Abstract
Mendelian randomization (MR) suggests post-prandial hyperinsulinemia (unadjusted for plasma glucose) increases body mass index (BMI) but its impact on cardiometabolic disease (CMD), a leading cause for mortality and morbidity in people with obesity, is not established. Fat distribution, i.e. increased centripetal and/or reduced femoro-gluteal adiposity, is causally associated with and better predicts CMD than BMI. We therefore undertook bi-directional MR to assess the effect of corrected insulin response (CIR, insulin 30 minutes after a glucose challenge adjusted for plasma glucose) on BMI, waist–to-hip ratio (WHR), leg fat, type 2 diabetes (T2D), triglyceride (TG), high-density lipoprotein (HDL), liver fat, hypertension and CAD in people of European descent.
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