HDL cholesterol and clinical outcomes in diabetes mellitus

Area of Science:

• Cardiovascular Medicine
• Metabolic Disorders
• Epidemiology

Background:

• High-density lipoprotein cholesterol (HDL-C) is traditionally viewed as protective against cardiovascular disease (CVD).
• Recent studies suggest a U-shaped association between HDL-C levels and mortality risk, indicating increased risk at both low and very high levels.
• The influence of glycemic status on this U-shaped association remains unclear.

Purpose of the Study:

• To investigate whether fasting plasma glucose (FPG) modifies the U-shaped association between HDL-C levels and clinical outcomes.
• To determine if the relationship between HDL-C and cardiovascular events differs across varying levels of glucose tolerance.

Main Methods:

• Retrospective observational cohort study utilizing the JMDC Claims Database (2005-2021).
• Analysis of 3,282,389 participants without prior CVD, categorized by FPG levels (<100, 100-125, ≥126 mg/dL).
• Primary endpoint: composite CVD outcome (myocardial infarction, stroke, all-cause death).

Main Results:

• The association between low HDL-C and increased CVD risk was more pronounced with higher FPG levels.
• The protective effect of high HDL-C against cardiovascular outcomes was diminished or absent in individuals with diabetes mellitus.
• These relationships were consistent across individual CVD outcomes and subgroups.

Conclusions:

• The U-shaped association between HDL-C and clinical outcomes is amplified by impaired glucose tolerance.
• Glycemic status significantly interacts with HDL-C levels in determining cardiovascular risk.
• These findings highlight the complex interplay between lipid metabolism and glucose control in CVD pathogenesis.