BACKGROUND:Guidelines suggest that the risk of mortality in diabetic foot disease (DFD) is comparable to that of cancer; however, high-quality evidence is lacking. We aimed to compare the mortality of DFD with that of various cancers based on data from international cohorts. METHODS:We defined DFD according to the IWGDF 2023 guidelines, and cancer was defined based on the ICD-10 codes. We included 527, 1784, and 601 patients with DFD and 1219, 100,643, and 152 patients with cancer from the National Health and Nutrition Examination Survey (NHANES), UK Biobank (UKB), and Chongqing Diabetes Registration (CDR) cohorts, respectively. We compared the risk of mortality between DFD and overall or site-specific cancers in the same cohort. RESULTS:Patients with DFD showed 38%, 45%, and 499% higher risks of mortality than patients with overall cancer in the NHANES, UKB, and CDR. For site-specific cancer, the risk of mortality was significantly higher in DFD than in skin cancer (hazard ratio 10.69, 95% CI: 1.37-2.07 in NHANSE; 3.8, 3.72-448 in UKB), breast cancer (1.35, 1.0-1.83 in NHANSE; 1.95, 1.67-227 in UKB), and prostate cancer (1.4, 1.8-179 in NHANSE; 2.61, 2.35-289 in UKB). The mortality rate of DFD is similar to that of most types of cancer, such as colon cancer, lymphoma, and kidney cancer, and is lower than that of a minority of cancers, including lung, pancreatic, and liver cancers. CONCLUSION:Patients with DFD have a higher risk of mortality than overall cancer, particularly skin, breast, and prostate cancers.
AIMS:Sodium glucose cotransporter 2 inhibitors (SGLT2i) are commonly used glucose lowering agents with established cardiac and kidney benefits. Diabetic ketoacidosis (DKA) is a rare complication associated with their use, which entails significant morbidity and mortality. MATERIALS AND METHODS:This retrospective observational study included patients with diabetes (any) admitted with DKA to a large tertiary hospital. Demographic, clinical and laboratory data were extracted from electronic medical records. Outcomes included DKA severity as determined by nadir pH, duration of stay, need for intensive care (ICU) and inpatient mortality. RESULTS:Baseline SGLT2i use was documented in 27/191 patients (14.1%). SGLT2i users had lower nadir pH (7.08 ± 0.15 vs. 7.15 ± 0.12, p = 0.006) and were more likely to have severe DKA (29.6% vs. 12.2%, p = 0.007). After adjusting for multiple covariates, SGLT2i use remained independently associated with DKA severity. ICU admission and hospitalisation duration did not differ between the groups. Inpatient mortality occurred in 3/27 users and 3/164 non-users, while the composite outcome of mortality and/or ICU admission was similar (74.1% vs. 72.0%, p = 0.819). Findings remained consistent after excluding patients with new-onset diabetes. CONCLUSIONS:Among patients hospitalised with DKA in a large tertiary centre, SGLT2i use was associated with a more severe biochemical presentation, reflected by a lower nadir pH. The observed difference in inpatient mortality was based on few events and should be interpreted cautiously.
