Insulin resistance increases stroke risk: a cross-sectional study from NHANES 1999–2018 and a Mendelian randomization study

Existing evidence suggested a relevance between insulin resistance (IR) and stroke, but further confirmation is needed. Research priorities encompass large sample size, stratified analysis, advanced IR index, stroke subtype characterization, and analysis of potential mechanisms.
We applied multivariable logistic regression using data from National Health and Nutrition Examination Survey 1999–2018 to estimate the correlation between two IR indexes: metabolic score for insulin resistance (METS-IR) and homeostasis model assessment of insulin resistance (HOMA-IR), and stroke. We also performed a two-sample Mendelian randomization (MR) study to detect the causal relationship between IR phenotype, METS-IR, and HOMA-IR as exposures, and stroke as well as its ischemic subtypes as outcomes.
A total of 15,016 participants representing 147,325,838 individuals after weighting were enrolled. Both METS-IR and HOMA-IR were not significantly correlated with stroke after strict adjustment, but METS-IR was strongly related to stroke in individuals aged 20–40 in the stratification analysis. The MR analysis showed robust causal associations between IR phenotype and any stroke (AS) as well as ischemic stroke (IS). Besides AS and IS, METS-IR also had a causal effect on large artery stroke and small vessel stroke.
IR was associated with an increased risk of stroke in young adults.