Cardiovascular Risks in Prediabetes and Impaired Glucose Tolerance

Prediabetes represents an intermediate metabolic state characterised by blood glucose levels above normal but below the threshold for a diabetes diagnosis. It encompasses impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycated haemoglobin (HbA1c) within specific ranges. Insulin resistance, endothelial dysfunction and a low-grade inflammatory milieu underlie accelerated atherogenesis in this population. Individuals with prediabetes display a continuum of cardiovascular risk that spans coronary artery disease, cerebrovascular events, peripheral artery disease and heart failure. Risk factors such as advanced age, obesity, hypertension and dyslipidaemia frequently co-exist, amplifying vascular injury via dysregulated lipid metabolism, oxidative stress and pro-thrombotic pathways. Epidemiological data suggest that even modest elevations in fasting or post-load glucose correlate with subclinical endothelial dysfunction and arterial stiffness, presaging overt clinical events. International prevalence estimates exceed 350 million people, imposing a burgeoning public health burden. Early recognition and stratified intervention, ranging from targeted lifestyle modification to pharmacotherapy, may attenuate progression along both glycaemic and cardiovascular trajectories, underscoring the need for refined screening and risk-stratification strategies.

Research from Nature Portfolio

A recent causal inference analysis has delineated the direct contribution of early dysglycaemia to vascular pathology. While observational studies broadly linked prediabetes to multiple organ complications, robust causal modelling demonstrated that prediabetes is specifically causative of coronary artery disease rather than other complications such as stroke or chronic kidney disease. This finding refines the understanding of the temporal sequence and suggests that preventive measures aimed at normalising glucose levels may yield greatest benefit in the prevention of coronary atherosclerosis.

Cardiovascular Risks in Prediabetes and Impaired Glucose Tolerance publication trend

The graph below shows the total number of articles in cardiovascular risks in prediabetes and impaired glucose tolerance across all publications each year (not limited to Nature Index journals).

Technical terms

Prediabetes: Intermediate hyperglycaemia with glucose or HbA1c levels below diabetic thresholds.

Impaired Fasting Glucose (IFG): Fasting plasma glucose between 5.6 and 6.9 mmol/L.

Impaired Glucose Tolerance (IGT): Plasma glucose of 7.8–11.0 mmol/L two hours after a standard oral glucose load.

Glycated Haemoglobin (HbA1c): Percentage of haemoglobin bound to glucose, reflecting average blood glucose over two to three months.

Major Adverse Cardiovascular Events (MACE): Composite endpoint including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke.

Major Adverse Limb Events (MALE): Composite of peripheral revascularisation, major amputation or limb-threatening ischaemia.

References

1. Prediabetes increases the risk of major limb and cardiovascular events. Cardiovascular Diabetology (2023).
2. Global epidemiology of prediabetes - present and future perspectives. Clinical Diabetes and Endocrinology (2019).
3. Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies. Diabetologia (2021).
4. An investigation of causal relationships between prediabetes and vascular complications. Nature Communications (2020).