INTRODUCTION: Sarcopenic obesity is closely related to the occurrence of metabolically associated fatty liver disease (MASLD), but the factors that influence the effectiveness of dietary supplements in increasing muscle mass have not yet been clarified. OBJECTIVE: In our study, we examined the effects of a diabetes-specific dietary supplement containing beta-hydroxy-beta-methylbutyrate (HMB) on total body muscle mass after a treatment lasting for 6 months, and measured by densitometry in patients with type 2 diabetes who were treated for sarcopenic obesity and also met the criteria of MASLD. Then, we looked for linear correlations between the degree of muscle mass change and age, as well as the lean mass index, and various metabolic parameters such as hemoglobin A1c, C-peptide, and triglyceride levels. Our goal was also to determine the predictive value of these parameters in forecasting of the effectiveness of the dietary supplement. METHOD: Our cross-sectional study included 48 patients with type 2 diabetes (aged 55-84 years, 40 female and 8 male, average age 72.48 ± 8.26 years). As a control group, we chose 20 persons of similar age with no serious comorbidities, who had neither diabetes nor MASLD. We confirmed liver steatosis using transient elastography. After identifying the relationships between the degree of muscle mass change and other examined parameters using simple linear regression, we evaluated the predictive value of individual parameters for the extent of muscle mass change with logistic regression. RESULTS: The average pre-treatment values of patients' parameters were: body mass index: 27.80 ± 4.63, hemoglobin A1c: 6.27 ± 0.73, degree of steatosis: 289 ± 42 dB/m, appendicular muscle mass index: 6213 ± 786 g/m², android fat ratio: 47.59 ± 9.80%, total fat ratio: 41.82 ± 9.31%. After a 6-month treatment, we observed an increase in muscle mass in 28 patients. Of those, the increase reached up to 5% of the original muscle mass in 16 patients, it was above 5% in 8 patients, and it exceeded 10% of the original mass in 4 patients. We observed a slight decrease in muscle mass in 20 patients, with the decrease reaching up to 5% of the original muscle mass in all of them. We found a significant positive linear relationship between the degree of muscle mass increase and other baseline parameters in terms of C-peptide (r = 0.42, p = 0.03) and alkaline phosphatase (r = 0.51, p = 0.01), and a negative relationship in terms of age (r= -0.39, p = 0.05) and triglycerides (r = -0.41, p = 0.04). We did not find a significant relationship with any body composition parameter. Based on the logistic regression analysis, the predictors of muscle mass change were as follows: age appeared as a negative predictor (OR = 0.87, CI: 0.77-0.99, p = 0.04), and triglycerides appeared as a borderline negative predictor (OR = 0.21, CI 0.04-1.03, p = 0.05). CONCLUSION: Taking HMB-containing dietary supplements led to an increase or maintenance of muscle mass in a significant portion of patients; however, the changes in muscle mass did not reach the level of statistical significance, although individual responses to the intervention varied, with higher age and higher triglyceride levels having a negative impact. So, in this regard, the conclusion of the study can be considered as negative. Interpretation of these results is limited by the small number of participants and the cross-sectional nature of the study, hence larger prospective studies are needed to confirm them. Orv Hetil. 2026; 167(38): 1507-1515.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, yet approved pharmacotherapies remain limited. The ovarian tumor domain-containing protein 1 (OTUD1) has been implicated in metabolic regulation, but its role in MASLD remains unclear. OTUD1 expression was significantly elevated in liver samples from patients with MASLD and in high-fat diet (HFD)-fed mice, a finding further supported by two independent Gene Expression Omnibus (GEO) cohorts (GSE24807 and GSE126848). Studies using systemic Otud1-knockout mice showed that Otud1 deficiency markedly alleviated insulin resistance and inflammation under HFD and high-fat, methionine-restricted, choline-deficient (HFMCD) diet conditions. To assess the hepatocyte-specific and therapeutic relevance of OTUD1, Otud1 was silenced in hepatocytes using AAV8-TBG-shOtud1, which significantly ameliorated HFMCD-induced steatohepatitis. Mechanistically, integrated interactome analyses identified heat shock protein 90α (HSP90α) as a direct substrate of OTUD1. OTUD1 bound to HSP90α and removed its K48-linked polyubiquitin chains at K283, thereby preventing its proteasomal degradation and enhancing its stability. This effect was required for OTUD1-driven lipid accumulation in hepatocytes, as the catalytically inactive OTUD1-C320S mutant failed to stabilize HSP90α or promote lipid deposition. Transcriptomic profiling further revealed that OTUD1 overexpression activated lipid metabolism and inflammatory pathways in OA/PA-treated LO2 cells. Together, these findings identify OTUD1 as a previously unrecognized driver of MASLD progression through the OTUD1-HSP90α axis and suggest that OTUD1 may serve as a potential therapeutic target for metabolic liver disease.

