Background:This study evaluates the diagnostic value of serum carcinoembryonic antigen, carbohydrate antigen, neuron-specific enolase, and lipid metabolism markers (total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) in pancreatic neuroendocrine tumors. Methods:A total of 175 pancreatic neuroendocrine tumor patients (experimental group) and 88 healthy individuals (control group) were enrolled. Serum levels of carcinoembryonic antigen, carbohydrate antigen, neuron-specific enolase, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index were analyzed. A logistic regression analysis model was constructed, and the receiver operating characteristic curve was utilized to evaluate the efficacy of individual indicators with statistically significant differences, as well as the combined detection model, in predicting the occurrence, pathological grading, and metastasis of pancreatic neuroendocrine tumors. Results:Pancreatic neuroendocrine tumor patients showed higher levels of carcinoembryonic antigen, neuron-specific enolase, low-density lipoprotein cholesterol and lower levels of high-density lipoprotein cholesterol than the control group. High-grade pancreatic neuroendocrine tumor patients showed higher carcinoembryonic antigen, carbohydrate antigen, neuron-specific enolase, total cholesterol, and low-density lipoprotein cholesterol levels than low-grade cases, with increased metastasis risk. Elevated carcinoembryonic antigen, carbohydrate antigen, and neuron-specific enolase levels were linked to metastasis. The results are statistically significant. High neuron-specific enolase and low high-density lipoprotein cholesterol were pancreatic neuroendocrine tumor risk factors, with area under the curves of 0.899 and 0.666, respectively, improving to 0.911 when combined. Elevated carbohydrate antigen and neuron-specific enolase levels predicted high-grade (area under the curves: 0.728, 0.645; combined area under the curve: 0.765) and metastatic pancreatic neuroendocrine tumors (area under the curves: 0.693, 0.651; combined area under the curves: 0.689). Conclusions:Increased neuron-specific enolase is a strong predictor of pancreatic neuroendocrine tumor occurrence, grading, and metastasis. Lower high-density lipoprotein cholesterol predicts pancreatic neuroendocrine tumor occurrence but not grading or metastasis. Combined markers enhance diagnostic accuracy for pancreatic neuroendocrine tumor detection and grading.
Background:Fibrocalculous pancreatic diabetes is a unique form of diabetes prevalent in tropical regions, characterized by chronic calcific pancreatitis and a high burden of diabetic complications. Sudomotor dysfunction remains underexplored in this population. Aim:To determine the prevalence and clinical determinants of sudomotor dysfunction in individuals with fibrocalculous pancreatic diabetes. Methods:In this cross-sectional study, 90 patients with fibrocalculous pancreatic diabetes were evaluated at a tertiary care endocrinology centre. Sudomotor function was assessed using electrochemical skin conductance. Large fiber neuropathy was evaluated using vibration perception threshold testing and nerve conduction studies. Agreement between modalities was assessed using Cohen's kappa, and logistic regression was used to identify the predictors of sudomotor dysfunction. Results:Sudomotor dysfunction was present in 43.3% of patients, compared with abnormalities in vibration perception threshold (17.8%) and nerve conduction studies (21.1%). Agreement between electrochemical skin conductance and large fiber measures was fair to moderate (κ=0.39-0.47), while the vibration perception threshold and nerve conduction studies showed substantial concordance (κ=0.61). In multivariable analysis, increasing age (odds ratio: 1.08; 95% confidence interval: 1.00-1.16) and longer duration of diabetes (odds ratio: 1.26; 95% confidence interval: 1.07-1.49) were independently associated with sudomotor dysfunction. Conclusions:Sudomotor dysfunction assessed by electrochemical skin conductance was common in fibrocalculous pancreatic diabetes and detected more frequently than abnormalities on vibration perception threshold or nerve conduction studies. Electrochemical skin conductance may serve as a practical adjunctive tool for evaluating sudomotor dysfunction in this population, although longitudinal studies are needed to clarify its clinical significance.
