Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association最新文献

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).

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 (r_s=0.23; p=0.001) and HOMA2-IR (r_s=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.

In lean humans, cold-activated brown adipose tissue (BAT) is associated with improved insulin sensitivity and lipid metabolism. Metabolic consequences of acute cold exposure in obesity are less well characterized. We studied the effects of acute cold-activated BAT on markers of metabolic health in men with obesity but no other chronic diseases and aimed to characterize potential underlying mechanisms linked to cold exposure. Fourteen young (mean age [±standard error of the mean]: 26.4±0.8 y) males with obesity (body mass index [BMI] 31.9±0.5 kg/m²; range: 30.4-35.6 kg/m²) participated in a randomized cross-balanced within-subject study with two experimental conditions, i.e., i) cold exposure (CE), using a water-perfused suit at 16.0°C, shivering excluded for in total 5 h; and ii) thermoneutrality (TN), using the same water-perfused suit at 25°C. Lipid metabolism and relevant hormone levels were measured. Glucose tolerance, β-cell secretion, and insulin sensitivity were assessed by the Botnia clamp. Expression profiles of selected genes regulating lipolytic and β-oxidation pathways were determined from peripheral blood mononuclear cells.Upon CE, plasma noradrenaline levels increased relative to TN. CE decreased fasting glucose and improved glucose tolerance in parallel with increased β-cell response. Moreover, CE led to increased plasma triglycerides as well as expression levels of selected genes involved in lipid metabolism.The observed metabolic changes and increased gene expression regulating lipid transport and disposal point towards a cold-induced insulin feedback signal required to sustain BAT thermogenesis demands. Our study reveals acute metabolic effects of thermogenically activated BAT and potential mediating mechanisms in young men with obesity.

Regulators of G protein signaling (RGSs) are key modulators of β-cell function and stress adaptation. Similarly, circadian clock components are intricately implicated in the regulation of insulin secretion and β-cell physiology. However, their responses to sustained cellular stimulation under depolarizing conditions remain incompletely understood. MIN6 cells were subjected to prolonged potassium chloride (KCl) exposure to induce sustained membrane depolarization, mimicking conditions of chronic β-cell stimulation. The expression levels of RGSs and core clock genes were analyzed, and associated changes in cellular stress and differentiation markers were assessed.KCl treatment led to the upregulation of endoplasmic reticulum (ER) stress markers, including C/-EBP homologous protein (CHOP) and activating transcription factor 4 (ATF4), with no induction of oxidative stress. Expression of RGS2, RGS4, and RGS16 was elevated. RGS2 partially co-localized with eukaryotic initiation factor-2α (eIF2α), suggesting a role in translational control during stress. Furthermore, KCl-induced depolarization was associated with characteristic changes in β-cell differentiation markers and disallowed genes, indicative of a dedifferentiation-like state. Transcript levels of several circadian genes were altered, including significant downregulation of D-site binding protein (DBP) and upregulation of its repressor E4-binding Protein 4 (E4BP4). Notably, differentiated embryo-chondrocyte expressed gene-1 (DEC1), a clock gene known to be inducible by various external stimuli, was also upregulated, suggesting broader circadian disruption under depolarizing conditions.Sustained membrane depolarization induces ER stress and transcriptional remodeling in MIN6 β-cells, including the modulation of RGS proteins and key circadian regulators such as DBP, E4BP4, and DEC1. These alterations may contribute to functional impairment and a dedifferentiation-like state of β-cells under chronic stimulatory conditions.

Introduction: The existing literature on the effects of semaglutide in people with HIV (PWH) and diabetes mellitus remains limited. The aim of the present study is to evaluate the effect of semaglutide on weight control and inflammation in PWH.

Patients and methods: 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 hemoglobin (HbA1c), and inflammatory markers (IL-6, TNF, hsCRP, sCD14, CD4/CD8 ratio) were recorded at baseline and at 6, 12, 18, and 24 months.

Results: A total of 50 participants (PWH: n=25; non-HIV: n=25) were included. At baseline, the mean BMI was 35.2±8.0kg/m2 for PWH and 36.1±6.0kg/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 >35kg/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.

Conclusion: 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.

