Association between high-density lipoprotein cholesterol and the risk of incident diabetes in the prediabetic and the normoglycemic Japanese men: A population-base longitudinal cohort study

Background While many studies indicate a negative correlation between high-density lipoprotein cholesterol (HDL-C) and the occurrence of diabetes, there are still some inconsistent findings. The contentious relationship between the two may be partially due to the undistingushement between the pre-diabetic and the normoglycemic participants in the previous studies, which may confound the association. This study aimed to investigate the relationship between the baseline HDL-C and incident type 2 diabetes mellitus (T2DM) in a Japanese cohort with normoglycemia or with prediabetes, respectively. Method In total, 10120 men (6791 with normoglycemia and 3329 with prediabetes) were enrolled from the NAGALA cohort from Jan 5th, 2004 to Dec 26th, 2015. Cox proportional hazards models were conducted to explore the association between baseline HDL-C levels and incident T2DM. A two-piecewise linear regression model was performed to evaluate the threshold effect of the baseline HDL-C concentration on T2DM incidence by using a smoothing function. Results During the median 5.95-year follow-up duration for participants with normoglycemia and 4.33-year follow-up period for prediabetes, 88 participantes with normoglycemia and 494 participantes with prediabetes developed T2DM. In the crude model and partly adjusted model, the risk of T2DM decreased significantly in both normoglycemia and prediabetes with increment in baseline HDL-C concentration. Howerver, the associations became nonsignificant after fully adjusting for possible confounders. Interestingly, in prediabetes, an L-shaped relationship between baseline HDL-C and risk of incident T2DM with a threshold HDL-C concentration of 32.4mg/dl was determined: the T2DM risk sharply decreased by 62% with the each 10mg/dl increment in HDL-C levels (HR = 0.377, 95%CI = 0.191–0.743) and the decline reaches a near plateau when the HDL-C concentration is higher than 32.4 mg/dl (HR = 0.986, 95%CI = 0.895–1.085). Conclusions Among a Japanese male population, an L-shape relationship between baseline HDL-C concentration and the risk of incident T2DM was explored in prediabetes, while no significant association was detected in men with normoglycemia.