Background: Epidermal Growth factor (EGF) plays a crucial role in cellular growth, differentiation, and pancreatic β-cell maintenance. Despite of reports in EGF deficiency in diabetic animal models, its relevance in type 2 diabetes (T2D), particularly in relation to obesity remains underexplored. The present study aimed to evaluate plasma EGF levels in individuals with and without T2D, assess its associations with glycaemic status and clinical parameters, and evaluate the influence of obesity on these relationships.
Methods: A total of 838 eligible participants were selected from the Kuwait Diabetes Epidemiology Program. Of those, 428 were included in a 1:1 case-control analysis (214 T2D and 214 non-diabetics). EGF was measured in plasma using ELISA. Associations between EGF with glycaemic and clinical variables were evaluated using Pearsons correlation, multiple linear and logistic regression analyses.
Results: Plasma EGF levels were significantly lower in individuals with T2D compared to non-diabetics (p<0.001). Among non-diabetics, obese participants had significantly lower EGF than their non-obese counterparts (p=0.03), while no such difference was observed in T2D. EGF negatively correlated with fasting blood glucose (FBG) in both non-diabetics (p=0.004) and T2D individuals (p<0.001). In T2D, EGF negatively correlated with haemoglobin A1C (HbA1C) (p=0.001), triglyceride (TG) (p=0.021), and waist to hip ratio (WHR) (p=0.014). Logistic regression confirmed that lower EGF levels were independently associated with T2D but not with general obesity (OR=0.996, p=0.001).
Conclusion: Reduced EGF levels are associated with poor glycaemic control in T2D. These findings highlight EGF's potential as a biomarker for glycaemic dysregulation and support further investigation into its role in diabetes pathophysiology and complications.
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Abstract: Hyperthyroidism adversely affects quality of life (QoL), encompassing physical, mental and social functioning and well-being. Patients with hyperthyroidism often complain of anxiety, physical symptoms and tiredness. Concurrent thyroid eye disease (TED) further reduces QoL. With treatment of hyperthyroidism, QoL improves. Symptoms of hyperthyroidism, overall QoL and tiredness are among the domains that improve with a high effect size. Notwithstanding, the overall reduction in QoL persists compared to a matched general population, which seems to relate to residual tiredness, mental fatigue and concerns about levothyroxine substitution, ophthalmological symptoms and weight gain. Common factors contributing to reduced QoL in the long term have been described and include a high prevalence of thyroid dysfunction, the psychological burden of chronic illness, TED, possible inability of levothyroxine replacement to restore euthyroidism in all tissues, and central nervous system residual damage and/or dysfunction. The aetiology and treatment modality for hyperthyroidism may also play a role. In addition, a recently highlighted contributor and predictor of poor QoL is excessive weight gain, which given the global epidemic of obesity, mandates further attention. Regarding newer therapies for hyperthyroidism, notably radiofrequency ablation and molecular targeted immunotherapies, there is a dearth of objective data on QoL. New or improved tools for assessing QoL may be needed to better capture all concerns of these patients. There is a need for randomized controlled studies to guide practitioners regarding which pharmacological or non-pharmacological interventions offer the best long-term QoL outcomes in hyperthyroidism. Anti-obesity medications to mitigate weight gain could also be considered for such patients.
Plain language summary: Thyroid overactivity (hyperthyroidism) worsens patients' QoL, which usually improves after treatment. However, QoL is not completely restored for many patients. The reasons are multiple, including excessive weight gain. New approaches in treating hyperthyroidism are needed to address the long-term effects on QoL.
Purpose: Ketosis-prone diabetes (KPD) is a new subtype of diabetes distinct from traditional type 2 diabetes, and the role of muscle mass in KPD remains unclear. Serum creatinine-to-cystatin C ratio (CCR) has been identified as a marker of muscle mass. The present study aims to investigate the value of CCR in newly diagnosed KPD.
