Insulin Resistance and Ischemic Stroke Outcomes

Insulin resistance, a metabolic state in which target tissues exhibit diminished responsiveness to insulin, has emerged as a key determinant of cerebral vascular health. In the context of ischaemic stroke, impaired insulin signalling contributes to endothelial dysfunction, pro-inflammatory cascades and altered cerebral perfusion, thereby influencing both acute injury and longer-term recovery. Measurements such as the homeostasis model assessment of insulin resistance (HOMA-IR) and the triglyceride-glucose (TyG) index serve as surrogate markers of systemic insulin resistance and have been linked to early neurological deterioration, functional outcomes and risk of recurrence. Mechanistically, insulin resistance amplifies oxidative stress and microvascular compromise during reperfusion, while also modulating platelet activity and thrombotic risk. Globally, the interplay between metabolic dysregulation and stroke prognosis underscores the need for integrated metabolic and neurological management, with potential applications in risk stratification and targeted therapeutic intervention.

Research from Nature Portfolio

Recent analyses in non-diabetic cohorts have demonstrated that elevated HOMA-IR scores correlate independently with poorer functional recovery following acute ischaemic stroke. Patients in the highest quartile of insulin resistance exhibited increased odds of unfavourable outcomes at discharge, even after adjustment for age, sex and stroke severity, highlighting insulin resistance as a modifiable prognostic factor. Complementing these findings, investigations into the TyG index in patients receiving intravenous thrombolysis have shown that higher TyG values predict increased mortality and reduced early neurological improvement at 90 days. These studies collectively affirm that markers of insulin resistance not only predict short-term functional status but also stratify risk in the acute management of ischaemic stroke.

Insulin Resistance and Ischemic Stroke Outcomes publication trend

The graph below shows the total number of articles in insulin resistance and ischemic stroke outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin resistance: A metabolic condition in which insulin fails to elicit its full biological response in peripheral tissues.

Homeostasis Model Assessment of Insulin Resistance (HOMA-IR): An index calculated from fasting glucose and insulin concentrations to estimate insulin sensitivity.

Triglyceride-Glucose (TyG) index: A composite marker of insulin resistance derived from fasting triglyceride and glucose levels.

Early Neurological Deterioration: Worsening of neurological status within days of stroke onset, often measured by changes in standardised stroke scales.

Mendelian randomisation: A genetic epidemiological method using inherited genetic variants to assess causal relationships between risk factors and disease outcomes.

References

1. Integrated single cell-RNA sequencing and Mendelian randomization for ischemic stroke and metabolic syndrome. iScience (2024).
2. Cerebral microvascular dysfunction in metabolic syndrome is exacerbated by ischemia–reperfusion injury. BMC Neuroscience (2017).
3. Insulin resistance is associated with poor functional outcome after acute ischemic stroke in non-diabetic patients. Scientific Reports (2021).
4. Association of triglyceride-glucose index with clinical outcomes in patients with acute ischemic stroke receiving intravenous thrombolysis. Scientific Reports (2022).
5. Association of triglyceride-glucose index with early neurological deterioration events in patients with acute ischemic stroke. Diabetology & Metabolic Syndrome (2023).
6. Association of triglyceride-glucose index with ischemic stroke recurrence in nondiabetic patients with small vessel occlusion: a multicenter hospital-based prospective cohort study. Cardiovascular Diabetology (2022).