BACKGROUND:Conventional BMI-based obesity classification fails to capture the metabolic heterogeneity underlying obesity-related heart failure (HF) risk. We evaluated the 2024 European Association for the Study of Obesity (EASO) framework-which integrates central adiposity with medical, functional, and psychological morbidity-to refine HF risk stratification. METHODS:Among 449,550 UK Biobank participants (median follow-up 15.5 years), we applied three obesity definitions: (1) BMI ≥ 30 kg/m2; (2) the EASO framework, which retains the normal-weight category (BMI 18.5-< 25 kg/m2) and reclassifies individuals with BMI 25-< 30 kg/m2 into 'EASO overweight' (WHtR < 0.5 and/or absence of morbidity) or 'EASO new obesity' (WHtR ≥ 0.5 plus ≥ 1 morbidity), while those with BMI ≥ 30 kg/m2 are classified as BMI obesity regardless of morbidity status; and (3) an extended EASO framework that additionally stratifies individuals with BMI ≥ 30 kg/m2 by morbidity status. Morbidity was defined per the 2024 EASO consensus criteria as the presence of ≥ 1 medical, functional, or psychological conditions associated with excess adiposity. Cox proportional hazard models estimated hazard ratios (HRs) for incident HF. RESULTS:The EASO framework reclassified 15.6% of conventionally overweight individuals as obese, increasing the obesity prevalence from 24.5% to 40.1%. Compared with normal-weight individuals, the EASO overweight group (BMI 25-< 30 kg/m2 without central adiposity or morbidity) exhibited the lowest HF risk (HR 0.84, 95% CI 0.80-0.89), confirming that overweight per se confers no excess risk in the absence of morbidity. By contrast, EASO new obesity (BMI 25-< 30 kg/m2 with central adiposity and ≥ 1 morbidity; HR 1.32, 95% CI 1.25-1.39) demonstrated that morbidity presence-not BMI threshold-drives elevated HF risk within the overweight range. BMI obesity (BMI ≥ 30 kg/m2) yielded the highest summary HR (1.62, 95% CI 1.53-1.71), reflecting its compositional enrichment with high-morbidity individuals rather than superior risk discrimination. In the extended framework, morbidity status produced a consistent vertical upward shift in HF risk across all adiposity categories, establishing phenotypic characterisation beyond anthropometric thresholds as the key determinant of HF vulnerability. CONCLUSIONS:The EASO framework refines HF risk stratification by uncovering morbidity-driven vulnerability within the overweight range that BMI alone obscures. The extended framework further demonstrates that morbidity status-rather than anthropometric thresholds-is a primary modifier of HF risk across all adiposity categories, supporting a shift from purely anthropometric toward phenotype-based obesity classification in cardiovascular risk assessment.
INTRODUCTION:Diabetic foot (DF) disease, including ulcerations, amputations, and infections, represents a major cause of morbidity and mortality in individuals with diabetes mellitus (DM). Despite their substantial clinical, social, and economic burden, robust global epidemiological estimates remain limited due to fragmented evidence and heterogeneous methodologies. This systematic review and meta-analysis aimed to provide reliable pooled estimates of incidence and prevalence of DF disease, to explore geographic and demographic variations, and to assess the types of data sources available for epidemiological research. METHODS:Following PRISMA guidelines (PROSPERO registration CRD42025640944), PubMed, Embase, CINAHL Plus, and Cochrane Library were systematically searched from inception to December 21, 2024, for observational studies in adults (≥ 18 years) with DM reporting epidemiological measures of DF disease. Data extraction and quality appraisal (Joanna Briggs Institute checklists) were independently performed by four reviewers. Random-effects meta-analyses were conducted using generalised linear mixed-effects models to calculate pooled complication-specific prevalence and incidence rates among patients with diabetes. Heterogeneity among study estimates was assessed using Cochran's Q test, I2 statistic, and the between-study variance (τ2). To identify sources of heterogeneity, meta-regression analyses were performed considering study-level covariates (modifiers). RESULTS:Eighty-nine studies were included (18 prospective cohorts, 33 retrospective cohorts, 38 cross-sectional), enrolling between 92 and 29,650,811 participants, with data from Europe (N = 29, 32.6%), Asia (N = 25, 28.1%), Africa (N = 16, 18.0%), America (N = 16, 18.0%), and Oceania (N = 3, 3.4%). Pooled global incidence rates were 10.93 cases/1000 person-years (95% CI, 6.67-17.91) for ulcerations, 3.58 (95% CI, 1.93-6.63) for amputations, and 19.11 (95% CI, 4.81-75.97) for infections. Pooled prevalence estimates were 54.57 cases/1000 persons (95% CI, 37.63-78.52) for active ulcerations, 72.63 (95% CI, 48.21-108.02) for past ulcerations, 14.75 (95% CI, 9.52-22.77) for amputations, and 39.17 (95% CI, 6.81-195.07) for infections. Substantial heterogeneity (I2 > 90%) was observed, with significant modifiers including geographical region, diabetic foot identification method, data source, study setting, age, diabetes duration, and length of follow-up. Rates in America and Africa were generally above the global pooled average, whereas those in Europe, Asia, and Oceania were below. CONCLUSIONS:Globally, DF disease is common and severe, with incidence and prevalence rates underscoring its important public health impact. Heterogeneity across studies highlighted the influence of geography, methodology, and data sources. These findings may support future clinical and pharmacoepidemiological studies that evaluate new interventions and monitor temporal trends using large-scale data.
