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Mediation analysis of the relationship between type 2 diabetes and cardiovascular events and all‐cause mortality: Findings from the SMART cohort
Author(s) -
Sharif Shahnam,
Groenwold Rolf H. H.,
Graaf Yolanda,
Berkelmans Gijs F. N.,
Cramer Maarten J.,
Visseren Frank L. J.,
Westerink Jan
Publication year - 2019
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13759
Subject(s) - albuminuria , medicine , insulin resistance , type 2 diabetes , cohort , mediation , diabetes mellitus , cohort study , endocrinology , blood pressure , disease , cardiology , risk factor , insulin , political science , law
Aim To quantify the magnitude and specific contributions of known cardiovascular risk factors leading to higher cardiovascular risk and all‐cause mortality caused by type 2 diabetes (T2D). Methods Mediation analysis was performed to assess the relative contributions of known classical risk factors for vascular disease in T2D (insulin resistance, systolic blood pressure, renal function, LDL‐cholesterol, triglycerides and micro‐albuminuria), and what proportion of the effect of T2D on cardiovascular events and all‐cause mortality these factors mediate in the Second Manifestations of ARTerial disease (SMART) cohort consisting of 1910 T2D patients. Results Only 35% (95% CI 15‐71%) of the excess cardiovascular risk caused by T2D is mediated by the classical cardiovascular risk factors. The largest mediated effect was through insulin resistance [proportion of 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 caused by T2D cannot be explained by traditional vascular risk factors. Future research should focus on identifying non‐classical pathways that might further explain the increased cardiovascular and mortality risk caused by T2D.