Associations of cumulative exposure and control patterns of the single-point insulin sensitivity estimator with incident cardiovascular disease in middle-aged and older Chinese adults with dysglycemia

OBJECTIVE: the single-point insulin sensitivity estimator (SPISE) is a novel insulin resistance marker; however, the longitudinal impacts of cumulative SPISE (cuSPISE) and its control patterns on cardiovascular disease (CVD) remain unclear. We investigated the associations of SPISE, cuSPISE, and its longitudinal control patterns with incident CVD in middle-aged and older adults with dysglycemia (diabetes or prediabetes). METHODS: data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). Long-term SPISE exposure and its longitudinal control patterns were characterized using cuSPISE and k-means clustering. Multivariable Cox models, restricted cubic splines (RCS), subgroup, and mediation analyses were employed to evaluate the associations between SPISE and incident CVD. RESULTS: during a median 5-year follow-up of 2,598 participants, 575 incident CVD cases were identified. SPISE and cuSPISE were inversely associated with CVD risk. Compared with the lowest cuSPISE quartile (Q1), the highest (Q4) showed a 40 % lower risk (HR = 0.60; 95 % CI: 0.44-0.81; p for trend < 0.001). RCS analysis further confirmed this inverse relationship. Furthermore, well-controlled group (HR = 0.74; 0.55-0.99, p = 0.048) and moderately-controlled group (HR = 0.80; 0.65-0.98, p = 0.031) trends were associated with lower CVD incidence than the poorly-controlled group (Cluster 3). White Blood Cell (WBC) mediated 4.49 % of the cuSPISE-CVD association. Findings remained consistent across subgroups. CONCLUSION: our findings suggest that higher SPISE and cuSPISE levels, along with well-controlled or moderately-controlled groups, are associated with a reduced risk of CVD. These results suggest that longitudinal monitoring of SPISE may provide valuable insights for CVD risk stratification among middle-aged and older populations with dysglycemia.