First-degree relatives of patients with type 2 diabetes mellitus may exhibit metabolic abnormalities and subclinical myocardial dysfunction before the onset of overt disease. Left Ventricular Speckle-tracking echocardiography (LV-STE) enables early detection of left ventricular impairment, while osteogenic biomarkers such as osteoprotegerin, osteocalcin, and osteopontin have been linked to cardiometabolic risk. This study aimed to evaluate myocardial strain parameters and serum osteogenic biomarkers in normoglycemic first-degree relatives of patients with type 2 diabetes mellitus.We enrolled 160 normoglycemic participants, comprising 80 individuals with at least one first-degree relative diagnosed with type 2 diabetes mellitus and 80 controls without such a family history. Serum osteocalcin, osteopontin, and osteoprotegerin levels were measured by ELISA. LV-STE was used to assess global longitudinal and circumferential strain from apical four-chamber (A4C), two-chamber (A2C), three-chamber (A3C), and short-axis basal/mid/apical views.Compared with the control group, the study group presented significantly lower mean short-axis basal/mid/apical and A4C/A2C/A3C strain values. The serum osteocalcin level was significantly lower and weakly negatively correlated with the fasting plasma glucose level. osteoprotegerin was positively correlated with LDL-C. No significant associations were found between strain parameters and biomarkers.Normoglycemic first-degree relatives of type 2 diabetes mellitus patients exhibit early myocardial impairment detectable by LV-STE and reduced osteocalcin levels. LV-STE may enhance early risk stratification in this population. Longitudinal studies are needed to determine the prognostic value of osteogenic biomarkers in the progression to type 2 diabetes mellitus and cardiovascular disease.
Aims:To develop and evaluate the German versions of the Diabetes Stigma Assessment Scales for type 1 (DSAS-1) and type 2 diabetes (DSAS-2). Methods:The questionnaires were translated using a standardized translation and back-translation procedure. Adults with type 1 (N=636) and type 2 diabetes (N=177) completed the DSAS-1 and DSAS-2 via an online panel. Factor analyses, internal consistency (Cronbach's α), and correlations with convergent measures and discriminant constructs were conducted to assess reliability and validity. Results:For the DSAS-1, the expected three-factor structure was confirmed; for the DSAS-2, a two-factor solution emerged, although a forced three-factor analysis supported the original structure with minor cross-loadings. Scale consistencies were excellent (DSAS-1: 0.94, DSAS-2: 0.95, and subscales: 0.86-0.93). Both scales showed good concurrent, convergent and discriminant validity. The DSAS-2 showed stronger associations with weight self-stigma and self-esteem than the DSAS-1, consistent with its focus on internalized stigma. Three in four persons (type 1 diabetes: 74% and type 2 diabetes: 72%) endorsed at least one stigma item, mostly related to "blame and judgement." Conclusions:Diabetes stigma constitutes an important psychosocial problem. The German DSAS-1and DSAS-2 are reliable, valid instruments for assessing diabetes stigma. Blame and judgement appeared as the most common form of stigma experienced in this sample.
The methodologyfor diagnosing diabetes mellitus is much more complexthan presented in most national and international guidelines. In the DDG's clinical practice recommendations, the authors therefore update importantdiagnostic parameters annuallyfrom a clinical and especiallyfrom a laboratory medicine point of view, both in the abstractforfast readers as well as in the detailed version (see below).
Abstract:PURPOSE: Primary hyperparathyroidism has been associated with subclinical neuromuscular dysfunction; however, the clinical correlates of muscle strength and morphology in PHPT remain undercharacterized. We hypothesized that muscle dysfunction in primary hyperparathyroidism is reversible after parathyroidectomy and that the reduction in serum calcium predicts early postoperative improvement. Abstract:DESIGN: Prospective observational study conducted at a tertiary care center. Abstract:METHODS: Fifty-three primary hyperparathyroidism patients and 53 age-, sex-, and body mass index-matched healthy controls were assessed using handgrip strength tests, 4-m walking speed, the timed-up-and-go test, and the five-time sit-to-stand test. The muscle thickness was measured via ultrasonography and body composition by bioelectrical impedance analysis. Surgical indications were based on international guidelines for classical primary hyperparathyroidism and on clinical judgment in selected normocalcemic cases. Thirty-four patients underwent parathyroidectomy and were re-evaluated 3 months postoperatively. Generalized linear mixed models were used to identify predictors of changes in muscle function. Abstract:RESULTS: At baseline, patients with primary hyperparathyroidism demonstrated significantly reduced handgrip strength, prolonged durations in the timed-up-and-go and five-time sit-to-stand test tests, and decreased gastrocnemius muscle thickness compared to healthy controls (p<0.05). Following parathyroidectomy, both gastrocnemius muscle thickness and lower limb functional performance (timed-up-and-go and five-time sit-to-stand test) improved significantly. Generalized linear mixed model analysis identified reductions in serum calcium as independent predictors of functional improvement. Vitamin D status was standardized across all participants to minimize confounding and enhance internal validity. Abstract:CONCLUSIONS: Parathyroidectomy in primary hyperparathyroidism patients leads to early improvements in muscle thickness and lower extremity function, suggesting a multimodal recovery process; whether assessment enhances surgical decision-making and patient selection needs to be explored in further studies.