Methods: 290 newly diagnosed T2D included into the study were divided into T2D (n=195) and KPD (n=95) group according to the occurrence of ketosis. The cutoff value of CCR in identifying KPD was analyzed by receiver operating characteristic (ROC) curve. Logistic regression was used to assess the relationship between CCR and KPD and the independent influences on KPD.
Results: The serum CCR level of KPD group was significantly higher than that of T2D group. After adjustment for all confounders, the risk of KPD was significantly increased with elevated CCR levels. The optimal cutoff value for CCR were 69.775 for male and 63.365 for female, with areas under the ROC curves of 0.639 in male and 0.648 in female. Postprandial blood glucose and CCR were independent risk factors, whereas age and postprandial C-peptide were independent protective factors for the KPD.
Conclusion: High levels of CCR are significantly associated with the odds of KPD, suggesting that higher muscle mass (estimated by CCR) may be linked to higher KPD incidence. Our study suggests that CCR may be a useful marker for the incidence of KPD, providing new insights into the mechanisms of KPD.
Objective: Primary adrenal insufficiency (PAI) in children, most commonly caused by congenital adrenal hyperplasia (CAH), is challenging to treat due to the short half-life of hydrocortisone and the difficulty in mimicking the physiological rhythm of cortisol. Continuous subcutaneous hydrocortisone infusion (CSHI) has shown benefits in CAH adults but remains poorly studied in children. The aim of our study was to evaluate the feasibility, safety, and clinical efficacy of CSHI in pediatric patients under oral treatment with poorly controlled PAI.
Methods: We conducted a retrospective monocentric study including 13 children and adolescents with PAI who were switched from oral hydrocortisone to CSHI between 2017 and 2024 due to a lack of disease control. Hormonal and clinical parameters were monitored over a median follow-up of 48 months.
Results: The median age at CSHI initiation was 11.08 (7.75-14.08) years. Eleven patients (84.6%) had CAH. The median duration of CSHI was 48 (6-54) months. Biochemical control improved, morning cortisol increased, while ACTH, 17-OHP, androstenedione, and testosterone levels decreased during follow-up. Growth velocity and BMI remained stable. In one patient with prior and recurrent adrenal crises, these events ceased. In boys with testicular adrenal rest tumors, tumor volume decreased or resolved. One adolescent girl with amenorrhea resumed regular menstrual cycles under CSHI. CSHI was well tolerated with no major complications.
Conclusion: CSHI offers a promising therapeutic alternative for children with PAI who are poorly controlled on oral therapy. It provides more physiological cortisol delivery, improves hormonal control, and appears safe during long-term pediatric use. Larger prospective studies are needed to confirm these findings and evaluate quality-of-life outcomes.
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.
Primary hyperparathyroidism (PHPT), increasingly diagnosed in its asymptomatic form, is associated with clinically significant neuromuscular dysfunction. Growing evidence indicates that skeletal muscle is a direct target of parathyroid hormone (PTH), with chronic PTH excess impairing mitochondrial bioenergetics, promoting proteolysis, and altering muscle-bone-adipose endocrine crosstalk. Experimental studies confirm PTH receptor (PTHR1) expression in muscle fibers and satellite cells, while transcriptomic analyses of PHPT muscle reveal dysregulation of calcium signaling and oxidative metabolic pathways. Clinically, patients with PHPT, irrespective of hypercalcemia, demonstrate reduced grip strength, slower gait speed, impaired chair-stand performance, and diminished postural stability. Parathyroidectomy improves several of these deficits, with studies reporting increases in grip strength, knee extension force, ambulatory capacity, and, in some cohorts, improved muscle composition and metabolic gene expression. However, available data are heterogeneous and derived primarily from small cohorts with variable functional measures. Current evidence implicates PTH-mediated skeletal muscle dysfunction as a reversible component of PHPT, yet key mechanistic and clinical gaps remain. Standardized functional assessments and larger prospective studies are needed to clarify biological pathways, identify predictors of postoperative recovery, and inform the integration of muscle health into PHPT management. The focus of this review was to explore evidence linking PTH excess and skeletal muscle pathophysiology and review the relationship between PHPT and parathyroidectomy on physical function.
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.
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