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

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 inconsistent findings may be partially due to the lack of distinction between participants with prediabetes and those with normoglycemia in previous studies. This study aimed to investigate the relationship between the baseline HDL-C and incident type 2 diabetes mellitus (T2DM) separately among Japanese participants with normoglycemia and those with prediabetes. In total, 10,120 men (6,791 with normoglycemia and 3,329 with prediabetes) were enrolled from the NAGALA cohort from Jan 5th, 2004 to Dec 26th, 2015. Cox proportional hazards models were used to explore the association between baseline HDL-C levels and incident T2DM. A two-piecewise linear regression model was used to evaluate the threshold effect of baseline HDL-C concentration on T2DM incidence by using a smoothing function. During a median follow-up of 5.95 years in participants with normoglycemia and 4.33-year in those with prediabetes, 88 normoglycemic participants and 494 prediabetic participants developed T2DM. In the crude model and partially adjusted model, the risk of T2DM decreased significantly with increasing baseline HDL-C in both groups; however, the associations became non-significant after full adjustment for potential confounders. In prediabetes, an L-shaped association between baseline HDL-C and incident T2DM was identified with a threshold HDL-C concentration of 32.4 mg/dL. Below the threshold, each 10 mg/dL increment in HDL-C was associated with a nearly 62% lower hazard of incident T2DM (HR = 0.384, 95% CI = 0.196–0.752), whereas no significant association was observed above the threshold (HR = 0.947, 95% CI = 0.862–1.042). In normoglycemia, no significant threshold effect was detected. Among Japanese men, an L-shaped relationship between baseline HDL-C concentration and the risk of incident T2DM was observed in those with prediabetes, while no significant association was detected in those with normoglycemia.