Succinate dehydrogenase (SDH) gene variants are the most common cause of the neuroendocrine tumour hereditary paraganglioma, which is associated with an over 20% metastasis risk as well as significant morbidity. There are currently no relevant human tumour cell lines or mouse models, and molecular understanding of downstream tumourigenic pathways is still rudimentary despite over two decades of concerted effort worldwide. These tumours generally show extremely slow in vivo doubling times (4-12 years), presumably existing in a primarily semi-quiescent state with little cell cycling or DNA replication. This characteristic makes deriving a useful tumour cell line impractical. A better alternative would be a cell line in which cell proliferation can be turned on and off at will, allowing expansion to generate sufficient cell numbers and experimentation once tumour cells have returned to their natural semi-quiescent state. The closest models currently available, highly-proliferating rat and mouse adrenal paraganglioma cell lines, are molecularly unrelated to SDH tumours. In this pilot study, we investigated whether primary SDH-derived paraganglioma tumour cells can be made to proliferate in vitro. We successfully transduced primary paraganglioma tumour cells with a lentiviral construct, using the proven strategy of c-MYC¬T58A (c-MYC) controlled by a Tet-On doxycycline-inducible expression system. We present the first evidence that primary paraganglioma chromaffin cells can be induced to proliferate in vitro, even in later passage cultures. Without any prior selection for chromaffin tumour cells, passaged cultures were obtained with over 80% synaptophysin-expressing chromaffin tumour cells, suggesting that this highly promising strategy deserves further exploration.
Guidelines recommend GLP-1 receptor agonists (GLP-1-RA) and SGLT2-inhibitors (SGLT2i) for individuals with type 2 diabetes (T2D) at high risk of atherosclerotic cardiovascular disease (ASCVD). In the context of precision medicine, we evaluated a personalized treatment algorithm to guide the initial decision between these therapies.Using data from the observational Diabetes Prospective Follow-up registry (Germany/Austria) we studied individuals with T2D who initiated GLP-1-RA (n=1433) or SGLT2i (n=2547) in a multicenter, real-world setting. Baseline characteristics included age, sex, body mass index (BMI), estimated glomerular filtration rate (eGFR), HbA1c, diabetes duration, and history of ASCVD. Non-fatal ASCVD events (myocardial infarction, angina, revascularization, stroke, transient ischemic attack, and peripheral artery disease) were analyzed using dynamic weighted survival modeling to predict the optimal treatment for each individual.The algorithm predicted 48% of individuals to have better ASCVD outcomes with GLP-1-RA and 52% with SGLT2i. GLP-1-RA-optimal individuals had on average a higher BMI (37 vs 31 kg/m2), lower eGFR (71 vs 93 ml/min per 1.73 m2) and less history of ASCVD (9 vs 18%) compared to SGLT2i-optimal individuals. However, an internal model validation showed that the predicted optimal treatment did not statistically significantly prolong the average time to a non-fatal ASCVD event compared to the suboptimal treatment (AFT parameter: 1.13; 95% CI: 0.83-1.56; HR: 0.88; 95% CI: 0.64-1.21).The personalized treatment algorithm for GLP-1-RA and SGLT2i did not result in clear individual ASCVD benefits on either drug, a finding consistent with the clinical equipoise reflected in current T2D treatment guidelines.