Given that alpinetin possesses hypoglycemic and cardioprotective properties, it holds potential for co-administration with the antidiabetic agent glimepiride. The aim was to evaluate the impact of alpinetin on the pharmacokinetics and hypoglycemic efficacy of glimepiride, thereby providing a foundation for the development of alpinetin and informing its potential clinical translation. Pharmacokinetic studies were performed in rats following oral administration of glimepiride (1 mg/kg) alone or combined with alpinetin (30 mg/kg). The effect of the combination of glimepiride and alpinetin on blood glucose levels was investigated in a rat model of type 2 diabetes mellitus (T2DM). In vitro experiments were conducted to evaluate the effect of alpinetin on glimepiride metabolic stability and to assess its role on cytochrome P450 2C9 (CYP2C9) activity. Co-administration of glimepiride with alpinetin resulted in significant changes in the pharmacokinetics of glimepiride, as evidenced by an increase in area under the concentration-time curve (AUC), elimination half-life (), maximum concentration (C), and a decrease in clearance. Glimepiride in combination with alpinetin enhanced the hypoglycemic effect in T2DM rats. Mechanistic studies in liver microsomes revealed that alpinetin improved glimepiride metabolic stability and inhibited CYP2C9 activity. The combination of glimepiride with alpinetin may increase the systemic exposure of glimepiride through inhibition of CYP2C9 activity. This likely contributes to the enhanced hypoglycemic effect observed, but also underscores the need for caution regarding the potential risk of hypoglycemia.

Primary cutaneous cryptococcosis (PCC) is a rare infection caused by direct inoculation of through disrupted skin. We report a 52-year-old male farmer with type 2 diabetes but no HIV infection or known major immunosuppressive disease who developed chronic refractory ulcers on the right forearm following suspected insect-bite trauma. was isolated from cutaneous specimens. Probe-capture metagenomic next-generation sequencing (MetaCAP) of the ulcer tissue additionally detected at 202 reads per million (RPM), accounting for 91.98% of the fungal sequences, with a reported confidence of 99%. Histopathology demonstrated an infectious granuloma, while bacterial culture identified methicillin-resistant and extended-spectrum β-lactamase-producing . Chest computed tomography and cerebrospinal fluid investigations did not support pulmonary or central nervous system cryptococcosis. Liposomal amphotericin B was discontinued because of acute kidney injury, and subsequent fluconazole plus flucytosine treatment resulted in reduced exudation, granulation tissue formation, and partial ulcer healing. PCC should be considered in chronic post-traumatic ulcers, with systematic evaluation for extracutaneous involvement before establishing a primary cutaneous diagnosis.

BACKGROUND: Overweight status, obesity, and diabetes represent significant socioeconomic burdens that require long-term management. METHODS: To evaluate the efficacy and safety of dual-agonist CagriSema vs semaglutide monotherapy, cagrilintide monotherapy, and placebo in adults with overweight/obese status and type 2 diabetes, we searched Embase, MEDLINE, PubMed, and the Cochrane Library up to 14 June 2026 for randomized controlled trials (RCTs). Separate pairwise meta-analyses were conducted using random effects models. RESULTS: Eight RCTs comprising 6898 participants were included. CagriSema was associated with significantly greater percentage body weight reduction compared to semaglutide [MD -6.60%; 95%CI: -8.51 to -4.68; P<0.0001; I =82%], cagrilintide [MD -8.15%; 95%CI: -11.40 to -4.89; P<0.0001; I =95%], and placebo [MD -14.30%; 95%CI: -17.41 to -11.19; P<0.0001; I =99%]. A greater decrease in the percentage of glycated hemoglobin was also observed for CagriSema than for semaglutide [MD -0.09%; 95%CI: -0.14 to -0.04; P=0.0004; I =39%], cagrilintide [MD -0.87%; 95% CI -1.48 to -0.26; p = 0.005; I = 97%], and placebo [MD -1.55%; 95% CI -2.14 to -0.97; p < 0.0001; I = 99%]. Furthermore, CagriSema achieved significantly greater reductions in absolute body weight, waist circumference and body mass index across all comparators (all p < 0.0001). CagriSema demonstrated better blood pressure control compared with cagrilintide and placebo, with effects comparable to those of semaglutide. Moreover, CagriSema significantly decreased C-reactive protein and improved lipid profiles compared with cagrilintide and placebo. CagriSema increased any adverse events and gastrointestinal adverse events compared with all comparators. Substantial statistical heterogeneity was observed in several continuous outcomes, driven by diverse baseline clinical characteristics and background therapies. CONCLUSION: Compared with current standard monotherapies and placebos, CagriSema demonstrates superior weight loss, glucose, and lipid control. Key limitations include the relatively small number of eligible trials and the current lack of long-term cardiovascular endpoints.

