Insulin resistance mediates obesity-related risk of cardiovascular disease: a prospective cohort study
Abstract
Background The mechanisms linking obesity to cardiovascular disease (CVD) are still not clearly defined. Individuals who are overweight or obese often develop insulin resistance, mediation of the association between obesity and CVD through the insulin resistance seems plausible and has not been investigated. This study aimed to evaluate whether and to what extend the effect of general and central obesity on cardiovascular disease (CVD) is mediated by insulin resistance. Methods A total of 94,136 participants without CVD at baseline were recruited from the Kailuan study. Insulin resistance was evaluated by the triglyceride-glucose (TyG) index, calculating as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Mediation analysis using a new 2-stage regression method for survival data proposed by Valeri and VanderWeele was to explore the mediating effects of the TyG index on the association between obesity and CVD. Results During a median follow-up of 13.01 years, we identified 7327 cases of CVD. Mediation analyses showed that 47.81% of the total association (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.12–1.24) between overweight and CVD was mediated through the TyG index (HR [indirect association], 1.07; 95% CI, 1.07–1.09), and the proportion mediated was 37.94% for general obesity. For central obesity, analysis by waist circumference, waist/hip, and waist/height categories yielded an attenuated proportion mediated of 32.01, 35.02, and 31.06% for…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 94,136 participants or records.
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