Ectopic Cushing's syndrome is a severe endocrine disorder with high morbidity and mortality, making timely diagnosis and effective cortisol control crucial. The aim of this study was to assess the 12-year experience at a tertiary centre.We retrospectively analyzed clinical, biochemical, imaging, treatment, and outcome data in this single-center, non-interventional cohort of patients treated from 2012 to 2024 at the University Hospital Centre Zagreb.Twelve patients were included (10/12 female, 83.3%; median age 43.5 years, range 22-74). Primary tumors were predominantly neuroendocrine (8/12, 66.7%), and 9/12 (75.0%) had metastatic disease at diagnosis. Common features were fat redistribution in 10/12 (83.3%), facial plethora in 8/12 (66.7%), hypertension in 8/12 (66.7%), and peripheral edema in 7/12 (58.3%). Frequent biochemical alterations were hypokalemia in 11/12 (91.7%) and hyperglycemia or new-onset/worsening diabetes in 10/12 (83.3%). Median 24-hour urinary free cortisol was 5,594 nmol/24 h (range: 196-72,954), and ACTH 52.4 pmol/L (range: 8-498). A urinary free cortisol level≥50×the upper limit of normal identified a high-risk group with shorter survival (Spearman ρ=-0.50). Biochemical remission was achieved in 1/12 (8.3%) patient through tumor resection, while the majority required bilateral adrenalectomy (8/12, 66.7%) due to inadequate response to medical therapy or as first-line treatment. At the time of last follow-up, 8/12 (66.7%) patients had died due to disease progression, with a median time to death of 12 months (range: 1-51). The median overall survival was 20 months (range: 1-154).Most patients presented with metabolic disturbances and limited response to medical therapy, leading to bilateral adrenalectomy. Early mortality was driven by uncontrolled hypercortisolism rather than tumor burden, and higher urinary free cortisol was associated with shorter survival. These findings highlight the prognostic relevance of cortisol burden and the importance of prompt cortisol control.
Primary hyperparathyroidism (PHPT) is a prevalent endocrine disorder characterized by disrupted calcium-phosphorus homeostasis. Accurate biochemical assessment, including albumin-corrected calcium, and preoperative localization of parathyroid adenomas are essential for optimal management. This study aimed to evaluate temporal changes in imaging detectability, biochemical markers, and adenoma size, and to assess novel biochemical indices in patients with asymptomatic PHPT (aPHPT).In this multicenter retrospective study, 416 aPHPT patients underwent clinical, biochemical, and radiological evaluation at three time points. Biochemical parameters included albumin-corrected calcium, phosphorus, parathyroid hormone (PTH), 25-hydroxyvitamin D, alkaline phosphatase (ALP), and 24-hour urinary calcium. Novel indices-calcium/phosphorus (Ca/P), PTH/phosphorus (PTH/P), and calcium×chloride/phosphorus (Ca×Cl/P)-were calculated to evaluate diagnostic and predictive value. Imaging included high-resolution neck ultrasonography, 99mTc-sestamibi SPECT/CT, and four-dimensional CT to assess adenoma detectability and size changes. Statistical analyses included repeated-measures ANOVA or Friedman tests for temporal comparisons, correlation analyses, logistic regression for predictors of adenoma detection, and ROC curves to evaluate diagnostic accuracy. A p-value<0.05 was considered significant.Among 416 patients (87% female), ultrasound-detected adenomas decreased over time due to surgery of clearly visible lesions. CT and SPECT/CT initially improved localization, with later decline in CT but continued gains in SPECT/CT. Adenoma size increased, and the PTH/phosphorus ratio changed significantly. Baseline albumin-corrected calcium, phosphorus, and adenoma size predicted radiological detectability, with ROC AUCs of 0.78 for adenoma size and 0.72 for phosphorus. Surgically treated patients exhibited more pronounced biochemical abnormalities and superior CT-based localization.Following imaging and biochemical assessments, including albumin-corrected calcium, improve detection, monitoring, and management of aPHPT. Novel indices such as PTH/phosphorus and Ca/P ratios provide practical, low-cost tools for early disease identification and risk stratification. Integrating dynamic biochemical markers with imaging supports individualized, evidence-based clinical decision-making.
The human KISS1 gene encodes the hypothalamic Kisspeptin, which is released in a pulsatile manner and binds the KISS1 receptor, that is located on gonadotropin releasing hormone neurons. This interaction ensures pulsatile gonadotropin releasing hormone secretion leading to induction of the hypothalamic-pituitary-gonadal axis and by this controls puberty onset. Disruption of this process is associated with hypogonadotropic hypogonadism. We identified a novel heterozygous KISS1 variant c.-7C>T in two brothers diagnosed with hypogonadotropic hypogonadism. The mutation affects the Kozak consensus sequence of the KISS1 gene and potentially interferes with KISS1 gene expression. Consequently, this affects the hypothalamic-pituitary-gonadal axis resulting in hypogonadotropic hypogonadism. In both patients, complete development of primary and secondary male sex characteristics and stabilization of serum sex steroid hormone levels was achieved by testosterone therapy. Additionally, human chorionic gonadotropin and follicle stimulating hormone combination therapy in the older brother (patient 1) induced spermatogenesis and enabled fatherhood. Apart from this, we identified the heterozygous CHD7 variant c.2690G>A in the younger brother (patient 2). However, the contribution of this variant to the pathogenesis of hypogonadotropic hypogonadism remains elusive.