PURPOSE: Obesity is a significant risk factor for diabetic kidney disease (DKD). However, the relationship between obesity-related indicators and DKD is controversial. The aim of this study was to investigate the gender-specific differences in predictive performance of eight obesity-related indicators concerning DKD risk among type 2 diabetes mellitus (T2DM) patients. METHODS: This cross-sectional study analyzed data from 1586 T2DM patients aged 18-80 years. The exposure variables included body mass index (BMI), triglyceride-glucose index (TyG), Chinese visceral adiposity index (CVAI), visceral adiposity index (VAI), and TyG-related composite indicators, which are TyG-waist circumference (TyG-WC), TyG-body mass index (TyG-BMI), TyG-waist-hip ratio (TyG-WHpR), and TyG-waist-height ratio (TyG-WHtR). Point-biserial correlation analysis, multivariate logistic regression, receiver operating characteristic (ROC) curve, subgroup analyses, and interaction tests were used to explore the correlation between these indicators and DKD. RESULTS: The prevalence of DKD in the studied T2DM patients was 37.3%. All eight obesity-related indicators were independently and positively associated with DKD. TyG-BMI had the largest AUC (0.6195) for predicting DKD in males, with a cut-off value of 53.3250. TyG-WHtR had the highest AUC (0.6213) for DKD in females, with a cut-off value of 1.0234. TyG-WHtR was more strongly associated with DKD in T2DM patients with systolic blood pressure (SBP) ≥ 140 mmHg, according to subgroup analysis (P for interaction = 0.0265). CONCLUSION: The optimal predictors of DKD in T2DM patients were gender-specific: TyG-BMI in males and TyG-WHtR in females. TyG-WHtR should be closely monitored in female T2DM patients (especially those with SBP ≥ 140 mmHg) to enable early identification and intervention for DKD risk. These gender-specific indices may provide preliminary evidence for early DKD risk stratification.

BACKGROUND: Multi-vessel coronary artery disease (MVCD), defined as stenosis affecting ≥2 major coronary arteries, confers poor clinical outcomes in patients with coronary artery disease (CAD). Cytochrome P450 2C19 (CYP2C19) CYP2C19 participates in lipid metabolism and inflammatory regulation, which may be associated with individual variations in the severity of coronary artery lesions. This study aimed to explore the clinical and genetic factors associated with MVCD focusing on polymorphisms and chronic metabolic diseases. METHODS: This single‑center cross‑sectional study enrolled 4124 patients with angiographically confirmed CAD, who were divided into single‑vessel CAD (n=846) and MVCD (n=3278) groups. Baseline clinical data and genotypes were collected. The chi-square test, Hardy-Weinberg equilibrium test, and logistic regression analyses were performed for statistical evaluation. RESULTS: Higher prevalences of hypertension, type 2 diabetes mellitus, and dyslipidemia were observed in MVCD patients. CYP2C19*2 (rs4244285, 681G>A) and *3 (rs4986893, 636G>A) allele frequencies were markedly elevated in the MVCD group. Logistic regression analysis confirmed that hypertension (odds ratio (OR)=1.485, 95% confidence interval (CI): 1.267‑1.740, <0.001), T2DM (OR=2.441, 95% CI: 2.006‑2.970, <0.001), dyslipidemia (OR=1.313, 95% CI: 1.097‑1.572, =0.003), and CYP2C19 poor metabolizer (*2/*2, *2/*3 and *3/*3 genotypes) status (OR=1.744, 95% CI: 1.360‑2.237, <0.001) was independently associated with MVCD. The combined impaired CYP2C19 metabolic phenotype (intermediate (*1/*2 and *1/*3 genotypes) plus poor metabolizers) was also independently correlated with MVCD (adjusted OR=1.285, 95% CI: 1.095-1.508, =0.002). CONCLUSION: Clinical metabolic comorbidities and the combined impaired CYP2C19 metabolic phenotype are associated with MVCD. These findings may provide valuable reference for risk assessment of severe CAD.

PURPOSE: To evaluate the diagnostic performance of fundus autofluorescence (FAF) imaging for detecting diabetic macular edema (DME) using swept-source optical coherence tomography (SS-OCT) as the reference standard, and to identify metabolic factors associated with FAF detection accuracy in patients with type 2 diabetes mellitus. PATIENTS AND METHODS: This cross-sectional diagnostic accuracy study enrolled 120 eyes from 68 patients with type 2 diabetes mellitus at the Vitreoretina Subdivision, Department of Ophthalmology, RSUP Dr. Mohammad Hoesin, Palembang, Indonesia, between January 2024 and June 2025. All participants underwent comprehensive ophthalmic examination including FAF imaging and en face SS-OCT (DRI OCT Triton Plus, Topcon). Metabolic parameters including glycated hemoglobin (HbA1c), fasting lipid profile, body mass index (BMI), estimated glomerular filtration rate (eGFR), and diabetes duration were recorded. Diagnostic accuracy indices were calculated using 2×2 contingency tables. Multivariate logistic regression identified metabolic predictors of FAF detection concordance with SS-OCT. RESULTS: DME was present in 78 eyes (65.0%) by SS-OCT. FAF demonstrated sensitivity of 73.1% (95% CI: 61.8-82.5%), specificity of 76.2% (95% CI: 61.5-87.2%), positive predictive value of 85.1%, negative predictive value of 60.4%, positive likelihood ratio of 3.07, negative likelihood ratio of 0.35, and diagnostic odds ratio of 8.68. HbA1c ≥8.5% (OR 3.42, 95% CI: 1.28-9.14, p=0.014), diabetes duration ≥10 years (OR 2.87, 95% CI: 1.15-7.16, p=0.024), and BMI ≥30 kg/m (OR 2.31, 95% CI: 0.94-5.68, p=0.068) were independently associated with FAF-OCT concordance. Center-involved DME showed higher FAF sensitivity (82.4%) compared to non-center-involved DME (55.6%, p=0.012). CONCLUSION: FAF imaging demonstrates moderate diagnostic accuracy for DME detection, with performance significantly influenced by metabolic status and DME subtype. Integration of metabolic risk stratification may optimize FAF-based screening in diabetic populations.

