Higher plasma dicarbonyl levels are associated with liver fibrosis in obese individuals.

Introduction: Methylglyoxal (MGO) is a very reactive compound that modifies proteins, forming advanced glycation end products (AGEs) and activating inflammatory pathways. Elevated MGO levels have been linked to various diseases, including type 2 diabetes and atherosclerosis. However, the role of MGO and other glycating agents in the progression of liver fibrosis in the setting of metabolic dysfunction associated steatotic liver disease (MASLD) is poorly understood.

Does Gut Microbial Methylglyoxal Metabolism Impact Human Physiology?

Methylglyoxal (MGO) is a highly reactive dicarbonyl associated with oxidative stress, inflammation, and chronic diseases, particularly diabetic vascular complications and atherosclerosis through the formation of advanced glycation end products (AGEs). In the setting of human/host diseases, the formation of MGO has mainly been considered as the byproduct of glycolysis. Gut microbes play an important role in the development of cardiometabolic diseases.

Downregulation of LATS1/2 Drives Endothelial Senescence-Associated Stemness (SAS) and Atherothrombotic Lesion Formation.

Background: Atherothrombosis, the main event leading to acute coronary syndrome (ACS), is strongly linked to disturbed blood flow (d-flow) regions. Although the involvement of the Hippo pathway and its kinases Large Tumor Suppressor Kinase 1and 2 (LATS 1 and 2) in mechanical stress responses is known, the mechanisms by which d-flow simultaneously induces senescence, proliferation, and atherothrombosis remain unclear.

Methods: The role of endothelial cells (EC)-specific LATS1/2 was examined using EC specific knock-out (EKO) mice in a partial left carotid ligation (PLCL) model.

Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus.

Aims: As compared with C-peptide, plasma proinsulin levels in individuals with long-standing type 1 diabetes mellitus are relatively understudied, but may serve as a marker of stressed, yet alive β-cells.

Materials And Methods: We measured proinsulin and C-peptide levels (detection limit <0.15 pmol/L and <0.

Kidney Disease: The Forgotten Legacy of Type 1 Diabetes.

Type 1 diabetes is associated with a progressive decline in kidney function. With improved survival, more individuals with type 1 diabetes are reaching an age where irreversible loss of kidney function can impact health and clinical outcomes. Although current standard of care has markedly reduced the incidence of fast-progressing kidney disease characterized by heavy albuminuria, and improved patient survival, these same interventions have not slowed kidney decline in most patients.

Antithrombotic Therapy and Mortality Risk in Older Adults with Hip Fractures.

Objectives: Antithrombotic therapy, including antiplatelet therapy, direct oral anticoagulants (DOACs), and vitamin K antagonists (VKAs), is increasingly prescribed. These therapies pose complex challenges in patients with hip fracture due to risks of bleeding, risks of thromboembolism, and their potential role as markers of frailty. However, limited real-world evidence exists regarding their risks and benefits in this population.

Accelerated atherosclerosis associated with immune checkpoint inhibitors: a systematic review and meta-analysis of pre-clinical studies.

Background: Patients with cancer treated with immune checkpoint inhibitors are at increased risk of myocardial infarction and ischemic stroke. The mechanism is incompletely understood but may involve accelerated atherosclerosis due to enhanced inflammation. Pre-clinical studies may provide insight in these mechanisms.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Are the lipid-lowering effects of incretin-based therapies relevant for cardiovascular benefit?

Purpose Of Review: This review examines the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on lipid profiles in individuals with type 2 diabetes mellitus and/or obesity, crucial for optimizing cardiovascular risk management.

Recent Findings: GLP-1RAs affect lipid levels by reducing intestinal apolipoprotein B48 production and mesenteric lymph flow, while increasing catabolism of apolipoprotein B100. It remains unknown whether these effects are direct or indirect, but the improvements in lipid levels are strongly correlated to the drug-induced weight loss.

Higher fibre and lower carbohydrate intake are associated with favourable CGM metrics in a cross-sectional cohort of 470 individuals with type 1 diabetes.

Aims/hypothesis: The aim of this work was to investigate the association between macronutrient intakes and continuous glucose monitoring (CGM) metrics in individuals with type 1 diabetes.

Methods: In 470 individuals with type 1 diabetes of the GUTDM1 cohort (65% female, median age 40 [IQR 28-53] years, median diabetes duration 15 [IQR 6-29] years), we used logistic regression to establish associations between macronutrient intakes and the CGM metrics time in range (TIR, time spent between 3.9-10.

Associations between diabetes-related genetic risk scores and residual beta cell function in type 1 diabetes: the GUTDM1 study.

Aims/hypothesis: Use of genetic risk scores (GRS) may help to distinguish between type 1 diabetes and type 2 diabetes, but less is known about whether GRS are associated with disease severity or progression after diagnosis. Therefore, we tested whether GRS are associated with residual beta cell function and glycaemic control in individuals with type 1 diabetes.

Methods: Immunochip arrays and TOPMed were used to genotype a cross-sectional cohort (n=479, age 41.

Can fecal microbiota transplantations modulate autoimmune responses in type 1 diabetes?

