ArticleFrontiers in endocrinology2026
A dose-response relationship between low-density lipoprotein cholesterol levels within the normal range and the incidence of diabetes mellitus: a retrospective cohort study.
Article in Frontiers in endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Despite the established link between elevated Low-density lipoprotein cholesterol (LDL-C) and diabetes, the association of LDL-C levels within the normal range with diabetes is poorly characterized. This study aimed to investigate the relationship between normal-range LDL-C levels and the incidence of new-onset diabetes. Methods: In this retrospective cohort study, a total of 98,857 individuals with normal LDL-C levels (≤3.4 mmol/L) were enrolled between 2010 and 2016. The association was assessed using Cox proportional hazards regression models. Restricted cubic splines were utilized to examine dose-response relationships and potential nonlinearity. Subgroup analyses were pre-specified by age, sex, and Body mass index (BMI). Results: During a median follow-up of 3.1 years, 2,107 incident diabetes cases were documented. After multivariable adjustment, participants in the highest level of LDL-C (G4: 2.6-3.4 mmol/L) had a significantly increased risk of diabetes compared to those in the lowest level (G1: 0-1.4 mmol/L), with an adjusted hazard ratios (HR) of 2.11 [95% confidence interval (CI): 1.32-3.38, P = 0.002]. A clear dose-response relationship was observed. Notably, the risk of incident diabetes increased significantly once LDL-C levels exceeded approximately 1.8 mmol/L (Adjusted HR = 1.93, 95% CI: 1.64-2.28, P<0.001). This association remained consistent across all pre-specified subgroups. Discussion: Among individuals with normal LDL-C levels, higher LDL-C is an independent, dose-dependent risk factor for new-onset diabetes. Maintaining LDL-C below a threshold of approximately 1.8 mmol/L may be associated with a lower diabetes risk, suggesting its potential role in refining primary prevention strategies.
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