Olanzapine is an atypical antipsychotic drug associated with a high risk of weight gain and metabolic disorders. This condition represents both a major health risk for patients and a therapeutic challenge in psychiatric care. We present a series of four cases exhibiting a rapid and severe weight gain under olanzapine treatment, as well as new-onset metabolic syndrome in three of them. The evolution of these disorders after treatment modification is presented for three cases, and strategies for mitigating the risk of metabolic complications in patients receiving antipsychotic drugs are discussed.

Lifestyle medicine (LM) provides a high-value framework for treating and potentially reversing chronic diseases, such as type 2 diabetes (T2D), obesity, cardiovascular diseases, and some cancers. Yet, the field of LM is still growing, and few examples exist of how to successfully implement LM into clinical care. This paper describes the implementation of 1:1 lifestyle medicine (LM) coaching visits for 45 patients with uncontrolled type 2 diabetes (T2D), (mean HbA1c 10.5%) and on multiple diabetes medications, at Cone Health's Reidsville Endocrinology practice in North Carolina, USA. In brief, during routine endocrinology visits, the lead physician of the LM program at Cone Health, who is trained in LM, identified patients with uncontrolled T2D where scheduling allowed him to fit in some additional time for coaching. Forty-five interested patients selected over a period of several weeks from Spring of 2022 to Fall of 2022 made the first cohort. During a typical LM encounter, immediately after addressing their referral concerns with a routine endocrinology consult, verbally consenting patients were personally invited to learn more about LM. They were provided with a packet of materials focused predominately on prescribing nutrition and exercise as treatment for chronic disease. The physician spent an additional 10-15 minutes with each verbally consenting patient to go through selected materials in the packet, focusing largely on nutrition and physical activity, and successfully billed for the additional time. The patients were encouraged to take the packet home for further learning and return to their next routine visits with questions and to engage in further coaching. Following this brief but intensely focused coaching session which was done in addition to the routine endocrinology visit, lifestyle medicine coaching was able to be incorporated into subsequent, routine endocrinology visits in many of the initially identified patients. The majority of these patients also accepted a referral to a dietitian in the same practice. This experience highlights a model for potentially integrating LM coaching into routine practice and, consistent with previous research, highlights the importance of a site champion for successful LM implementation. Future research is needed to formally assess the success of coaching visits, particularly in terms of assessing health outcomes in patients who engaged in the 1:1 coaching.

BACKGROUND: Melioidosis is a tropical infectious disease caused by Burkholderia pseudomallei. Although vascular involvement is rare, melioidosis-associated abdominal aortic pseudoaneurysm can rapidly progress and carries a high risk of rupture and mortality. Due to nonspecific early symptoms and the lack of specific guidelines, the optimal timing of surgery remains unclear. CASE REPORT: A 62-year-old female farmer from Hainan Province, China, presented with persistent lower abdominal pain for over 10 days, followed by low back pain and fever (maximum 38.0 °C). She was diagnosed with type 2 diabetes mellitus based on persistent hyperglycemia and an HbA1c level of 14.8%. Emergency CTA revealed a focal pseudoaneurysmal lesion of the abdominal aorta at the L3 level, with periaortic inflammatory changes and suspected contained rupture, but no active contrast extravasation. As the patient was hemodynamically stable, empirical piperacillin/tazobactam therapy was initiated with close monitoring. Blood cultures on hospital day 5 suggested gram-negative bacilli, prompting a switch to imipenem/cilastatin. On day 6, cultures confirmed B. pseudomallei, susceptible to imipenem, ceftazidime, and TMP-SMX. Targeted antimicrobial therapy was continued with addition of TMP-SMX. The patient's fever, pain, and inflammatory markers improved significantly. Follow-up CTA on day 21 showed marked resolution of periaortic inflammation, and blood cultures became negative on day 28. Antimicrobial therapy was switched to ceftazidime on day 30, and open vascular reconstruction was performed on day 38. CONCLUSION: In melioidosis-endemic regions, aortic infection should be considered in diabetic patients with fever and abdominal or back pain. For carefully selected patients with suspected contained rupture, hemodynamic stability, and good response to targeted antimicrobial therapy, delayed elective open reconstruction under strict surveillance and with emergency intervention capability may be a feasible strategy. However, this single case cannot establish the superiority of delayed surgery or define the optimal timing of intervention.

