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Aim: New tools are required to better assess cardiovascular risk in individuals with type 2 diabetes mellitus (T2DM). Plasma ceramides emerge as promising candidates, given their substantial influence on the pathogenesis of both T2DM and atherosclerosis. The current study aimed to investigate whether plasma ceramides in patients with T2DM are a predictive factor for carotid intima-media thickness (CIMT), a well-established noninvasive marker for atherosclerosis that predicts adverse cardiovascular outcomes., Methods: A lipidomic analysis was carried out on the circulating ceramides of a large cohort consisting of 246 patients with T2DM who underwent a high-resolution real-time B ultrasonography to measure CIMT., Results: Both plasma 16:0 ceramide and the 16:0/24:0 ceramide ratio were positively associated with CIMT, even after adjustment for traditional cardiovascular risk factors [standardized β ± standard error: 0.168 ± 0.072 (P = 0.020) and 0.180 ± 0.068 (P = 0.009), respectively]. Similar independent associations were found with respect to the prediction of CIMT ≥ 0.80 mm [β = 8.07 ± 3.90 (P = 0.038) and 16.5 ± 7.0 (P = 0.019), respectively]. The goodness-of-fit for multivariate models in predicting CIMT was 5.7 and 7.6 times higher when plasma 16:0 ceramide or the 16:0/24:0 ceramide ratio were included in combination with traditional cardiovascular risk factors (P = 0.020 and 0.015, respectively). This reached a 3.1 and 10.0-fold increase regarding the ability to predict CIMT ≥ 0.80 mm (P = 0.039 and 0.008, respectively)., Conclusions: Our findings suggest that 16:0 ceramide and the 16:0/24:0 ceramide ratio may serve as plasma biomarkers to improve cardiovascular risk assessment in individuals with T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background: There is growing evidence that ceramides play a significant role in the onset and progression of non-alcoholic fatty liver disease (NAFLD), a highly prevalent condition in patients with type 2 diabetes associated with hepatic and cardiovascular events. However, the relationship between plasma ceramide levels and NAFLD severity in type 2 diabetes remains unclear. The main purpose of the present study was to investigate whether circulating levels of ceramides in patients with type 2 diabetes are associated with liver steatosis assessed by the highly accurate magnetic resonance imaging proton density fat fraction (MRI-PDFF). The secondary objective was to assess the relationship between plasma ceramides and noninvasive scores of liver fibrosis., Methods: In this cross-sectional single-center study, plasma concentrations of 7 ceramides were measured by liquid chromatography-mass spectrometry in 255 patients with type 2 diabetes (GEPSAD cohort). Liver fat content was assessed by MRI-PDFF, and noninvasive scores of liver fibrosis (i.e. Fibrosis-4 index, NAFLD Fibrosis Score, FibroTest® and Fibrotic NASH Index) were calculated. A validation cohort of 80 patients with type 2 diabetes was also studied (LIRA-NAFLD cohort)., Results: Liver steatosis, defined as a liver fat content > 5.56%, was found in 62.4 and 82.5% of individuals with type 2 diabetes in the GEPSAD and LIRA-NAFLD cohorts, respectively. In GEPSAD, MRI-PDFF-measured liver fat content was positively associated with plasma levels of total ceramides (r = 0.232, p = 0.0002), and 18:0, 20:0, 22:0 and 24:0 ceramides in univariate analysis (p ≤ 0.0003 for all). In multivariate analysis, liver fat content remained significantly associated with total ceramides (p = 0.001), 18:0 (p = 0.006), 22:0 (p = 0.0009) and 24:0 ceramides (p = 0.0001) in GEPSAD, independently of age, diabetes duration, body mass index and dyslipidemia. Overall, similar relationship between plasma ceramides and liver fat content was observed in the LIRA-NAFLD validation cohort. No significant association was found between plasma ceramides and noninvasive scores of fibrosis after adjustment for age in both cohorts., Conclusions: Plasma ceramide levels are associated with liver steatosis in patients with type 2 diabetes, independently of traditional risk factors for NAFLD. The independent association between plasma ceramides and liver steatosis adds new insights regarding the relationship between ceramides and NAFLD in type 2 diabetes., (© 2023. The Author(s).)