AIM:The study aims to identify distinct cardiometabolic phenotypes based on multiple metabolic risk indicators, assess their associations with sociodemographic characteristics, and evaluate income-related differences through cardiometabolic risk using decomposition methods to quantify the contribution of observed factors to these disparities. MATERIALS AND METHODS:A cross-sectional analytical study was conducted using National Health and Nutrition Examination Survey (NHANES) 2011-2018 data. Adults aged 20 years and above with complete cardiometabolic biomarker data were included. Six cardiometabolic indicators including waist circumference, systolic blood pressure, fasting plasma glucose, glycated haemoglobin, triglycerides, and high-density lipoprotein cholesterol were used to derive latent phenotypes using latent class analysis. Multinomial logistic regression examined associations between sociodemographic factors and phenotype membership. Oaxaca-Blinder decomposition analysis assessed income-related disparities in the high cardiometabolic risk phenotype. RESULTS:A total of 7733 participants were included in the analysis. A three class model demonstrated optimal fit and identified metabolically healthy (54.9%), hypertension-hyperglycemia (33.1%) and high cardiometabolic risk (11.9%) phenotypes. The high-risk phenotype exhibited elevated probabilities of obesity, dyslipidemia and glycaemic abnormalities. Increasing age, male sex, lower income and lower educational attainment were significantly associated with high risk phenotype membership. Decomposition analysis demonstrated modest income-related disparities, with waist circumference and education contributing the largest explained components. CONCLUSION:Cardiometabolic risk among U.S. adults clusters into three distinct phenotypes associated with sociodemographic and metabolic determinants. These findings highlight the need for integrated strategies targeting early metabolic dysregulation and broader social determinants of health.
AIMS:Depression and long-term HbA1c variability are associated with adverse outcomes in type-2 diabetes (T2D), which may be related to suboptimal self-management practices and health-related quality of life (HRQoL). MATERIALS AND METHODS:In the prospective Hong Kong Diabetes Register (2013-2019), we estimated the independent and joint associations of depression and HbA1c variability with outcomes. Depression was measured using the Patient Health Questionnaire-9 (PHQ-9) with a validated Chinese cut-off score ≥ 7. The HbA1c variability score (HVS) was expressed as the percentage of HbA1c, which varied by 0.5% compared to the preceding value. RESULTS:Amongst 5657 Chinese patients with T2D [58.7% male, age (mean ± SD): 58.47 ± 10.62 years, duration of diabetes: 10.63 ± 8.19 years and time-weighted HbA1c: 7.44% ± 1.04%], 13.3% had depression. After full adjustment, depression was associated with increased risk of cardiovascular disease (CVD) [adjusted hazard ratio (aHR): 1.79 (95% CI: 1.15-2.79); p = 0.010], whereas high HVS (≥ median, 42.9%) was associated with increased risks of chronic kidney disease (CKD) [1.49 (1.21-1.82); p < 0.001] and severe hypoglycaemia (SH) [1.93 (1.22-3.07); p = 0.005]. The depression-high-HVS group had the highest aHR for CKD, which was attenuated from 1.90 (1.41-2.56) to 1.74 (1.25-2.44), and that for all-cause mortality from 2.00 (1.33-3.01) to 1.72 (1.06-2.78) after adjustment for self-management practices and HRQoL. CONCLUSIONS:Depression and high HVS are independently and differentially associated with adverse events, with the depression-high-HVS group having the worst outcomes, which were modulated by self-management and HRQoL, calling for systematic screening of depression and holistic management aimed at avoiding fluctuating glycaemic control in T2D.