PURPOSE: Among breast cancer (BC) survivors, overweight and obesity increase the risk of recurrence, underscoring the importance of dietary strategies for weight management. The Mediterranean diet (MD) can promote weight loss and reduce lipid levels. Analyzing alterations at the lipid species level can provide more detailed insights into the metabolic benefits associated with the MD. This study aimed to explore lipid remodeling associated with MD adherence in BC survivors through comprehensive lipidomic analysis. METHODS: This exploratory ancillary study was conducted as non-randomized, non-controlled pre-post intervention analysis of serum samples collected before and after an 8-week MD intervention from 12 overweight or obese BC survivors. Fasting paired serum samples (n = 24) were used to profile lipid species using ultra-high-performance liquid chromatography-tandem mass spectrometry in both positive and negative ionization modes. Multivariate and correlation analyses were used to assess overall lipidomic alterations. Participants were further classified into maintainer or improver subgroups based on changes in their Mediterranean diet score (MDS), and subgroup-specific lipidomic responses to the MD intervention were examined. RESULTS: Participants showed significant reductions in body weight, waist circumference, and clinical triglyceride levels, along with increased quantitative insulin sensitivity check index and MDS following the MD intervention. Forty-three putative lipid species were identified, predominantly characterized by reductions in triacylglycerols (TGs) enriched with saturated fatty acids. TG 16:0_18:0_18:0 and TG 16:0_18:1_24:0 exhibited strong negative correlations with MDS and positive correlations with insulin resistance markers. Significant lipid remodeling was observed only in the maintainer group. CONCLUSION: In this exploratory study, adherence to an 8-week MD was associated with changes in body composition, metabolic markers, and the serum lipidomic profile in overweight and obese BC survivors. These findings provide preliminary evidence that MD adherence may be associated with lipidomic and metabolic changes in BC survivors, warranting confirmation in larger, controlled studies. CLINICAL TRIAL REGISTRY: http://clinicaltrials.gov , NCT03581630.

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome is a recently defined clinical entity integrating metabolic risk factors, chronic kidney disease, and cardiovascular disease. Elevated body mass index (BMI) is a major modifiable risk factor for CKM syndrome, yet comprehensive long-term analyses of the high BMI-attributable burden in China remain scarce. METHODS: Using data from the Global Burden of Disease (GBD) 2023 study, we assessed the burden of eight selected CKM-related diseases attributable to high BMI (atrial fibrillation and flutter [AFF], chronic kidney disease due to hypertension [CKD-HTN] or diabetes mellitus type 2 [CKD-T2DM], diabetes mellitus type 2 [T2DM], hypertensive heart disease [HHD], ischemic heart disease [IHD], lower extremity peripheral arterial disease [LEPAD], and stroke) in China from 1990 to 2023. The primary outcomes were absolute deaths and DALYs and their age-standardized rates (ASRs) per 100,000 population. Joinpoint regression and ARIMA models were applied to analyze and project temporal trends in ASRs, age-period-cohort analysis was conducted using age-specific rates, and decomposition analysis quantified the contributions of population growth, population aging, and epidemiological change to changes in absolute deaths and DALYs. RESULTS: From 1990 to 2023, absolute deaths and DALYs for all eight selected diseases relevant to the CKM framework increased. IHD had the highest burden in 2023 (114,980 deaths; 2,923,595 DALYs), whereas AFF showed the greatest relative increase (11.4-fold). Descriptively, men generally had higher point estimates of death and DALY counts, ASMRs, and ASDRs for CKD-T2DM, CKD-HTN, IHD, and HHD, whereas women had higher corresponding estimates for AFF. Joinpoint regression identified sustained increases in AFF, IHD, T2DM, and LEPAD, with several inflection points around 2005. APC analysis showed pronounced age-related gradients and variations in period and cohort rate ratios. Decomposition analysis indicated that population aging was the predominant contributor to increasing mortality for most outcomes, while epidemiological change had heterogeneous effects and partially offset increases in CKD-T2DM and HHD. Model-based projections suggested heterogeneous future trajectories: increasing mortality and DALY rates for AFF, IHD, and LEPAD; increasing DALYs but slightly declining mortality for T2DM; broadly stable or slightly declining rates for stroke, CKD-T2DM, and CKD-HTN; and declining point estimates for HHD, although with substantial long-term uncertainty. CONCLUSION: High BMI-attributable stage 2-4 CKM burden has risen sharply in China and will continue to increase, driven mainly by worsening epidemiological risks. AFF, IHD, and LEPAD show the fastest growth. Men had higher age-standardized mortality and DALY rates for several selected diseases. Early-life obesity prevention and sex-tailored interventions are urgently needed.

