| Title: | Association of the single-point insulin sensitivity estimator (SPISE) index and incident cardiovascular disease in early-stage CKM syndrome: insights from the UK biobank |
| Journal: | Diabetology & Metabolic Syndrome |
| Published: | 25 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42351199/ |
| DOI: | https://doi.org/10.1186/s13098-026-02222-z |
Publication 20529
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BackgroundInsulin resistance is a core metabolic abnormality driving the progression of cardiovascular-kidney-metabolic (CKM) syndrome. However, the gold-standard hyperinsulinemia-euglycemic clamp remains challenging for routine clinical use. The Single-Point Insulin Sensitivity Estimator (SPISE) index, calculated from HDL-C, triglycerides, and BMI without requiring insulin measurement, offers a simple and noninvasive alternative. However, its prognostic value for incident cardiovascular disease (CVD) in early-stage CKM syndrome (stages 0-3) has not been established.MethodsThis prospective cohort study included 391,793 participants from the UK Biobank with CKM stage 0-3. Participants were followed for a median of 7.6 years. Cox proportional hazards regression, and restricted cubic spline regression analyses were employed to examine the association between SPISE and incident CVD and coronary heart disease (CHD), adjusting for demographic, lifestyle, and clinical covariates. Subgroup analyses and sensitivity analyses were also conducted.ResultsDuring follow-up, 66,577 participants (17%) with stage 0-3 CKM syndrome experienced incident CVD, including 31,597 cases (8%) of CHD. SPISE demonstrated a significant L-shaped, inverse association with CVD risk, with an inflection point at 5.81 (P for nonlinearity < 0.001).Compared with the lowest tertile, the second and highest tertiles of SPISE were associated with 21% (HR 0.79, 95% CI 0.77-0.80) and 31% (HR 0.69, 95% CI 0.67-0.70) lower risk of incident CVD, respectively. The protective association was stronger for CHD, with corresponding HRs of 0.73 (95% CI 0.71-0.75) and 0.54 (95% CI 0.52-0.55). Subgroup analyses revealed more pronounced benefits among younger participants (< 45 years; HR 0.71, 95% CI 0.68-0.74 for CVD) and never/previous smokers (P for interaction < 0.005).ConclusionIn this large population-based study, higher SPISE index was independently and nonlinearly associated with lower risk of incident CVD and CHD in patients with early-stage CKM syndrome. The SPISE index may serve as a practical, cost-effective tool for cardiovascular risk stratification and early prevention in this high-risk population.Graphical abstract</p>
10 Authors
- Jie Zou
- Zhoujian Han
- Yuexin Pan
- Zeru Chen
- Hongyu Zhong
- Rongshuai Pan
- Jingquan Zhou
- Jie Xiao
- Xiaoqian Wu
- Mingyan Li
1 Application
| Application ID | Title |
|---|---|
| 220028 | Exploring the contribution of lifestyle interventions on the risk of Metabolic Diseases, Cardiovascular Disease and Neurodegenerative Disorders |
Enabling scientific discoveries that improve human health