Non-linear relationship between high-density lipoprotein cholesterol and incident diabetes mellitus: a secondary retrospective analysis based on a Japanese cohort study.

Background And Objective: High-density lipoprotein cholesterol (HDL-C) may be directly involved in glucose metabolism by enhancing insulin sensitivity and insulin secretion. This current study aimed to explore the association between HDL-C and the risk of diabetes mellitus (DM) in Japanese population.

Methods: This retrospective cohort study was based on a publicly available DRYAD dataset. We enrolled 15,388 Japanese participants who received medical examinations from 2004 to 2015 at Murakami Memorial Hospital. Our study selected HDL-C at baseline and incident DM during follow-up as the target independent variable and the dependent variable, respectively. Cox proportional-hazards regression was used to investigate the association between HDL-C and DM, generalized additive models to identify non-linear relationships.

Results: After adjusting for the demographic and clinical covariates, the result showed low HDL-C levels were associated with increased risk for diabetes (HR = 0.54, 95%CI (0.35, 0.82)). The results remained robust in a series of sensitive analysis. A non-linear relationship was detected between HDL-C and incident DM with an inflection point of HDL-C at 1.72 mmol/L (Log-likelihood ratio test P = 0.005). Subgroup analysis showed that a stronger association could be found in ex-smokers and current-smokers. The same trend was also seen in the community with hypertension (P for interaction = 0.010, HR = 1.324).

Conclusion: This study demonstrates a negative and non-linear relationship between HDL-C and diabetes in the Japanese population. There is a threshold effect between HDL-C and diabetes. When HDL-C is lower than 1.72 mmol/L, the decreased HDL-C levels were associated with an increased risk for diabetes.