Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all-cause mortality: findings from the SMART-cohort.

BACKGROUND: Patients with type 2 diabetes (T2DM) are at higher risk of cardiovascular events and mortality. Multiple risk factors associated with T2DM have been identified which may confer this higher risk. The aim of this study is to quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all-cause mortality due to type 2 diabetes.

METHODS: Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2DM (insulin resistance, systolic blood pressure, renal function, LDL-cholesterol, triglycerides and micro-albuminuria) and which proportion of the effect of T2DM on cardiovascular events and all-cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2DM patients.

RESULTS: Only 35% (95%CI 15%-71%) of the excess cardiovascular risk due to T2DM is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance (proportion mediated effect (PME) 18%, 95%CI 3%-37%), followed by elevated triglycerides (PME 8%, 95%CI 4%-14%) and micro-albuminuria(PME 7%, 95%CI 3%-17%). Only 42% (95%CI 18%-73%) of the excess mortality risk was mediated by the classical risk factors considered. The largest mediated effect was by micro-albuminuria (PME 18%, 95%CI 10%-29%) followed by insulin resistance (PME 15%, 95%CI 1%-33%).

CONCLUSION: A substantial amount of the increased cardiovascular risk and all-cause mortality due to T2DM cannot be explained by traditional vascular risk factors. Future research should focus on identifying non-classical pathways which might further explain the increased cardiovascular and mortality risk due to T2DM. This article is protected by copyright. All rights reserved.