Background The Coronary artery calcium (CAC) score is a validated imaging biomarker that is used in clinical practice to improve cardiovascular risk stratification in patients with type 2 diabetes (T2DM). However, residual risk remains, particularly in patients with moderate CAC. Diabetic retinopathy (DR), a microvascular complication of diabetes, may reflect systemic vascular vulnerability and provide additional prognostic information. Methods This observational cohort study was conducted as part of the primary prevention ACCoDiab study. Four hundred and twenty-four patients with T2DM and no prior history of cardiovascular events underwent CAC scoring and clinical assessment, including screening for DR. The study population comprised 175 females and 249 males, with an average age of 60.9 years. Patients were monitored for seven years for cardiovascular events, including nonfatal myocardial infarction, ischemic stroke, hospitalization for heart failure, revascularization of the limbs due to peripheral artery disease and cardiovascular death. Cox regression, Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and net reclassification improvement (NRI) were employed to evaluate the prognostic value of DR alongside CAC score with the aim of developing a simple cardiovascular risk score. Results Fifty patients (11.8%) experienced cardiovascular events. DR was significantly more prevalent among those who experienced events (58% vs. 25%, p < 0.001). Both CAC score and DR were independently associated with cardiovascular events. Combining the CAC and DR models significantly improved the prediction of events over the CAC model alone (AUC 75.3 vs. 67.8, p = 0.011), with even further improvement when adjusted for traditional risk factors (AUC 78.2, vs 71.3 p = 0.014 vs. the CAC model alone). The presence of DR reclassified a significant proportion of patients into higher risk categories, particularly among those with moderate CAC scores. Conclusion The combination of DR and CAC score significantly enhances cardiovascular risk stratification in patients living with T2DM, even after adjustment for traditional risk factors. Trial registration NCT03920683
The coronary artery calcium (CAC) score is a validated imaging biomarker enhancing cardiovascular risk stratification in patients with type 2 diabetes mellitus (T2DM). However, residual risk persists, particularly among patients with moderate CAC scores. Diabetic retinopathy (DR), a microvascular complication of diabetes, may reflect systemic vascular vulnerability and provide additional prognostic information. This observational cohort study was conducted as part of the primary prevention ACCoDiab study. 424 patients with T2DM (175 females and 249 males, with a mean age of 61 years) and no history of cardiovascular events underwent CAC scoring and clinical assessments, including DR screening. Patients were monitored for seven years or until the first cardiovascular events, including nonfatal myocardial infarction, ischemic stroke, hospitalization for heart failure, peripheral artery disease revascularization, and cardiovascular death. Cox regression, Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, and net reclassification improvement (NRI) were used to evaluate the added prognostic value of DR to CAC scoring and to develop a simple integrated cardiovascular risk score. Fifty patients (11.8
La neuropathie diabétique périphérique est une complication de microangiopathie qui partage une physiopathologie commune avec la rétinopathie et la néphropathie. L’hyperglycémie chronique en est le facteur causal principal, mais d’autres altérations métaboliques, comme la dyslipidémie et l’insulinorésistance, participent aux lésions nerveuses. Celles-ci consistent en une altération des cellules de soutien (cellules de Schwann), une démyélinisation ou une réduction de la transmission axonale et de la disponibilité en neurotrophines pouvant conduire jusqu’à la mort neuronale. Hyperglycémie chronique, inflammation, lipotoxicité, défaillance énergétique par dysfonction mitochondriale se cumulent à des degrés divers pour induire ces lésions qui ne corrèlent pas avec l’intensité des symptômes ressentis et exprimés par les patients. Car la douleur, en partie expliquée par une hyperexcitabilité neuronale, est également amplifiée par le cerveau, suggérant que des thérapeutiques centrales pourraient également réduire les symptômes douloureux. Comme pour toute complication, la neuropathie diabétique peut être prévenue par l’équilibration du diabète.
AIMS:Once-weekly (OW) insulins represent a promising strategy to reduce injection burden and improve adherence in type 2 diabetes management. This meta-analysis aimed to quantify pooled effect sizes for key biological and clinical outcomes, integrating new findings from the five large trials published in 2025. MATERIALS AND METHODS:We systematically searched PubMed, WoS, ClinicalTrials.gov and EU Clinical Trials databases up to June 2025 for randomized controlled trials (RCTs) evaluating OW insulins in type 2 diabetes. Primary outcomes included efficacy (HbA1c, fasting plasma glucose (FPG), time-in-range (TIR), time-above-range) and safety outcomes (body weight, hypoglycaemia, time-below-range). Data were analysed using both frequentist and Bayesian approaches. RESULTS:Among 435 screened records, 16 RCTs were included. OW insulins achieved a greater reduction in HbA1c compared to once-daily insulin or semaglutide (pooled mean difference: -0.12%, 95% CI: -0.19 to -0.04, p = 0.007). TIR was significantly longer in the OW insulin group (+2.41% of total time, 95% CI: 1.13 to 3.69, p = 0.002), while FPG changes were comparable (-3.37 mg/dL, 95% CI: -7.95 to 1.21 mg/dL, p = 0.14). Body weight changes were generally similar, but excluding trials using IcoSema revealed a modest weight gain (+0.33 kg, 95% CI: 0.04 to 0.62, p = 0.030). The incidence of clinically significant or severe hypoglycaemia did not differ between groups (pooled incidence rate ratio: 1.04, 95% CI: 0.79 to 1.28, p = 0.75). Meta-regression confirmed consistent effect sizes across OW insulin types, treatment durations and prior insulin regimens. CONCLUSIONS:OW insulins modestly improve glycaemic control without increasing hypoglycaemia risk, though slight weight gain may occur.