Diabetic retinopathy is a potentially blinding complication of diabetes mellitus and the leading cause of irreversible vision loss in the working age population. Diabetic retinopathy has historically been thought of as a microvascular complication of diabetes, but more recent research has shown that retinal neurons and glia are affected prior to clinically detectable vascular alterations. While treatments have been developed to address the vascular lesions of diabetic retinopathy, there are currently no treatments for the early-onset neuro-glial perturbations. Increasing evidence supports inflammation as a critical factor in the development of neuro-glial dysfunction in the diabetic retina. Inflammatory processes are further activated in retinal neurons themselves in response to diabetes. The current review focuses on inflammatory molecular and physiological changes in the diabetic retina. The emerging evidence for a relationship between retinal neurons and glia and the inflammatory cascade is explored.

Diabetes is a chronic condition characterised by hyperglycaemia due to impaired insulin secretion, insulin action, or both. Oxidative stress reduces insulin sensitivity and contributes to complications. Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder of erythrocytes, impairs NADPH production and reduces the ability to counter oxidative stress. Given the involvement of redox imbalance in diabetes pathogenesis, the role of G6PD deficiency in diabetes development and progression remains unclear. Two reviewers independently searched PubMed, Cochrane Library, and Embase to August 10th, 2026, for primary studies on G6PD deficiency and diabetes, resolving discrepancies by discussion. Forty-two studies met inclusion criteria. G6PD deficiency was more prevalent in T2DM patients than in the general population. Diagnostic complications, including artificially reduced HbA1c, were identified. Specific G6PD variants were associated with increased risk and severity of diabetes-associated retinopathy. G6PD deficiency was also linked to increased risk of myocardial infarction, stroke, and arterial stiffness. Consistent evidence indicates a higher risk of complications associated with G6PD deficiency and diabetes, though associations with diabetes onset remain inconsistent. Future research should investigate genetic stratification, oxidative stress biomarkers, and strategies to reduce morbidity.

AIMS: Exocrine pancreatic abnormalities have been reported in type 2 diabetes mellitus (T2DM), but their clinical relevance remains uncertain. We assessed whether T2DM is associated with a clinically meaningful exocrine pancreatic phenotype. METHODS: Adults undergoing endoscopic ultrasound (EUS) for non-pancreatic indications were prospectively enrolled. Patients with known or suspected pancreatic disease were excluded. Non-diabetic controls were frequency-matched to patients with T2DM by sex and age. EUS abnormalities, pancreatic body diameter, elastography, faecal elastase-1 (FE-1), symptoms, GIQLI, PEI-Q and nutritional markers were compared using adjusted models. EUS was performed by endosonographers blinded to diabetes status. RESULTS: We analysed 57 T2DM patients and 53 controls. EUS abnormalities were similar between groups (2.16 ± 1.97 vs 1.77 ± 2.02; p = 0.186), including ≥ 5 abnormalities (15.8% vs 13.2%; p = 0.701). Pancreatic body diameter, mean strain ratio, FE-1, GIQLI, PEI-Q and nutritional markers were comparable. Low FE-1 < 200 µg/g was not more frequent in T2DM (10.9% vs 18.0%). Early satiety and diarrhoea were more frequent in T2DM. CONCLUSIONS: In this selected EUS-referred population without known or suspected pancreatic disease, T2DM was not associated with clinically relevant exocrine dysfunction, pancreatic atrophy or a coherent chronic pancreatitis-like EUS phenotype. These findings support phenotype-based pancreatic function testing in T2DM.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease which requires sustained lifestyle modifications. Psychological and diabetes-related distress may affect treatment adherence. Psychotherapy-based approaches are being incorporated into diabetes care, but their impact on glycemic control and anthropometric outcomes has not been clearly understood. We examined the effects of psychotherapy-based interventions on glycemic control (HbA), body weight and body mass index (BMI) in adults with T2DM across fifty-two studies which were included in the analysis. Psychotherapy-based interventions showed a significant reduction in HbA levels, with greatest effect at 3-month follow-up (MD - 0.53%, 95% CI - 0.80 to -0.25). Among anthropometric outcomes, weight loss was significantly reduced at 12 months (MD -3.58, 95% CI -5.62 to -1.53), whereas BMI showed less consistent effects. Overall, psychotherapy-based interventions resulted in consistent improvements in HbA and longer-term reductions in body weight in adults with T2DM. The earlier improvements in HbA1c may reflect the influence of psychological support leading to changes in dietary and diabetes self-management behaviors, whereas anthropometric changes require sustained behavioral modification.

AIMS: To assess the incidence of microvascular and macrovascular complications and mortality within three years after clinical diagnosis of type 2 diabetes mellitus (T2DM), and to identify associated risk factors. METHODS: In this retrospective population based study, 5773 individuals aged 40-90 years diagnosed with T2DM in Region Halland, Sweden between 2015 and 2020 were included. Data were obtained from a regional healthcare database, and individuals were followed individually from the date of diabetes diagnosis for three years or until death, whichever occurred first. The primary outcome was a composite of microvascular complications, macrovascular complications, and all-cause mortality. Associations between clinical factors and outcomes were analyzed using Cox regression. RESULTS: Within three years, 36% of individuals developed complications and 4% died. Microvascular complications were more common than macrovascular events. In analyses of the composite outcome, impaired kidney function was associated with increased risk (hazard ratio [HR] 2.70, 95% confidence interval [CI] 2.08-3.52), as was poor glycemic control (HR 1.38, CI 1.19-1.59). Higher age increased risk, while female sex was associated with a lower risk. CONCLUSIONS: A substantial proportion of individuals developed complications shortly after clinical diagnosis of T2DM. These findings highlight the importance of early assessment of glycemic control and kidney function for risk stratification and identification of individuals at increased risk of adverse outcomes.