Abstract:BACKGROUND: Neuropathic pain is a frequent and disabling complication of type 2 diabetes mellitus. Although poor glycemic control is known to contribute to diabetic neuropathy, its specific relationship with painful manifestations remains incompletely characterized. Abstract:OBJECTIVE: The aim of this study was to evaluate the association between hemoglobin A1c levels and the presence of neuropathic pain in patients with type 2 diabetes mellitus. Abstract:METHODS: A cross-sectional analytical study was conducted in 172 adults with type 2 diabetes mellitus attending outpatient clinics at a tertiary hospital in northern Peru. Neuropathic pain was assessed using the validated Spanish version of the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. Glycemic control was evaluated using hemoglobin A1c, analyzed both as a continuous variable and a dichotomous variable at 7%. Clinical, metabolic, and demographic variables were compared between patients with and without neuropathic pain. Associations were examined using Poisson regression with robust variance and logistic regression, estimating crude and adjusted effect measures with 95% confidence intervals. Abstract:RESULTS: Neuropathic pain was identified in 50% of participants. Patients with neuropathic pain showed higher hemoglobin A1c values and a greater proportion of values equal to or above 7%. In adjusted models, elevated hemoglobin A1c levels remained independently associated with neuropathic pain, when analyzed both as a dichotomous variable and as a continuous variable. Dyslipidemia and hypertension also showed independent associations. Abstract:CONCLUSIONS: Higher hemoglobin A1c levels are independently associated with neuropathic pain in patients with type 2 diabetes mellitus, underscoring the importance of sustained glycemic control.
Uric acid-to-high-density lipoprotein cholesterol ratio (UHR) is a novel and promising marker for metabolic abnormalities. Recent studies have demonstrated that UHR is related to a number of diseases that are caused by insulin resistance. However, only a few studies have investigated the association between UHR and insulin resistance. The aim of this study was to evaluate the diagnostic ability of UHR to detect insulin resistance in healthy normoglycaemic and normoinsulinaemic men.A total of 209 healthy men (aged 23-57 years) with normoglycaemia and normoinsulinaemia were included in this study. Anthropometric and biochemical data were collected. Insulin resistance was assessed by original homeostasis model assessment of insulin resistance (HOMA-IR) and its computerized updated version (HOMA2-IR), the fasting glucose/insulin ratio (FGIR), the McAuley index, and the triglyceride-glucose (TyG) index. A receiver operating characteristic (ROC) curve analysis was conducted to evaluate the ability of UHR to predict insulin resistance.UHR was significantly correlated with HOMA-IR (rs=0.23; p=0.001) and HOMA2-IR (rs=0.20; p=0.003). There were no correlations between UHR and other insulin resistance indices. The prevalence of insulin resistance among the participants was 21.5% and 9.6% according to HOMA-IR (>2.7) and HOMA2-IR (>1.8) cut-off values, respectively. ROC curve analysis revealed the diagnostic ability of UHR to determine insulin resistance assessed by HOMA2-IR (area under the ROC (AUROC) curve: 0.680; p=0.005). However, UHR did not predict insulin resistance assessed by HOMA-IR (AUROC curve: 0.584; p=0.087).UHR is not a reliable marker of insulin resistance in healthy men with normoglycaemia and normoinsulinaemia.
