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Glycaemic variability underlies myocyte dysfunction and myocardial injury risk in diabetes

ABSTRACT: This study evaluates mechanisms of glycaemic stress underpinning cardiovascular risk in diabetes. Using in vitro and in vivo models, we demonstrate that glycaemic variability rather than hyperglycaemia alone is a dominant risk factor for heart muscle dysfunction and myocardial injury sensitivity in diabetes. These findings provide new preclinical models for mechanistic and drug discovery studies and inform strategies for managing cardiovascular outcomes in patients with diabetes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279917 | GEO | 2025/12/14

REPOSITORIES: GEO

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Glycaemic variability identified as a critical determinant of myocyte dysfunction and risk for myocardial injury in preclinical models of diabetes

Project description:Heart disease is the leading cause of morbidity and mortality in individuals with diabetes, due largely to risks associated with ischaemic injuries such as myocardial infarction (MI). We use human population genetic data to demonstrate that current biomarkers of hyperglycaemia do not account for risk of post-MI mortality in diabetes patients. This study therefore systematically evaluates glycaemic stress underpinning cardiovascular risk in diabetes. Using in vivo and in vitro models, we demonstrate that glycaemic variability rather than hyperglycaemia alone is a dominant risk factor for heart muscle dysfunction and myocardial injury sensitivity in diabetes. These findings provide new preclinical models for mechanistic and drug discovery studies and inform strategies for managing cardiovascular outcomes in patients with diabetes.

2026-02-06 | MTBLS11411 | MetaboLights

Glycaemic variability underlies myocyte dysfunction and myocardial injury risk in diabetes

Project description:Glycaemic variability underlies myocyte dysfunction and myocardial injury risk in diabetes

| PRJNA1175386 | ENA

Effects of diets high in animal or plant protein on oxidative stress in individuals with type 2 diabetes: a randomized clinical trial

Project description:High-protein diet is a promising strategy for diabetes treatment supporting body weight control, improving glycaemic status, cardiovascular risk factors and reducing liver fat. In this work, we investigated effects of diets high in animal (AP) or plant (PP) protein on oxidative stress and antioxidant status in individuals with type 2 diabetes (T2DM).

2019-12-14 | E-MTAB-8549 | biostudies-arrayexpress

Expression data from mouse aorta during and following transient hyperglycaemia

Project description:Immediate and early effects of transient hyperglycaemia were examined using fully- reversible transgenic diabetic mice. Transient hyperglycaemia altered expression of 769 arterial genes, of which 200 did not reverse following recovery from hyperglycaemia. Many such genes are known to promote atherogenesis, including several implicated in arterial calcification and inflammation. This supports the view that hyperglycaemia causes not only very early deleterious changes in arterial gene expression but that to a large extent these persist for some time after restoration of normal blood glucose levels in vivo. Together, results support the contention that avoiding excess CVD risk in diabetes requires very early correction of hyperglycaemia.

2010-08-09 | GSE15401 | GEO

Immune dysfunction in intermediate hyperglycaemia and diabetes patients in tuberculosis

Project description:People living with diabetes have an increased risk of developing active tuberculosis. The effects of diabetes (HbA1c ≥6.5%) and intermediate hyperglycaemia (HbA1c 5.7-6.5%), on this transcriptomic signature were investigated by RNA-seq, to enhance understanding of immunological susceptibility in diabetes-tuberculosis comorbidity.Diabetes increased the magnitude of gene expression change in the host transcriptome in tuberculosis, characterised by an increase in innate, and decrease in adaptive immune responses. Strikingly, patients with intermediate hyperglycaemia and tuberculosis exhibited blood transcriptomes much more similar to diabetes-tuberculosis patients than to uncomplicated tuberculosis patients. Aberrant transcriptomes unveil a susceptibility mechanism of DM patients to TB of enhanced inflammation and reduced interferon responses.