BACKGROUND:We studied the safety and effectiveness of glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2is) in liver transplant recipients with diabetes. METHODS:This retrospective single-center study included 41 patients treated with GLP1-RAs and/or SGLT2is after liver transplantation (LT) who were compared to a control group receiving antidiabetic treatment excluding GLP1-RAs and/ SGLT2is. RESULTS:The treatment group showed no serious adverse events, with 15.0% experiencing moderate side effects, primarily gastrointestinal disorders. The HbA1c target concentration was achieved in 90.0% (n=36) of patients in the GLP1-RA and/or SGLT2i group versus 74.0% (n = 42) in the control-group (p = 0.16). The fasting glycaemia target was reached by a higher proportion of patients in the GLP1-RA and/or SGLT2i group than in the control-group: 80.0% versus 55.0%, p = 0.033. Insulin withdrawal was greater in the group of patients receiving GLP1-RAs and/or SGLT2is treatment, in particular for those with post-transplant diabetes (80.0% vs. 0%, p < 0.01). The median time of follow-up was 11.0 months (IQR: 6-13). CONCLUSIONS:Our results suggest the safety of GLP1-RAs and SGLT2is treatment, with the remarkable benefit of insulin withdrawal for a subgroup of patients with new-onset diabetes. However, larger prospective studies are needed to assess the long-term impact on cardiovascular events, obesity, liver steatosis, and mortality.
Abstract Background Sphingosine 1-phosphate (S1P) is a key mediator of lipid signaling with strong immunomodulatory and anti-inflammatory effects. Circulating S1P levels including S1P in high-density lipoproteins (HDL) were demonstrated to be inversely associated with cardiovascular diseases (CVD). However, no studies are available regarding a potential implication of S1P on the risk of CVD in type 2 diabetes (T2D). The objective of this study is to determine if the increased CVD risk in T2D may involve an alteration of circulating S1P species as well as their precursors. Methods A total of 168 and 31 patients with T2D (154 men and 45 women) with available Coronary artery calcification (CAC) score from the DIACART and CERABIAB cohorts, respectively, were included in the study. Quantification of S1P species and their precursors was carried out by LC–MS/MS in plasma and isolated HDL. CAC score was modeled as a binary variable (0/1 below or equal/above 100) using CAC < 100 for reference. S1P species or precursors were modeled as binary variables dichotomized at the median (0/1: below or equal/above the median). The relationships between S1P species and CAC score modeled as a binary variable (below or equal/above 100) was evaluated by linear regression analyses. In vitro experiments were conducted to evaluate the contribution of HDL-S1P content on anti-inflammatory properties of HDL particles. Results Multivariate analysis revealed that plasma S1P levels, especially d18:1-S1P, and sphingosine in HDL were inversely associated with the high risk of CVD (CAC > 100) in patients with T2D. Clustering of HDL according to their concentration in S1P species and their precursors revealed that S1P-impoverished HDL is a major feature of patients with a CAC > 100. In vitro analysis of monocyte adhesion and inflammation in human umbilical vein endothelial cells as well as inflammatory phenotype of human macrophages demonstrated that low HDL-S1P exhibited impaired anti-inflammatory properties in comparison to high HDL-S1P. Conclusion This study unraveled that circulating S1P and their precursors are biomarkers of coronary atherosclerosis in T2D, which may underlie the lower abundance of S1P and anti-inflammatory activities of HDL. Trial registration ClinicalTrials.gov number, NCT02431234. Graphical abstract
Studies have demonstrated that both lower limb arterial calcification and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to the development of peripheral artery disease. However, the potential relationship between MASLD biomarkers and progression of lower limb arterial calcification in individuals with type 2 diabetes (T2D) remains unclear. This study aimed to investigate whether the biomarkers of MASLD included in the FibroMax® panels are associated with the progression of lower limb arterial calcification in patients with T2D. The lower limb arterial calcification score (LLACS) was evaluated through computed tomography at baseline and after an average follow-up of 31.2 ± 3.7 months in a cohort of 150 patients with T2D. We also measured the serum biomarkers included in the FibroMax® panels (SteatoTest®, FibroTest®, NashTest®, ActiTest®). The predictive ability of these biomarkers of MASLD on LLACS progression was assessed through univariate and multivariate linear regression models, principal component regression analysis, as well as machine learning algorithms. During the follow-up period, LLACS increased in 127 (85
IntroductionDiabetic foot ulcers (DFUs) are a major complication of diabetes, leading to high morbidity, mortality, and healthcare costs. Current DFU risk stratification relies on clinical examination, which can be subjective. Electrochemical Skin Conductance (ESC), measured via Sudoscan, offers an objective assessment of small fiber dysfunction. This study evaluates the association between ESC and DFU risk stratification.MethodsA retrospective analysis of 2,157 diabetic patients from four tertiary centers in France was conducted. DFU risk was classified using the 2016 International Working Group on Diabetic Foot (IWGDF) grading system. ESC measurements were analyzed alongside age, sex, diabetes type, and monofilament test results. Regression and ROC analyses assessed predictive performance.ResultsESC values correlated with DFU grades (p<0.001), with lower foot ESC (FESC) in higher-risk patients. ROC analysis showed strong predictive value for severe DFUs (AUC = 0.82 for grade 3) but limited performance for early stages. Notably, ESC identified at-risk patients within grade 0, undetected by standard classification.DiscussionESC provides a reproducible, operator-independent tool for DFU risk assessment, improving early detection beyond monofilament testing. These findings support its potential role in DFU prevention, reducing amputations and enhancing patient outcomes. Further studies are needed to validate its prognostic value and integration into clinical care.