Type 1 diabetes (T1D) is a chronic autoimmune disease targeting insulin-producing pancreatic beta cells. T1D is a multifactorial disease incorporating genetic and environmental factors. In recent years, the advances in high-throughput sequencing have allowed researchers to elucidate the changes in the gut microbiota taxonomy and functional capacity that accompany T1D development.

Prevalence and predictive features of metabolic dysfunction-associated steatotic liver disease in type 1 diabetes.

Aims/hypothesis: The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity.

Methods: A total of 453 individuals with type 1 diabetes (41.

Tryptophan metabolites and incident cardiovascular disease: The EPIC-Norfolk prospective population study.

Background And Aims: Cardiovascular disease (CVD) remains the largest cause of death globally due to various risk factors. One novel potential contributor to CVD might be the metabolism of the essential amino acid tryptophan (Trp), which through many pathways can produce immunomodulatory metabolites such as kynurenine, indole-3-propionate and serotonin. We aim to identify the metabolites with the strongest association with cardiovascular disease, utilizing a substantial and diverse cohort of individuals.

Atorvastatin lowers Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes.

Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than F-fluorodeoxyglucose (F-FDG).

Residual β-Cell Function Is Associated With Longer Time in Range in Individuals With Type 1 Diabetes.

Objective: Little is known about the influence of residual islet function on glycemic control in type 1 diabetes (T1D). We investigated the associations between residual β-cell function and metrics of continuous glucose monitoring (CGM) in individuals with T1D.

Research Design And Methods: In this cross-sectional cohort comprising 489 individuals (64% female, age 41.

Ancestral and environmental patterns in the association between triglycerides and other cardiometabolic risk factors.

Background: West Africans and African Americans with substantial (∼80%) West African ancestry are characterized by low levels of triglycerides (TG) compared to East Africans and Europeans. The impact of these varying TG levels on other cardiometabolic risk factors is unclear. We compared the strength of association between TG with hypertension, blood pressure, BMI, waist circumference, type 2 diabetes (T2D), and fasting glucose across West African (WA), East African (EA), and European (EU) ancestry populations residing in three vastly different environmental settings: sub-Saharan Africa, United States, and Europe.

Pyridoxamine prevents increased atherosclerosis by intermittent methylglyoxal spikes in the aortic arches of ApoE mice.

Methylglyoxal (MGO) is a reactive glucose metabolite linked to diabetic cardiovascular disease (CVD). MGO levels surge during intermittent hyperglycemia. We hypothesize that these MGO spikes contribute to atherosclerosis, and that pyridoxamine as a MGO quencher prevents this injury.

Pyridoxamine reduces methylglyoxal and markers of glycation and endothelial dysfunction, but does not improve insulin sensitivity or vascular function in abdominally obese individuals: A randomized double-blind placebo-controlled trial.

Aim: To investigate the effects of pyridoxamine (PM), a B6 vitamer and dicarbonyl scavenger, on glycation and a large panel of metabolic and vascular measurements in a randomized double-blind placebo-controlled trial in abdominally obese individuals.

Materials And Methods: Individuals (54% female; mean age 50 years; mean body mass index 32 kg/m ) were randomized to an 8-week intervention with either placebo (n = 36), 25 mg PM (n = 36) or 200 mg PM (n = 36). We assessed insulin sensitivity, β-cell function, insulin-mediated microvascular recruitment, skin microvascular function, flow-mediated dilation, and plasma inflammation and endothelial function markers.

Associations between presence of diabetes, mortality and fracture type in individuals with a hip fracture.

Aims: An overlooked aspect of diabetes is an increased risk of hip fractures, with associated mortality. We investigated whether fracture type and/or burden of comorbidities explains the increased risk of mortality in diabetes after hip fracture.

Methods: For this cohort study, we used a de-identified data set of hip fracture patients registered in a quality-of-care registry (2017/2018) included in Maastricht University Medical Centre.

Neutrophil Migratory Patterns: Implications for Cardiovascular Disease.

The body's inflammatory response involves a series of processes that are necessary for the immune system to mitigate threats from invading pathogens. Leukocyte migration is a crucial process in both homeostatic and inflammatory states. The mechanisms involved in immune cell recruitment to the site of inflammation are numerous and require several cascades and cues of activation.

Fecal microbiota transplantation and fiber supplementation, better together?

Fecal microbiota transplantation (FMT) is emerging as a tool to study the microbiome and as a potential treatment for several non-infectious diseases. Recently, Mocanu et al. showed that supplementing low fermentable fiber after FMT may improve insulin sensitivity in severely obese individuals.

Neutrophils in cardiovascular disease: warmongers, peacemakers, or both?

Neutrophils, the most abundant of all leucocytes and the first cells to arrive at the sites of sterile inflammation/injury act as a double-edged sword. On one hand, they inflict a significant collateral damage to the tissues and on the other hand, they help facilitate wound healing by a number of mechanisms. Recent studies have drastically changed the perception of neutrophils from being simple one-dimensional cells with an unrestrained mode of action to a cell type that display maturity and complex behaviour.