Non-Linear Relationship Between High-Density Lipoprotein Cholesterol and Incident of Diabetes Mellitus: A Secondary Retrospective Analysis Based on A Japanese Cohort Study

Abstract 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. A total of 15388 study participants from Murakami Memorial Hospital in Japan included all medical records for participants who received medical examinations from 2004 to 2015. The target-independent variable and the dependent variable were HDL-C measured at baseline, and DM incident appeared during follow-up, respectively. Covariates involved in this study included gender, age, ethanol consumption, smoking status, regular exerciser, systolic blood pressures, diastolic blood pressures, body mass index, waist circumference, fatty liver, total cholesterol, triglycerides, hemoglobin A1c, fasting plasma glucose. 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 gender, age, ethanol consumption, smoking status, regular exerciser, systolic blood pressures, diastolic blood pressures, body mass index, waist circumference, total cholesterol, triglycerides, hemoglobin A1c, fasting plasma glucose, the result showed HDL-C was negatively associated with incident of DM (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 of DM, which had an inflection point of HDL-C was 1.72mmol/L. The effect sizes and the confidence intervals on the left and right sides of the inflection point were 0.36 (0.21, 0.59) and 2.90 (0.96, 8.75). Subgroup analysis showed a stronger association could be found in the population with the ex-smoker and current-smoker. The same trend was also seen in the community with hypertension (P for interaction = 0.010, HR = 1.324). Conclusion: HDL-C is negatively associated with DM risk. The relationship between HDL-C and incident of DM is also non-linear. HDL-C was strongly negatively related to the incident of diabetes when HDL-C is less than 1.72mmol/L.