BACKGROUND: To date, no studies have examined the role of insulin resistance (IR) in the relationship between depression and cardiovascular-kidney-metabolic (CKM) syndrome. OBJECTIVES: This study aims to explore the association between CKM and depression, and to determine whether IR mediates this relationship. METHODS: A total of 8584 participants were included in the analysis. CKM was categorized according to the 2023 American Heart Association guidelines. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with a score ≥10 indicating the presence of depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations, and mediation analysis was performed to evaluate the potential mediating effect of IR biomarkers. RESULTS: Of the participants, 675 exhibited clinically significant depressive symptoms. After adjusting for confounders, compared with participants in CKM stage 0, those in CKM stages 1, 2, and advanced CKM exhibited increases in PHQ-9 scores of 0.41, 0.68, and 1.82, respectively (all p < 0.05). Among the core depressive symptoms, fatigue showed the strongest association with advanced CKM (β = 0.45, 95% CI: 0.32-0.57, p < 0.001). Additionally, all IR biomarkers demonstrated significant partial mediation effects (p < 0.05), with the estimated glucose disposal rate (eGDR) showing the largest mediation effect (7.04%). CONCLUSION: Advanced CKM is positively associated with depressive symptoms, and IR partially mediates this relationship. These findings highlight the importance of enhanced mental health screening in patients with advanced CKM and suggest that improving IR may be a potential therapeutic target for future interventions.

BACKGROUND: Cord blood 25-hydroxyvitamin D [25(OH)D] at birth reflects maternal vitamin D availability and maternal-fetal handling. We compared cord 25(OH)D across hypertensive disorders of pregnancy (HDP), severe anaemia, gestational diabetes mellitus (GDM), and healthy controls using ANCOVA to determine whether group differences persisted after accounting for maternal substrate availability. METHODS: This cross-sectional comparative study enrolled 400 primigravida women presenting in active labour at ≥34 weeks gestation: HDP (n = 75), severe anaemia (haemoglobin <7 g/dL; n = 75), GDM (n = 50), and uncomplicated controls (n = 200). The primary ANCOVA adjusted for maternal 25(OH)D and clinical group; a pre-specified sensitivity analysis additionally adjusted for gestational age and birthweight. RESULTS: In the primary ANCOVA, HDP was associated with a cord blood deficit (B = -6.14, p < 0.001) and severe anaemia with a smaller deficit (B = -2.93, p < 0.001); GDM was not significantly different from controls. After additional adjustment for gestational age and birthweight, deficits remained significant for HDP (B = -4.85, p < 0.001) and anaemia (B = -1.95, p = 0.002). No HDP neonate met the pre-specified sufficiency threshold of ≥20 ng/mL (0/75, 0.0%; 95% CI 0.0-4.8%). CONCLUSION: HDP remained associated with substantially lower cord 25(OH)D after adjustment for maternal levels, gestational age, and birthweight. This residual association is compatible with altered maternal-fetal vitamin D handling but, given cross-sectional sampling at delivery and absence of direct placental measurements, does not establish impaired placental transport. Severe anaemia showed a smaller residual deficit; GDM showed no significant deficit.

BACKGROUND: Retropharyngeal abscesses (RPAs) are severe deep neck infections that require rapid intervention to prevent life-threatening complications. This study aimed to evaluate the clinical, laboratory, and radiological risk factors that predict the need for intensive care unit (ICU) admission and surgical drainage in adult patients with RPAs. METHODS: A retrospective review was conducted on patients treated for RPAs at our center between January 2013 and December 2023. Of the 64 initial cases, 57 adults were included in the final analysis after excluding pediatric patients and incomplete records. We analyzed the impact of demographics, diabetes mellitus (DM) status, admission laboratory markers (C-reactive protein [CRP], white blood cell [WBC] count), and radiological abscess size on the necessity for ICU admission and surgical intervention. Additionally, Receiver Operating Characteristic (ROC) curves were generated to assess the predictive value of these variables for ICU admission. RESULTS: The cohort's mean age was 37.7 ± 16.7 years, with 9 patients (15.8%) requiring ICU care. Multivariate logistic regression identified DM (OR = 3.61, 95% CI: 1.31-9.92, p = 0.01), admission CRP level (OR = 1.01, 95% CI: 1.00-1.02, p = 0.03), and maximum abscess diameter (OR = 1.09, 95% CI: 1.02-1.18, p = 0.02) as independent predictors of ICU admission. ROC analysis for CRP yielded an area under the curve (AUC) of 0.87; a 200 mg/L cut-off achieved 100% sensitivity and 80.9% specificity. Maximum abscess diameter demonstrated an AUC of 0.81, with a 30 mm cut-off providing 88.9% sensitivity and 71.4% specificity. None of the evaluated parameters significantly correlated with the need for surgical drainage. CONCLUSION: Comorbid DM, elevated CRP levels, and larger abscess dimensions independently predict the need for intensive care in adults with RPAs. The strong discriminative capacity of admission CRP and radiological abscess size highlights their critical utility in early clinical risk stratification and guiding targeted treatment strategies.