AIMS:The social drivers of diabetic foot disease (SDDFD) impact ulcer incidence and outcomes, but how is relatively unknown. We aimed to build a conceptual model positing how three SDDFD-poverty, insurance, and government assistance-influence outcomes for patients with diabetic foot ulcers. MATERIALS AND METHODS:To inform the model, we conducted a scoping review of studies linking poverty, insurance, and/or government assistance with diabetic foot ulcer outcomes using Levac and colleagues' 6-stage framework, the Preferred Reporting Items for Systematic Review and Meta-analysis extension for scoping reviews, and the SPIDER tool. We searched PubMed, CINAHL, and Embase for original research articles set in the United States and published between 1 January 2005 and 7 November 2025. We excluded those published in a language other than English, case reports, abstracts, and studies of other SDDFD. RESULTS:Data from 35 included studies informed our conceptual model, depicting a complex causal pathway between SDDFD and outcomes, often mediated by healthcare system factors and moderated by patients' abilities to adhere to healthcare recommendations. Multidisciplinary teams might ameliorate the risk of amputations associated with poverty, lack of insurance, or qualifying for government assistance. Additionally, the model highlights reinforcing feedback loops, both positive and negative. CONCLUSION:Our model can be used to inform mediation and moderation analyses and help avoid collider-conditioning bias during statistical analyses. It can help identify potential points of intervention within the healthcare system for those working to dampen the negative effects of SDDFD on outcomes.
BACKGROUND AND AIMS:Gestational diabetes (GDM) and preeclampsia (PE) are major complications of pregnancy. The ratio of soluble Fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF) may predict the short-term absence of PE in pregnant women with clinically suspected PE. The aim of this study was to determine the role of placental angiogenic factors in predicting PE risk in women with pregnancies complicated by GDM. MATERIALS AND METHODS:In this prospective observational study, pregnant women were enrolled at the time of screening for GDM. sFlt-1 and PlGF were measured at 24-28, 28-32 and 35-37 weeks of gestation. Univariate and multivariate analysis were used to investigate risk factors for PE. RESULTS:Of 398 women, 213 (53.5%) had GDM and 18 (5%) developed PE (67% with GDM). GDM women developing PE had significantly lower levels of PlGF at 24-28, 28-32 and 35-37 gestational weeks, and higher sFlt1 and sFlt1/PlGF at 28-32 and 35-37 gestational weeks compared with GDM women without PE. On a multivariate analysis, PlGF and sFlt1/PlGF were associated with PE, regardless of other clinical data. A sFlt1/PlGF ratio > 38 at 28-32 gestational weeks identified GDM women at risk of developing PE within the ensuing 4 weeks, with 100% sensitivity and good specificity. CONCLUSION:In women with GDM, the sFlt1/PlGF ratio can identify those at higher risk of PE. TRIAL REGISTRATION:NCT04877119: 2021-04-29.
Type 1 Diabetes (T1D) is an autoimmune disorder marked by the immune-mediated destruction of pancreatic β-cells, resulting in insulin deficiency and dysregulated glucose control. Current therapies-such as insulin replacement and artificial pancreas systems-manage symptoms but fail to restore endogenous β-cell function or halt disease progression. Transplantation strategies, including islet allo- and xenotransplantation, offer potential cures but remain limited by immune rejection, donor scarcity, and the adverse effects of systemic immunosuppression. Within the framework of predictive, preventive, and personalised medicine (3 PM), T1D management requires a paradigm shift towards early detection, targeted prevention, and individualised therapy. Predictive biomarkers and molecular phenotyping can identify high-risk individuals and forecast graft outcomes, while preventive strategies-such as localised immunomodulation, bioenergetic support, and control of systemic inflammation-improve tolerance and graft longevity. Personalised interventions, including patient-specific biomaterials, immunoprotective encapsulation, and regulatory T cell-based or stem-cell-derived β-cell replacement, address immune and metabolic heterogeneity. Recent progress in biomaterials, encapsulation, and 3D bioprinting enables the practical implementation of this 3 PM approach by enhancing oxygenation, vascular integration, and specific scaffold design. Integration of AI-driven analytics, digital health monitoring, and multi-modal diagnostics further supports predictive control of transplant outcomes. This review highlights advances in islet transplantation and regenerative biomaterial engineering as key enablers of the transition from reactive treatment to 3 PM-guided, patient-tailored therapy for T1D.