2020-07-16 | GSE114192 | GEO

Peripheral Blood Monocyte Gene Expression in Recent-Onset Type 1 Diabetes

Project description:OBJECTIVE: Novel biomarkers of disease progression after type 1 diabetes onset are needed. RESEARCH DESIGN AND METHODS: We profiled peripheral blood (PB) monocyte gene expression in 6 healthy subjects and 16 children with type 1 diabetes diagnosed ~3 months previously, and analyzed clinical features from diagnosis to 1 year. RESULTS: Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy controls, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA1c levels during the first year, compared to patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g. induction of HIF1A, DDIT3, DDIT4 and GRP78). qPCR quantitation of a 9-gene panel correlated with glycaemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. CONCLUSIONS: A PB gene expression signature correlates with glycaemic control in the first year after diabetes diagnosis, and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset, and systemic stresses as contributors to innate immune function in type 1 diabetes. CD14+ monocytes from a total of 16 children with recent-onset type 1 diabetes and 6 adult healthy controls were profiled in 2 independent microarrays.

2012-05-31 | E-GEOD-33440 | biostudies-arrayexpress

Impaired resolution of blood transcriptomes through tuberculosis treatment with diabetes comorbidity

Project description:People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB-diabetes (TB-DM) co-morbidity have excessive inflammatory and reduced interferon responses at TB diagnosis. It is unknown whether this persists through treatment, potentially underlying adverse outcomes. Methods Pulmonary TB patients were recruited in South Africa, Indonesia and Romania, and classified as having TB-DM, TB with prediabetes, TB-related hyperglycaemia or uncomplicated TB, based on glycated haemoglobin (HbA1c) concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood samples collected at diagnosis and at regular intervals throughout treatment was measured by unbiased RNA-Seq and targeted Multiplex Ligation-dependent Probe Amplification. Results Gene expression was modulated by TB treatment in all groups but to different extents, such that differences remained in people with TB-DM relative to TB-only throughout, including genes involved in innate responses, anti-microbial immunity and the inflammasome. People with prediabetes or with TB-related hyperglycaemia had gene expression more similar to people with TB-DM than TB-only throughout treatment. The overall pattern of change was similar across clinical groups irrespective of glycaemic index, permitting models predictive of TB treatment to be developed. Conclusions The exacerbated transcriptome changes seen in TB-DM take longer to resolve during TB treatment, indicating that prolonged treatment or host-directed therapy may be needed to improve TB treatment outcomes. Development of transcriptome-based biomarker signatures of TB-treatment response should include people with diabetes to be useful across populations.

2023-09-05 | GSE193978 | GEO

Serum Alpha-2-Macroglobulin Links Type 1 Diabetes Status and Incident Cardiovascular Disease

Project description:Background: Cardiovascular disease (CVD) is a leading cause of mortality in individuals with type 1 diabetes mellitus (T1DM), with conventional risk factors not fully explaining the heightened risk. Study Design: We conducted a cross-sectional study comparing serum protein levels in 134 participants with T1DM from the Coronary Artery Calcification in Type 1 Diabetes study to 47 healthy controls, followed by a case-cohort study among 181 T1DM participants, including 47 with CVD events. Linear regression analyzed serum protein levels by diabetes status, while Cox proportional hazards regression assessed associations with incident CVD. Findings: Among 28 serum proteins tested, five showed significant differences between T1DM patients and controls, with alpha-2-macroglobulin (A2M) being notably 1.6-fold higher in T1DM. Adjusted models revealed that A2M (mean hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.5-4.1) and apolipoprotein C3 (APOC3, mean HR 1.7, 95% CI 1.1-2.7) were independently associated with incident CVD in T1DM. Conclusions: Elevated serum levels of A2M in T1DM suggest its potential role as a marker—and possibly a mediator—of CVD risk in these patients, alongside APOC3. These findings underscore the significance of specific serum proteins in understanding and managing CVD risk in T1DM.

2025-02-11 | PXD054039 | panorama

Peripheral Blood Monocyte Gene Expression in Recent-Onset Type 1 Diabetes

2012-06-01 | GSE33440 | GEO

Multi-organ single-cell RNA-sequencing of early hyperglycaemia responses

Project description:Diabetes causes a range of complications that can affect multiple organs. Hyperglycaemia is an important driver of diabetes-associated complications, mediated by biological processes such as dysfunction of endothelial cells, fibrosis and alterations in leukocyte number and function. Here, we dissected the transcriptional response of key cell types to hyperglycaemia across multiple tissues using single-cell RNA-seq.

2024-10-18 | GSE244475 | GEO

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