BACKGROUND: Gestational Diabetes Mellitus (GDM) is a growing public health concern in Ethiopia. HbA1c is useful for assessing glycemia but is influenced by physiological changes in pregnancy. To our knowledge, no published trimester-specific HbA1c reference intervals exist for Ethiopian non-diabetic pregnant women. This limits population-specific clinical interpretation. METHODS: A facility-based cross-sectional study was conducted from February to July 2025 among 424 non-diabetic pregnant women across all trimesters. Normality of HbA1c distribution was assessed using the Shapiro-Wilk and Kolmogorov-Smirnov tests; outliers were identified using Tukey's fences method. Reference intervals were determined parametrically (mean ±2SD). Differences across trimesters were tested using one-way ANOVA. Because Levene's test indicated a violation of the homogeneity of variances (p < 0.001) and group sizes were unequal, pairwise comparisons were performed using the Games-Howell post hoc test. A p-value < 0.05 was considered statistically significant. RESULTS: HbA1c showed a normal distribution across all trimesters. Reference intervals were 4.8-5.9% in the first, 4.2-5.8% in the second, and 4.5-5.9% in the third trimester. Mean HbA1c levels differed significantly between trimesters (p < 0.05). Lowest in the second trimester 5.00% (95% CI 4.93-5.07) and highest in the first trimester 5.35% (95% CI: 5.31-5.39). Games-Howell post hoc tests confirmed that all pairwise comparisons were significant (p < 0.05). CONCLUSION: Trimester-specific HbA1c reference intervals were defined for non-diabetic pregnant women, demonstrating measurable physiological variation across gestation. The use of locally derived thresholds could improve the accuracy of GDM screening and support more appropriate clinical interpretation.

This systematic review aims to examine the current literature on the effects of whole-body vibration on hormonal levels in individuals with hormonal disorders. A systematic search was performed on six electronic databases to retrieve studies examining the effects of whole-body vibration on hormonal levels in individuals with hormonal disorders. The retrieved studies were assessed against predetermined eligibility criteria in two stages: title and abstract filtration and full-text filtration. The quality of the studies included was assessed using the physiotherapy evidence based (PEDro) scale and their data were summarized in a data extraction sheet. A pooled statistical analysis was conducted in studies that showed homogeneity. The included studies assessed hormonal level in individuals with hormonal disorders across various pathological conditions including fibromyalgia, multiple sclerosis, obese hypothyroid females, diabetes mellitus, and individuals with renal diseases. The effect of whole-body vibration was statistically significant on thyroid hormones, prolactin, cortisol, and irisin, while other studies showed no effect for whole-body vibration on insulin, gonadal hormones, ghrelin and leptin, adiponectin, parathyroid hormone, and insulin-like growth factor 1 in women with fibromyalgia. The whole-body vibration training may have an action in endocrine system as observed by the alteration of plasma concentration of thyroid hormones, prolactin, cortisol and irisin. It is possible that long-term, repeated mechanical vibration could directly or indirectly affect the levels of other hormones.

BACKGROUND: Smoking and lifestyle‑related diseases increase the risk of cancer incidence and progression, but their impact on castration‑resistant prostate cancer (CRPC) remains unclear. This study examined whether diabetes mellitus (DM), hypertension (HT), and smoking habit (SH) affect the prognosis of CRPC patients treated with enzalutamide (ENZ) or abiraterone plus prednisolone (ABI). METHODS: Using data from the ENABLE study for PCa, an investigator‑initiated, multicenter, randomized controlled trial, patients were retrospectively categorized into two groups based on SH. Subsequently, the impact of the absence or presence of either DM or HT and treatment arm (ENZ or ABI) on survival endpoints was investigated. RESULTS: A total of 178 patients were randomized and treated, of whom 161 had available SH information and were included in the analysis (84 SH- and 77 SH+). No significant differences in survival endpoints were observed between the SH- and SH+ groups. In the SH+ group, prostate cancer-specific survival (PCSS) was significantly worse in the with‑DM/HT group than in the no‑DM/HT group (p = 0.0215). Multivariate Cox analysis confirmed that the presence of DM or HT was an independent predictor of poor PCSS. Furthermore, a significant difference in PCSS between the no‑DM/HT and with‑DM/HT groups was observed in the ENZ arm (p = 0.0201), but not in the ABI arm. CONCLUSIONS: SH does not appear to influence the efficacy of ENZ or ABI therapy for CRPC; however, among SH+ patients, the presence of DM or HT was associated with poorer survival outcomes, particularly in those treated with ENZ.