Sodium-glucose co-transporter inhibitors significantly reduce cardiovascular mortality, hospitalization for heart failure, and improve renal outcomes regardless of diabetes status. This study investigated the effect of empagliflozin on plasma biomarkers to explore underlying mechanisms.Adult patients with type 2 diabetes and heart failure with either left ventricular ejection fraction≤45% (EFFORT-1) or>45% (EFFORT-2) were recruited. Patients received 25 mg empagliflozin or placebo for 48 weeks. Plasma levels of endothelin-1, galectin-3, insulin-like growth factor binding protein-7, and kidney injury molecule-1 (KIM-1) were measured at baseline and at weeks 2, 12, 24, and 48. A total of 63 patients were recruited, 24 in EFFORT-1 and 39 in EFFORT-2. Empagliflozin significantly reduced KIM-1 levels by 38% at week 48 in EFFORT-2 compared with placebo (95% confidence interval: -57%, -13%). No significant impact on other biomarkers was observed.Empagliflozin demonstrated, as shown by the decrease in KIM-1 levels, a renal tubular protective effect in heart failure patients with type 2 diabetes.

This study retrospectively evaluates the risk of chronic kidney disease (CKD) progression in patients with type 2 diabetes and mild-to-moderate reduction in the estimated glomerular filtration rate (eGFR).Sixty-six patients with type 2 diabetes and an eGFR between 45 and 60 mL/min/1.73 m² were included, from April 1, 2014, to March 31, 2015, with an 8-year follow-up ending on March 31, 2023. Baseline clinical parameters, including the body mass index, blood pressure, and biochemical markers, were recorded. The HbA1c and eGFR levels were measured annually. The eGFR slope (mL/min/1.73 m²/year) was used to evaluate the CKD progression.Patients with a negative eGFR slope (n=40) exhibited significantly greater HbA1c fluctuations and a higher coefficient of variation (CV) compared with those with an eGFR decline (P=0.011 for both) and were also markedly older (P=0.049). Logistic regression analysis showed a significant association between each one standard deviation increase in the CV and eGFR decline (odds ratio, 1.99; P=0.041), whereas the HbA1c fluctuation showed a trend toward association.Greater variability in glycemic control is linked to an increased risk for CKD progression in type 2 diabetes with mild-to-moderate kidney dysfunction.

Sitagliptin, an inhibitor of dipeptidyl peptidase-4 widely used in type 2 diabetes therapy, impairs the barrier formed by retinal endothelial cells (REC) during prolonged exposure. Because diabetic macular edema is treated with inhibitors of vascular endothelial growth factor (VEGF)-A signaling, we now studied (1) if sitagliptin interfered with this therapeutic approach and (2) if VEGF-A is involved in sitagliptin-induced barrier dysfunction.Confluent immortalized bovine REC (iBREC) were exposed for two days to sitagliptin and/or tivozanib, an inhibitor of the VEGF receptor 2, with or without VEGF-A. The cell index as an indicator of permeability was continuously measured, and cells and supernatants were harvested. Expressions of regulators of para- and transcellular flow, i.e., claudin-1, claudin-5, and plasmalemma vesicle-associated protein (PLVAP), were determined by subsequent Western blot analyses, and potential secretion of VEGF-A was measured by ELISA.Sitagliptin-exposed iBREC did not secrete VEGF-A, and, accordingly, tivozanib did not prevent the sitagliptin-induced decline of the cell index and the increased expression of tight junction (TJ) protein claudin 1. More TJ-protein claudin-5 was isolated together with proteins from membranes or organelles from sitagliptin-treated iBREC, which did not express PLVAP. The VEGF-A₁₆₅-induced declines of the cell index and TJ-protein claudin-1 were prevented by tivozanib, and this process was not modulated by sitagliptin.The underlying mechanisms of barrier dysfunctions caused by sitagliptin or VEGF-A are different and independent. Most importantly, the DPP-4 inhibitor does not interfere with blocking VEGF signaling to correct VEGF-A-dependent barrier dysfunction.

Diabetic peripheral neuropathy (DPN) is one of the most frequent complications of diabetes mellitus (DM). This brief narrative review discusses the relationship between DPN and balance impairment. DPN may alter movement perception as a result of diminished proprioceptive and cutaneous input from skin, muscles and joints, leading to balance impairment. In everyday practice, diagnosis of impaired balance relies on a combination of clinical history, physical examination and functional tests, such as the Timed Up and Go test or the Berg Balance Scale, as well as instrumental assessments where available. Therapeutic principles include optimised glycaemic control and management of vascular risk factors for the prevention and management of DPN. While these measures do not directly improve balance, they may contribute to better postural stability by preserving peripheral nerve function, reducing the progression of neuropathic deficits, and maintaining muscle strength. In addition, general exercises for balance improvement, physiotherapy, and focused and specialised strengthening, stretching and functional training programmes may improve static and dynamic balance. Finally, electric stimulation has demonstrated positive results in improving postural stability in DPN.