Association of carotid atherosclerosis markers with all-cause and cardiovascular disease-specific mortality in persons with type 2 diabetes: a causal mediation analysis with glucose variation.

ABSTRACT

AIMS: Glucose variation (GV) is independently associated with mortality in patients with diabetes. However, no study has examined the effects of carotid atherosclerosis markers on mortality after considering GV. Our purpose is to investigate the independent effects of carotid atherosclerosis markers in persons with type 2 diabetes (T2DM) after considering GV and the mediation effects of carotid atherosclerosis markers on associations between GV with cardiovascular disease (CVD) mortality. MATERIALS AND METHODS: This study is a retrospective cohort study including 3628 persons with T2DM who were admitted to a medical center between January 01, 2001 and October 31, 2021. GV was defined as a coefficient of variation (CV) of repeated measurements within a year before the index date (date of first IMT assessment). Carotid atherosclerosis markers included intima-media thickness (IMT), plaque, and stenosis. The outcomes consisted of all-cause and expanded cardiovascular disease (CVD) mortality. Cox proportional hazards models were applied. RESULTS: Among the participants, 286 (7.9%) had IMT ≥ 2 mm, 2834 (78.1%) had carotid plaque, and 464 (12.8%) had carotid stenosis ≥ 50%. When GV was considered, IMT, carotid plaque, and carotid stenosis were significant factors for all-cause mortality (except IMT considering HbA1c-CV) and expanded CVD mortality. IMT was a significant mediator in the associations of fasting plasma glucose (FPG)-CV with all-cause and expanded CVD mortality (2 and 3.19%, respectively), and carotid stenosis was a significant mediator in the association between FPG-CV and expanded CVD mortality (3.83%). CONCLUSIONS: Our statistical evaluations show suggests that carotid atherosclerosis markers are important predictors of CVD mortality in persons with T2DM if GV is considered. In addition, IMT and carotid stenosis were significant mediators in the association between GV and mortality.