Corresponding to 55% higher fasting insulin adjusted for body mass index, 0.46 mmol/L lower high-density lipoprotein cholesterol and 0.89 mmol/L higher triglyceride, one standard deviation change in genetically predicted IR was associated with increased risk of hypertension (odds ratio (OR) 1.06, 95% CI 1.04–1.08; P = 1.91 × 10–11) and PAD (OR 1.90, 95% CI 1.43–2.54; P = 1.19 × 10–5). This evidence concerns the gene INS and peripheral arterial disease.