AIMS:This study aimed to explore the interactions among sclerostin, irisin and leptin, as well as their associations with body composition and bone metabolism in Chinese men with obesity. MATERIALS AND METHODS:This study included 26 men with normal weight and 78 men with obesity. Body composition was measured using dual-emission X-ray absorptiometry. Subcutaneous fat, visceral fat and fat content in the liver and pancreas were determined by magnetic resonance. Serum sclerostin, irisin and leptin were detected using the Elisa assay. RESULTS:Compared with men with normal weight, serum sclerostin, irisin and leptin levels as well as whole-body and spinal bone mineral density were increased, whereas pelvic bone mineral density was not different in men with obesity. Partial analysis showed that in men with obesity, serum sclerostin was positively correlated with bone mineral density but not with body composition; serum irisin was positively correlated with fat mass percent, negatively correlated with muscle mass percent, but not with bone mineral density; serum leptin was positively correlated with fat mass, while negatively associated with muscle mass and bone mineral density. Furthermore, body weight showed beneficial effects on whole-body and spinal bone, whereas central fat distribution exerted adverse effects on pelvic bone. Stepwise linear regression revealed that serum sclerostin and whole-body muscle mass were independent predictors of bone mineral density in the over-all cohort. CONCLUSIONS:Serum sclerostin, irisin and leptin show distinct correlations with body composition and bone mineral density in men with obesity, which may partly reflect the complex effects of obesity on bone metabolism.
AIMS:This study examined changes in body composition and bone mineral density (BMD) over 12 months in people with obesity and type 1 diabetes (T1D) treated with a GLP-1 receptor agonist alone (GLP-1RA) or a dual glucose-dependent insulinotropic polypeptide (GIP/GLP-1RA). MATERIALS AND METHODS:This real-world observational study included 70 people with obesity and T1D treated with GLP-1RA alone or dual GIP/GLP-1RA. Dual-energy X-ray absorptiometry (DEXA) was used to quantify regional and total fat mass, lean mass, bone mineral content (BMC) and BMD at baseline and after 12 months of treatment. Overall changes were quantified, and changes stratified by percentage weight loss using repeated measures analysis. RESULTS:Over 12 months body weight (-6.33%; 95% CI: -7.92, -4.73; p < 0.001), HbA1c (-0.48%; 95% CI: -0.74, -0.22; p < 0.001), total tissue fat (-1.42%; 95% CI: -2.47, -0.36; p = 0.009), fat mass (-5.90%; 95% CI: -10.50, -1.57; p = 0.001), and lean mass (-1.75%; 95% CI: -3.50, -0.48; p = 0.005) decreased, while total BMC and BMD remained unchanged. Total lean mass loss was associated with body weight loss (R2 = 0.36, p < 0.001). CONCLUSIONS:In people with obesity and T1D, 12-month GLP-1RA alone or dual GIP/GLP-1RA therapy resulted in clinically meaningful weight loss, improved glycaemic control, preferential fat mass reduction, modest lean mass loss, and preservation of total BMD. People achieving > 10% weight loss derived the greatest metabolic benefit without compromising bone health, although the loss of lean mass was greater.
BACKGROUND:Diabetic foot ulcers (DFUs) have become an important cause of disability and death in patients with diabetes. Traditional therapies are prone to problems such as recurrence and drug resistance, which result in unsatisfactory healing effects for DFUs. Although antibiotics are not the mainstay of treatment for DFUs, antibiotic resistance poses a critical clinical challenge for DFU patients who require long-term antibiotic therapy. MAIN TEXT:This review summarises the mechanism by which Cold Atmosphere Plasma (CAP) kills bacteria and activates healing ability through the production of reactive oxygen/nitrogen species (RONS). RONS, as the key active species of CAP, exert antibacterial effects in a series of bacterial, cellular, and animal experiments, promote cell migration and proliferation, stimulate angiogenesis, and exert anti-inflammatory effects. However, current high-quality clinical trials are still lacking, leaving substantial room for further clinical exploration of CAP in the treatment of DFUs. Finally, the challenges and prospects of CAP in treating diabetic foot ulcers are summarised. CONCLUSIONS:As a comprehensive and innovative treatment method, the RONS produced by CAP offer a potential approach for treating DFUs and serve as a tool for promoting their healing. However, more clinical studies are needed for further verification.