Nonalcoholic fatty liver disease (NAFLD) encompasses simple liver steatosis, nonalcoholic steatohepatitis (NASH), and liver fibrosis that can progress to cirrhosis. NAFLD has become the principal cause of chronic liver disease in many parts of the world. Lipidomic studies, by allowing to determine concentrations of lipid classes and fatty acid composition of different lipid species, have been of great interest to help understand NAFLD pathophysiology and potentially identify novel biomarkers for diagnosis and prognosis. Indeed, lipidomic data give information on qualitative lipid abnormalities associated with NAFLD. The aim of our article was to create a comprehensive and more synthetic review of main results from lipidomic studies in NAFLD. Literature was searched for all human lipidomic studies evaluating plasma samples of individuals with NAFLD. Results were regrouped by the degree of liver damage, either simple steatosis, NASH or liver fibrosis, and presented by lipid categories. Overall, we summarized the main lipidomic abnormalities associated with NAFLD as follows: modification of free fatty acid distribution, increase in ceramides, reduced phosphatidylcholine / phosphatidylethanolamine ratio, and increase in eicosanoids. These lipid abnormalities are likely to promote NASH and liver fibrosis by inducing mitochondrial dysfunction, apoptosis, inflammation, oxidation, and endoplasmic reticulum stress. Although these lipidomic abnormalities are consistently reported in many studies, further research is needed to clarify whether they may be predictive for liver steatosis, NASH or liver fibrosis., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Hypertriglyceridemia (HTG) is known as the third most common cause of acute pancreatitis (AP)., Objective: To study the prevalence and outcomes of HTG-AP as well as the quality of the follow-up post HTG-AP hospitalization in Canada., Methods: This retrospective multicenter study was performed in patients admitted with AP (ICD 10 code K85) in quaternary care hospitals between 2012 and 2018. For every case of HTG-AP (TG ≥ 5.6 mmol/L on admission), two controls of biliary-AP were selected and matched for sex and age at the time of admission., Results: Out of 1490 admitted AP patients, 40 (3%) had HTG-AP. The average TG concentration was higher in patients admitted to the ICU compared to those who were not (27.34 mmol/L vs 13.02 mmol/L). Compared to biliary-AP group, the HTG-AP patients had more frequent severe Balthazar grade (45% vs 25%) with longer duration of hospitalisation (nine versus five days) and more frequent ICU admission (38% vs 8%). Furthermore, only 35% of HTG-AP patients were referred to specialized clinics and 42.5% were left with no follow-up. Only 17% of newly discovered HTG-AP patients were started on fibrate at discharge., Conclusion: In comparison to biliary-AP, HTG-AP patients had a worse clinical course of pancreatitis. Furthermore, the quality of the follow-up post HTG-AP hospitalization was suboptimal. This could be explained by of the lack of knowledge of health care providers concerning the proper diagnosis and management of chylomicronemia syndromes, leading to this condition to be frequently missed or underdiagnosed., (Copyright © 2022. Published by Elsevier Inc.)

Background: Familial hypercholesterolemia (FH) is a monogenic disease characterized by a high concentration of low-density lipoprotein cholesterol. This population is considered to be at high cardiovascular risk; however, disease evolution remains heterogeneous among individuals. The coronary artery calcium (CAC) score is currently the best predictor of incidental major cardiovascular events in primary prevention in the general population. Few studies have described the CAC score in FH populations., Methods: The objective of our study was to determine the predictors of the CAC score in FH patients. We retrospectively studied FH patients followed at the Montreal Clinical Research Institute (IRCM) Lipid Clinic who had a cardiac scan for CAC score, using the Agatston method, between 2013 and 2019., Results: Final analysis included 62 FH patients. Mean age was 48 ± 14 years old, and 48% were men. Overall, 25 patients had a CAC score of 0 (40%), and 37 patients had a nonzero CAC score (60%). Sex, age, Montreal-FH-SCORE (MFHS), waist circumference, and statin exposure in years were significant predictors ( P ≤ 0,05) of a nonzero CAC score in a univariate model. MFHS was the only factor that remained significant in a multivariate model (odds ratio 1.34, 95% confidence interval 1.11-1.61, P  = 0.002)., Conclusions: In conclusion, we found that MFHS, which includes traditional cardiovascular risk factors, was a predictor of a nonzero CAC score in FH patients. This finding suggests that MFHS may play a role in determining the cardiovascular risk and therefore the intensity of treatment in FH patients., (© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Objective: Nontraumatic osteonecrosis (ON) is a well-recognized complication causing disability and affecting quality of life in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify the risk factors for ON, and to identify the minimal investigation(s) needed to optimally monitor the risk of ON in patients with SLE., Methods: A systematic review was conducted using MEDLINE and EMBASE. These databases were searched up to January 2016 using the Medical Subject Heading (MeSH) terms "Osteonecrosis," "Systemic lupus erythematosus," and synonymous text words. Randomized controlled trials, case control, cohort, and cross-sectional studies were included. Risk factors for ON in patients with SLE were compiled. The quality of each study was assessed using the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of each risk factor was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method., Results: Of the 545 references yielded, 50 met inclusion criteria. Corticosteroid (CS) use may be strongly associated with ON in patients with SLE. Other clinical variables were moderately associated, including hypertension, serositis, renal disease, vasculitis, arthritis, and central nervous system disease. However, the evidence was low to very low in quality., Conclusion: Based on the best evidence available, CS use may be strongly associated with ON in patients with SLE. Results of this review were considered in the development of recommendations for the diagnosis and monitoring of patients with SLE in Canada and will guide clinicians in their assessment of these patients.

Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions., (© 2016 American Heart Association, Inc.)