HDL cholesterol and clinical outcomes in diabetes mellitus

Lay Summary The aim of this study is to clarify whether fasting plasma glucose modifies the U-shaped association between HDL cholesterol and clinical outcomes. Key findings The U-shaped association between HDL cholesterol and clinical outcomes (including myocardial infarction, stroke, and death) was amplified with worsening glucose tolerance, suggesting a potential interaction between HDL cholesterol levels and glycaemic status on clinical outcomes. Aims HDL cholesterol (HDL-C) has been thought to protect against cardiovascular disease (CVD), whereas a U-shaped association of both low and extremely high HDL-C with a high mortality risk has been increasingly reported in recent years. However, whether this U-shaped association is universal regardless of the individual's clinical background, including lifestyle diseases, remains unclear. We examined whether fasting plasma glucose modifies the U-shaped association between the HDL-C level and clinical outcomes. Methods and results This retrospective observational cohort study analysed data from the JMDC Claims Database between 2005 and 2021 for 3 282 389 participants without a history of CVD. The median age was 44 years (IQR, 36-51), and 1 878 164 participants (57.2%) were men. The median HDL-C level was 62 (IQR 52-74) mg/dL. The study participants were categorized according to fasting plasma glucose (FPG) levels (<100 mg/dL, 100-125 mg/dL, and >= 126 mg/dL). The primary endpoint was composite CVD outcome, consisting of myocardial infarction, stroke, and all-cause death. During a mean follow-up period of 1181 +/- 932 days, 35 233 composite CVD events were recorded. The association between low HDL-C and CVD risk increased with the FPG level, and the relationship of high HDL-C with CV outcome was prominent only in people with diabetes mellitus. A similar relationship was observed in the individual subgroups and in each CV outcome. Conclusion The U-shaped association between HDL-C and clinical outcomes was amplified with worsening glucose tolerance, suggesting a potential interaction between HDL-C levels and glycaemic status on clinical outcomes.

Automated summary

The aim of this study was to investigate the association between fasting plasma glucose, HDL cholesterol levels, and clinical outcomes. The findings suggest that there is a U-shaped association between HDL cholesterol and clinical outcomes, and this association is amplified with worsening glucose tolerance.