Introduction
Dyslipidemia is a major risk factor for cardiovascular disease in type 2 diabetes mellitus (T2DM), but its association with kidney disease progression remains incompletely defined. Although low high-density lipoprotein cholesterol (HDL-C) has been linked to diabetic nephropathy, evidence regarding hard kidney outcomes is limited. We examined the associations between HDL-C and kidney events in patients with T2DM, in comparison with other lipid parameters.
Research design and methods
A total of 1,033 patients with T2DM from the Fukushima Cohort Study were included. Participants were followed for kidney events, defined as a ≥50% decrease in estimated glomerular filtration rate (eGFR) or onset of kidney failure requiring kidney replacement therapy, and all-cause mortality over a median follow-up period of 5.3 years. Lipid parameters HDL-C, triglycerides (TG), low-density lipoprotein cholesterol, non-HDL-C, and TG/HDL-C ratio were categorized into quartiles and evaluated using Cox proportional hazards models, adjusted for age, sex, smoking history, history of cardiovascular disease, body mass index, systolic blood pressure, eGFR, hemoglobin A1c, and proteinuria.
Results
The median patient age was 66 years, 56% were men, and the median eGFR was 68.6 mL/min/1.73 m2. After multivariable adjustment, patients in the lowest HDL-C quartile (<42 mg/dL) had significantly higher risks of kidney events (adjusted HR 2.61, 95% CI 1.32 to 5.14) and all-cause mortality (adjusted HR 2.27, 95% CI 1.16 to 4.42) than the reference group (HDL-C 49–58 mg/dL). A U-shaped association was observed between HDL-C and all-cause mortality. Subgroup and sensitivity analyses were consistent. No significant associations were observed for other lipid parameters with either kidney events or mortality.
Conclusions
Low HDL-C levels were independently associated with kidney events and all-cause mortality in patients with T2DM. Future studies are warranted to clarify whether interventions targeting HDL-C can improve kidney disease progression in this high-risk population.
Trial registration number
UMIN000040848.
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