AIMS:Pancreatic cancer remains one of the most lethal malignancies due to late diagnosis and limited opportunities for prevention. Cardiovascular-kidney-metabolic (CKM) syndrome reflects the cumulative burden of metabolic, renal, and cardiovascular dysfunction, but its association with pancreatic cancer risk has not been well established. We investigated this relationship in a large prospective cohort from the UK Biobank. MATERIALS AND METHODS:Participants without pancreatic cancer at baseline (2006-2010) were followed through national cancer and mortality registries until 31 December 2022. CKM syndrome was categorised into five stages (0-4) according to American Heart Association criteria. Incident pancreatic cancer was identified using ICD-9 and ICD-10 codes. Fine-Gray subdistribution hazard models accounting for death were used to estimate subdistribution hazard ratios (SHRs) and 95% confidence intervals (CIs), with prespecified subgroup analyses performed. RESULTS:Among 326,148 participants, 1234 incident pancreatic cancer cases were identified over a mean follow-up of 13.5 years (SD 2.0). Incidence rates increased progressively from 9.0 to 48.6 per 100,000 person-years across CKM stages. Compared with CKM stage 0, multivariable-adjusted SHRs for pancreatic cancer were 1.97 (95% CI 1.28-3.02) for stage 1, 2.02 (1.42-2.87) for stage 2, and 2.08 (1.42-3.04) for stages 3-4 (p for trend < 0.001). Associations were generally consistent across subgroup analyses according to age, sex, smoking status, and alcohol consumption, without statistically significant interaction effects. CONCLUSIONS:Advanced CKM syndrome was independently associated with higher pancreatic cancer risk, supporting its potential role in risk stratification and early detection strategies.
AIMS:Diabetic foot ulcers (DFU) continue to occur despite established prevention guidelines, yet consumer perspectives, particularly from socioeconomically disadvantaged and culturally and linguistically diverse (CALD) communities, have been underrepresented in shaping prevention. To address this gap, we aimed to co-design a consumer-derived prevention research agenda by identifying barriers and enablers, establishing research priorities, prioritising implementation strategies, and defining meaningful outcome measures. METHODS:Four sequential workshops were conducted with 11 consumers with a history of DFU in South East Queensland, including Aboriginal and Pacific Islander participants (n = 4) and those from areas of socioeconomic disadvantage (n = 8). Rapid qualitative analysis informed iterative refinement across workshops, with priorities, implementation strategies, and outcome measures ranked by participants. RESULTS:Participants identified barriers across clinical, self-care, psychosocial, social, and financial domains, including feeling unsupported when trying to prevent DFU, the cognitive burden of constant vigilance, conflicting guidance, and the financial and travel costs of care. The highest-ranked research priorities were better ways to predict problems before they happen (median 2, IQR 1-4.5), formal education support (median 4, IQR 3-9), and tools to support regular foot checks (median 5, IQR 3-6). Across all three priorities, consumers consistently selected technology enabled implementation strategies, including wearable sensors, AI powered personalised learning, and smart interventions. Participants defined prevention success through quality of life, function, and confidence outcome measures rather than clinical endpoints alone. CONCLUSIONS:For socioeconomically disadvantaged and CALD populations, effective DFU prevention must be technology enabled, personalised, and developed in partnership with the consumer.
Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal because most patients are diagnosed after curative treatment is no longer feasible. Diabetes mellitus and PDAC have a bidirectional relationship: long-standing type 2 diabetes mellitus (T2DM) modestly increases background cancer risk, whereas new-onset diabetes (NOD), particularly after 50 years of age, may represent a paraneoplastic manifestation of occult PDAC. Population-based data suggest that approximately 0.6%-0.85% of older adults with NOD are diagnosed with PDAC within 3 years. This absolute risk is too low to justify universal imaging, but high enough to support phenotype-based triage. This review clarifies the distinction among T2DM, PDAC-associated diabetes, type 3c diabetes mellitus related to non-malignant exocrine pancreatic disease, and post-pancreatectomy dysglycemia. We also summarise epidemiological and biological evidence connecting dysglycemia with PDAC, including insulin resistance, hyperinsulinemia, impaired insulin secretion, cachexia-related metabolic change, and exocrine-endocrine crosstalk. Particular emphasis is placed on selective diagnostic escalation. Age at diabetes onset, unintended weight loss, HbA1c or glucose trajectory, insulin resistance indices, biomarkers, and risk-enrichment models, including the Enriching New-Onset Diabetes for Pancreatic Cancer (END-PAC) model, should be interpreted together rather than in isolation. Pancreas-protocol computed tomography remains the first-line diagnostic study when PDAC is suspected, while magnetic resonance imaging and endoscopic ultrasonography play complementary roles. We further discuss implications for pancreatic surgery, perioperative metabolic care, postoperative dysglycemia, and lessons from high-risk surveillance cohorts. A diabetes-centred framework may improve early recognition without promoting indiscriminate screening.
