromegaly patients.

Objective: Cystic fibrosis (CF) is a congenital condition caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF-related diabetes (CFRD) is a common comorbidity among people with CF (pwCF) and is associated with increased morbidity. Previous in vitro studies have suggested that CFTR dysfunction is involved in the pathogenesis of CFRD. This prospective study aimed to evaluate the role of CFTR in glucose homeostasis by comparing glucose, insulin, C-peptide, glucagon and GLP-1 responses during an oral glucose tolerance test (OGTT) in pwCF and healthy controls and in pwCF before and after initiating elexacaftor-tezacaftor-ivacaftor (ETI) therapy.

Methods: Twenty-four pwCF were enrolled, of which 18 underwent OGTT both before and after ETI initiation. Ten healthy controls were included for comparison. Plasma samples were collected at standard OGTT time points, including an additional 15 min sample. Hormonal and glucose responses during OGTT were compared across groups and in pwCF before and after starting ETI.

Results: Compared with healthy controls, pwCF exhibited impaired glucose regulation, delayed insulin secretion, decreased insulin sensitivity index and reduced disposition index, indicating beta-cell dysfunction. In addition, p-glucagon levels were elevated in pwCF. Following ETI therapy, pwCF showed improved glucose control, increased first-phase insulin secretion and normalized glucagon secretion.

Conclusions: These findings support a role for CFTR in islet hormone regulation, implicating direct effects on beta-cell function and a potential role in suppressing glucagon secretion.

Background: Metformin, the first-line treatment for type 2 diabetes, often induces gastrointestinal side effects, affecting treatment adherence. Recent research suggests that the gut microbiome mediates both the efficacy and tolerability of metformin. This study evaluates the effect of a polyherbal formulation, used as an add-on to metformin, on the gut microbiota in patients with type 2 diabetes and metformin intolerance.

Methods: We report preliminary findings from the first 7-day intervention phase of an ongoing randomized, placebo-controlled, crossover trial (NCT06846138) in 27 adults with type 2 diabetes. Participants received either polyherbal formulations or a placebo alongside metformin for 7 days. Stool samples were collected pre- and post-intervention for shotgun metagenomic sequencing. Microbial diversity, composition, and pathway functions were analyzed using Kraken2, Bracken, and HUMAnN3. Continuous glucose monitoring was used to assess glycemic metrics.

Results: No significant alpha-diversity changes were observed; however, beta-diversity differed significantly between arms (PERMANOVA R 2 = 0.04, P = 0.04). In the polyherbal formulation group, 17 species changed post-treatment (FDR < 0.25), with significant increases in six Bifidobacterium spp. (e.g., B. adolescentis, B. ruminantium). In contrast, the placebo group showed no major microbial shifts. Polyherbal formulation also altered ten microbial pathways (FDR < 0.25). Continuous glucose monitoring revealed no short-term changes in glycemic levels.

Conclusion: Short-term polyherbal formulation co-administration significantly modulates gut microbiota, promoting beneficial taxa, such as Bifidobacterium in metformin-treated type 2 diabetes patients. This supports the potential role of the polyherbal formulation in microbiome-targeted strategies to improve metformin tolerability and effectiveness.

Background: Graves' orbitopathy (GO) profoundly affects patients' quality of life, even in its mild form, yet the underlying factors contributing to this impairment remain underexplored. Recent evidence suggests the potential immune tolerance-inducing effect of immunoglobulin G4 (IgG4) in the pathogenesis of GO. However, its specific impact on quality of life and its significance in mild GO have not been well characterized.

Methods: This prospective multicenter study included patients with mild GO who were in euthyroidism. Quality of life was assessed using the validated GO-quality of life questionnaire (GO-QoL). Serum IgG4 levels and IgG4/IgG ratios were measured and analyzed in relation to GO-QoL scores and other clinical and biochemical parameters.

Results: Patients with mild GO exhibited significantly impaired quality of life, with the greatest impact seen in the appearance subscale. Notably, serum IgG4 levels were positively correlated with visual functioning scores in the GO-QoL (ρ = 0.248, P = 0.0466). Higher serum IgG4 levels were also associated with less limitation in driving and a longer duration of GO. Moreover, serum IgG4 levels and IgG4/IgG ratios showed significant positive correlations with male sex and clinical activity score.

Conclusions: This study highlights the significant impairment in the quality of life experienced by patients with mild GO and identifies serum IgG4 as a promising indicator for evaluating disease chronicity and quality of life, which may help guide different treatment strategies. Further prospective and basic studies are required to explore the role of IgG4 in the pathogenesis of GO.

Background: This study aimed to investigate the association between cerebrovascular disease (CBVD) and adverse in-hospital outcomes in patients with diabetic ketoacidosis (DKA).

Methods: We conducted a retrospective analysis using the National Inpatient Sample data from 2016 to 2022, identifying 445,863 hospitalizations among adults with diabetes and CBVD. Within this cohort, 4,363 patients had DKA and 1,648 had hyperosmolar hyperglycemic state (HHS). Multivariable logistic regression was employed to control for demographic, socioeconomic, admission, comorbidity, and hospital factors.

Results: Our findings revealed that among hospitalized adults with type 2 diabetes (T2DM) and CBVD, patients experiencing DKA had a significantly higher rate of in-hospital mortality compared to those with non-DKA/HHS cases. The likelihood of severe complications was notably increased in DKA patients. Furthermore, DKA hospitalizations were associated with an extended length of stay and an increased financial burden. When compared to HHS patients, those with DKA exhibited a greater risk of mortality, higher rate of complications, and higher resource utilization. In addition, within the cohort of patients with a primary diagnosis of T2DM DKA, those with CBVD had higher resource utilization and an increased incidence of complications.

Conclusions: Patients with DKA and CBVD experienced significantly poorer clinical outcomes and increased healthcare resource utilization compared to those with non-DKA/HHS and HHS. These findings highlight the adverse impact of CBVD on in-hospital outcomes for DKA patients, emphasizing the need for targeted prevention and timely multidisciplinary management strategies for this vulnerable population.

Objective: This study aimed to identify risk factors for osteoporosis (OP) in patients with primary aldosteronism (PA) and to develop a predictive nomogram for estimating OP risk in this population.

Methods: We retrospectively enrolled PA patients diagnosed at our hospital between January 2020 and December 2024. The dataset was randomly divided into training (n = 185) and validation (n = 79) sets in a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) regression combined with multivariate logistic regression was used to identify predictive factors for OP and construct the nomogram. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Additional performance assessments included the Hosmer-Lemeshow test, calibration curves, and decision curve analysis (DCA).

Results: The study included 264 PA patients (mean age 61.2 ± 10.0 years; 110 men, 154 women), with an OP prevalence of 11.4%. LASSO regression identified seven independent predictors: age, sex, body mass index, diabetes history, fasting insulin, plasma aldosterone concentration, and serum creatinine. The nomogram demonstrated strong predictive performance, with AUC values of 0.931 (95% CI: 0.879-0.982) in the training set and 0.842 (95% CI: 0.749-0.935) in the validation set. Calibration curves and DCA confirmed the model's clinical utility.

Conclusion: The developed nomogram effectively predicts OP risk in PA patients, offering valuable clinical utility for early identification of high-risk individuals.