The study aimed to assess sympathetic (SNS) and parasympathetic (PSNS) activity in individuals with obesity and different states of prediabetes and to assess their associations with markers of inflammation.A total of 104 participants (mean age 46.7±10.3 years; mean body mass index (BMI) 31.5±6.3 kg/m2) were categorized into three age- and BMI-matched groups based on glucose tolerance: 1) with normal glucose tolerance (n=20); 2) with high 1-h plasma glucose > 8.6 mmol/l (n=25) 3) with impaired glucose tolerance (n=59). All participants underwent an oral glucose tolerance test, and the area under the curves for glucose, insulin, and C-peptide were calculated. Creatinine (CKD-EPI calculation), lipids, glycated haemoglobin, and inflammatory markers (C-reactive protein (CRP), serum amyloid A, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6 (IL-6), IL-8, and tumor necrosis factor-α) levels were measured. Body composition was assessed by bioimpedance analysis. Tissue advanced glycation end-products (AGEs) were evaluated by AGE-Reader. Autonomic function was measured with the АNX-3.0 autonomic monitoring system.A progressive decline in resting and stimulated PSNS and SNS activity was observed with worsening glucose tolerance. Some of the inflammatory markers were numerically elevated in prediabetic stages. After adjustment for age, there was a reciprocal relationship between PSNS and SNS tone and CRP (r=-0.23 to-0.40, all p<0.025). An independent inverse relationship was found between PSNS tone and systolic blood pressure and CRP. However, after adjustment for BMI and/or body composition parameters, waist circumference was the only independent predictor of PSNS activity (p<0.0001), explaining 26% of its variation.This study demonstrates an inverse relationship between PSNS activity and both systolic blood pressure and CRP levels, though this association is largely mediated by visceral obesity.
Fibrosis-Index-4 (FIB-4) is used with a cut-off of 1.3 to exclude severe fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study was to examine the potential association of FIB-4 with chronic vascular complications of type 2 diabetes mellitus (T2DM). Included were 550 adults (271 men) with T2DM, mean age of 67.88±11.46 years and median T2DM duration of 15 (9.75-22) years. FIB-4 was calculated and chronic vascular complications were recorded. Participants with FIB-4>1.3 were compared with those having FIB-4≤1.3. The former exhibited significantly more frequent peripheral neuropathy (corrected odds ratio [cOR]: 26.48, 95% confidence interval [CI]: 16.81-41.71, p<0.001), chronic kidney disease (cOR: 33.75, 95% CI: 19.55-58.28, p<0.001), retinopathy (cOR: 22.42, 95% CI: 14.22-35.34, p<0.001), stroke (cOR: 2.85, 95% CI: 1.56-5.21, p<0.001), coronary artery disease (cOR: 6.20, 95% CI: 4.25-9.04, p<0.001) and peripheral arterial disease (cOR: 4.60, 95%-CI: 2.62-8.07, p<0.001) than the latter. Peripheral neuropathy was staged as absent, mild and moderate-severe, based on the Neuropathy Disability-Score (NDS). FIB-4 score was associated with increased clinical severity of peripheral neuropathy (p<0.001).
The existing literature on the effects of semaglutide in people with HIV (PWH) and diabetes mellitus remains limited. In this study, the effects of semaglutide on weight control and inflammation in PWH were evaluated.This is a prospective observational study that included PWH with type 2 diabetes mellitus monitored at the HIV Unit of the University General Hospital of Alexandroupolis and a matched control group of non-HIV individuals. Demographic, anthropometric, and clinical characteristics, including HIV-related data and comorbidities, were reported. All participants received semaglutide with a gradual dose increase to 1 mg once weekly. Body Mass Index (BMI), glycosylated haemoglobin (HbA1c), and inflammatory markers (IL-6, TNF, hsCRP, sCD14, CD4/CD8 ratio) were recorded at baseline and at 6, 12, 18, and 24 months.Fifty participants (PWH: n=25; non-HIV: n=25) were included. At baseline, the mean BMI was 35.2±8.0 kg/m2 for PWH and 36.1±6.0 kg/m2 for non-HIV controls. Semaglutide treatment resulted in significant and sustained weight loss in both groups (p<0.001). At 24 months, the median weight loss was -14.6 kg in the PWH group and -18.8 kg in the non-HIV group for those with a baseline BMI>35 kg/m2. Glycemic control also improved significantly, with mean HbA1c decreasing from 7.7%±1.23 to 5.2%±1.02 in PWH (p<0.001), and from 7.9%±1.16 to 5.6%±1.21 in non-HIV controls (p<0.001). Significant reductions were observed in hsCRP and sCD14 levels in both cohorts. A unique finding was the significant increase in the CD4/CD8 ratio in the PWH group, from a mean baseline of 0.54±0.12 to 0.83±0.14 at 24 months (p<0.001), a change not seen in the non-HIV controls.Semaglutide appears to be an effective and safe option for weight reduction and inflammation control in PWHIV. Further studies with a larger number of patients are necessary to substantiate these findings.