BACKGROUND AND AIMS:People with type 1 diabetes mellitus (T1D) are at increased risk of disordered eating behaviours (DEBs), partly due to aspects of diabetes management. The aim of this study was to estimate the prevalence of DEBs in a group of adults with T1D in Spain and to examine their association with sociodemographic, clinical, and lifestyle-related factors. METHODS:A nationwide cross-sectional study was conducted as part of the D1ANAS project, involving 451 people aged ≥ 16 years with T1D living in Spain. DEBs were assessed using the validated Spanish version of the Diabetes Eating Problems Survey-Revised (DEPS-R), with scores ≥ 20 indicating a positive screening. Sociodemographic, clinical, and lifestyle variables were collected using a self-administered online questionnaire. Multivariate linear regression analyses were performed to identify factors independently associated with the total DEPS-R score. RESULTS:The mean DEPS-R score was 16.8 (SD 12.1), and 31.7% of participants screened positive for DEBs, with higher prevalence in women than men (35.4% vs. 14.8%, p < 0.001) 36.6% of participants reported insulin restriction behaviours, with no significant differences between sexes. In the adjusted models, female sex (β = 3.23, 95% CI = 0.65-5.82), higher HbA1c percentage (β = 2.12, 95% CI = 1.32-2.93), and higher zBMI (β = 3.44, 95% CI = 2.44-4.44) were independently associated with higher DEPS-R scores, as were poorer perceived health (β = 5.11, 95% CI = 2.25-7.96), poorer diet quality (β = 13.42, 95% CI = 7.23-19.61) and poor sleep perception (β = 3.43, 95% CI = 1.46-5.39). The model explained 29.6% of the variance in DEPS-R scores. CONCLUSION:DEBs affect about one-third of the participants with T1D and are associated with poorer metabolic control, higher BMI, and adverse lifestyle and psychosocial factors, highlighting the need for diabetes-specific screening and multidisciplinary management.
OBJECTIVE:To evaluate the atrial fibrillation (AF) risk of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), glucagonlike peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in patients with Type 2 Diabetes Mellitus (T2DM) with network meta-analysis. METHODS:Systematic literature searches were conducted of MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Clinical Trials.gov covering inception till January 31, 2026. Randomized control trials (RCTs) and cohort studies comparing SGLT-2i, GLP-1RA and DPP-4i in diabetes were selected. We performed a network meta-analysis to compare the three drugs indirectly. Results were reported as risk ration (RR) with corresponding 95% confidence interval (CI). RESULTS:4 RCTs and 21 cohort studies involving 2,171,267 patients were included. Compared with GLP-1RA [RR with 95% CI: 0.86(0.79, 0.95), RR with 95% CI: 0.87(0.78, 0.97)] and DPP-4i[RR with 95% CI: 0.80(0.74, 0.87), RR with 95% CI: 0.81(0.74, 0.88)], SGLT-2i significantly reduced the risk of AF and new-onset AF. While there were no significant difference in the risk of AF recurrence among SGLT-2i, GLP-1RA, and DPP-4i[RR with 95% CI: 0.87(0.68, 1.12), RR with 95% CI: 0.80(0.61, 1.05), RR with 95% CI: 0.92(0.63, 1.33)]. There were also no significant difference in the risk of AF and new-onset AF between GLP-1RA and DPP-4i[RR with 95% CI: 0.93(0.84, 1.03), RR with 95% CI: 0.93(0.83, 1.04)]. CONCLUSIONS:The management of T2DM involves the prevention of subsequent cardiovascular complications. The results of this network meta-analysis indicate that SGLT2i is associated with a lower risk of AF in T2DM patients compared to GLP-1RA and DPP-4i. Sensitivity analysis further confirms that SGLT-2i significantly reduces the risk of AF recurrence statistically. These finding suggests that SGLT-2i should be considered as a preferred antidiabetic regimen for patients with T2DM at high risk of AF.
