Abstract
Disclosure: X. Li: None. L. Du: None. Y. Pan: None. X. Sun: None. Z. Huang: None. R. Zhang: None. S. Reutrakul: None. M.L. Daviglus: None. C. Li: None. L. Qi: None. J. He: None. L.A. Bazzano: None. B.T. Layden: None. T.N. Kelly: None. Background: A healthy sleep pattern (HSP) has been associated with lower risk of type 2 diabetes (T2D). However, the underlying metabolomic mechanisms linking the HSP and T2D are not well known. Therefore, we aim to identify the metabolomics signature of HSP and assess its relationship with T2D and glycemic traits among the Bogalusa Heart Study. Method: A total of 1184 participants from the Bogalusa Heart Study who underwent untargeted metabolomics profiling and had existing sleep data were included in the current analysis. HSP was estimated by five individual sleep factors, including sleep duration, chronotype, insomnia, and daytime sleepiness. Elastic net regularized regression was applied to generate an HSP-related metabolomics signature. T2D was defined as self-report, fasting glucose ≥126 mg/dL, HbA1c ≥6.5%, or were taking glucose-lowering medication. We applied logistic regression models for association between HSP-related metabolomics signature and T2D, and general linear regression models for fasting glucose and HbA1c. Results: The HSP was significantly inversely associated with the glucose (β: -4.69, SE: 0.97; p<0.001), HbA1c (β: -0.12, SE: 0.04; p<0.001), and the prevalence of T2D (OR: 0.85, 95% CI: 0.74 - 0.96, p=0.011). Using elastic net regularized regression, we identified a metabolomics signature, comprised of 44 metabolites, robustly associated with HSP (r=0.22, p<0.001). In the multivariable regression models, each SD increase in the HSP-related metabolomics signature was associated with lower levels of glucose (β: -6.55, SE: 1.24; p<0.001), HbA1c (β: -0.17, SE: 0.04; p<0.001), and lower levels of T2D (OR: 0.63, 95% CI: 0.51 - 0.78, p<0.001). Intriguingly, the associations persisted after further adjustment for the HSP: glucose (β: -5.65, SE: 0.1.31; p<0.001), HbA1c (β: -0.15, SE: 0.03; p<0.001), and the prevalence of T2D (OR: 0.64, 95% CI: 0.51 - 0.80, p<0.001). Conclusion: We identified a metabolomics signature that robustly reflected the HSP, and was significantly associated with lower prevalence of T2D and lower glycemic traits, independent of the traditional risk factors and phenotypic sleep measurements. The identified HSP-related metabolomics signature may enhance risk stratification and guide targeted efforts to improve sleep health and T2D. Presentation: Monday, July 14, 2025