Mutual effect modification between adiponectin and HDL as risk factors of cardiovascular events in Type 2 diabetes individuals: a cohort study

Purpose: We aimed to assess whether high-density lipoprotein (HDL) cholesterol modifies the association between adiponectin and incident cardiovascular (CV) morbidity and mortality in Type 2 Diabetes Mellitus (T2DM) and vice versa. Methods: At baseline, 106 T2DM participants with various degrees of renal function were enrolled and followed up over a period of 7 years with fatal/nonfatal CV events as outcome. Results: During the follow-up, 49 participants experienced incident CV events (28 fatal, 21 nonfatal). On univariate Fine and Gray sub-hazard models, HDL cholesterol was a strong modifier of the association between adiponectin and CV outcomes both on crude (P = 0.011) and gender- and eGFR-adjusted models (P = 0.010). The protective effect for CV events portended by a fixed increase in adiponectin (1 ?g/ml) was progressively higher across increasing values of HDL cholesterol. Moreover, plasma adiponectin also modified the protective effect of HDL on CV outcomes both in crude and multivariate analyses. We found a mutual effect modification between adiponectin and HDL as risk factors of CV events in participants with T2DM. Conclusion: Our results are coherent with the hypothesis that HDL cholesterol might play a pivotal role in the interpretation of the association between adiponectin and the risk of adverse CV outcomes in this population.