Metabolic disorders such as obesity, type 2 diabetes mellitus, and fatty liver disease are associated with a disruption in the coordinated regulation of nutrient sensing, energy metabolism, and cellular homoeostasis. Increasing evidence indicates that sirtuins, a family of NAD+-dependent enzymes, play a central role in integrating metabolic and stress-responsive pathways. By coupling the cellular redox state to transcriptional and post-translational regulation, sirtuins coordinate key processes such as glucose and lipid metabolism, mitochondrial function, and inflammatory signalling. Sirtuins are functionally specialised according to their subcellular localisation. Nuclear sirtuins (SIRT1, SIRT6, and SIRT7) regulate transcriptional programs controlling metabolism and inflammation, whereas mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5) directly modulate metabolic enzyme activity and redox homoeostasis. SIRT2 links cytosolic metabolic signalling to cytoskeletal dynamics and cell cycle regulation. Importantly, the activity of all sirtuins is tightly dependent on NAD+ availability, positioning NAD+ metabolism as a central regulator of the sirtuin network. In this review, we provide a systems-level perspective on sirtuin biology, highlighting how NAD+ metabolism, subcellular compartmentalisation, and specific functions converge to form an integrated regulatory network governing metabolic homoeostasis. We further discuss how disruption of this network contributes to the pathogenesis of metabolic disorders through impaired metabolic flexibility, mitochondrial dysfunction, and chronic inflammation. Overall, this network-based framework provides a unified view of sirtuin function in metabolic regulation and helps to explain the complexity and tissue-specific heterogeneity of metabolic diseases.
Type 2 diabetes mellitus and peripheral artery disease are pathophysiologically interlinked through shared mechanisms such as chronic inflammation and endothelial dysfunction, highlighting the imperative to identify common biomarkers for enhancing early detection and risk stratification. A review of PubMed through December 2025 was performed, culminating in the inclusion of 55 original studies. The synthesis revealed significant dysregulation of inflammatory markers including IL-6 and ICAM-1, endothelial and oxidative stress mediators such as TET3 and the PRDX family, along with coagulation markers such as von Willebrand factor and fibrinogen, all correlating with disease severity in comorbid patients. Multi-marker panels, exemplified by the HART PAD score and combined neutrophil-to-HDL ratio with systemic inflammation response index, demonstrated superior predictive accuracy compared to individual biomarkers. Subsequent investigations should prioritise prospective validation and clinical standardisation of these candidate markers. This scoping review offers a novel structured integration of biomarkers across fluid, cellular and functional domains, advocating for an integrated multi-marker strategy to facilitate personalised management in this high-risk population.
AIMS:To study the associations of dietary intake of A and E vitamins, as well as plasma retinols, carotenoids, and tocopherols in relation to development of islet autoimmunity and progression to T1D. MATERIALS AND METHODS:The Environmental Determinants of Diabetes in the Young (TEDDY) Study followed 7659 newborns with genetic susceptibility to T1D for 6 years in the USA, Finland, Germany, and Sweden. Dietary vitamin intake was assessed repeatedly with 3-day food-records in full cohort at ages 6 months to 6 years. Plasma retinols, carotenoids, and tocopherols were analysed in a nested case-control setting with 359 children with islet autoimmunity and 1033 matched controls. RESULTS:In the full cohort analyses, dietary intake of retinol, β-carotene, and vitamin E was not associated with the risk of islet autoimmunity or progression to T1D. Further, none of the plasma retinol, carotenoid, and tocopherol biomarkers were associated with islet autoimmunity or T1D in the full nested case-control analyses. We observed effect modification by country, breastfeeding, sex, and follow-up time for both intake and biomarkers of vitamins on the risk of islet autoimmunity or T1D, and some subgroup associations. Finally, a plasma carotenoid metabolite (likely zeinoxanthin) (OR 0.61, 95% CI 0.39, 0.95, p = 0.03) and γ-carotene at 6 months (OR 0.65, 95% CI 0.45, 0.94, p = 0.02) were inversely associated with the odds of developing GADA-first. CONCLUSIONS:Retinol, carotenoids and tocopherols were not consistently associated with islet autoimmunity. This study adds to the understanding of factors and their interactions related to T1D development.
