Carbamylated HDL Independently Associated With Mortality Outcomes in T2D

Carbamylated high-density lipoprotein (HDL) is independently associated with mortality outcomes in people with type 2 diabetes, according to research published in Diabetes Care.

Researchers sought to evaluate the role of carbamylated HDL as a potential prognostic indicator of survival in a population of people with type 2 diabetes and well-preserved kidney function, as well as the association with mortality outcomes.

In total, 1,679 people with type 2 diabetes were recruited; those receiving renal replacement therapy or those missing follow-up data or baseline samples were excluded, resulting in a cohort of 1517 patients. At baseline, 20.5% of patients had stage 1 chronic kidney disease, 54.5% had stage 2, 21% had stage 3, 3.6% had stage 4, and 0.4% had stage 5. Just over 300 patients (n=301) died during follow-up and were excluded from the analysis.

Median follow-up duration for this study was 14 years (interquartile range, 9.5-17.4 years) with a mortality rate of 14.5 per 1,000 person-years. Deaths resulted from cardiovascular causes (31%), renal causes (21%), malignancy (20%), and infection (19%), with the remaining deaths due to trauma, chronic lung disease, or uncertain etiologies. Patients who died were generally older, but no significant difference in diabetes duration was noted.

Similar plasma HDL-C concentrations were noted in both patient groups; plasma carbamylated HDL was elevated in patients who died (46.1±17.8 ug/mL vs 32.9±10.7 ug/mL; P <.01). This difference remained significant after adjustment for age and sex. Investigators performed a Kaplan-Meier analysis and stratified patients into 4 quartiles based on baseline plasma carbamylated HDL; a graded association between increasing quartiles and all-cause mortality was noted.

A multivariable Cox regression analysis was also performed, adjusting for potential confounding factors including baseline clinical characteristics, renal function, and traditional cardiovascular risk factors. Results of a crude model found an unadjusted hazard ratio [HR] per 1 standard deviation change in plasma carbamylated HDL of 1.72. In fully adjusted models, the association between plasma carbamylated HDL and all-cause mortality remained significant.

In further analyses of whether plasma carbamylated HDL was associated with cause-specific mortality outcomes, researchers found an independent association with cardiovascular-, renal-, infection-, and cancer-related deaths (HR, 1.36, 1.37, 1.53, and 1.39, respectively). Adjustments for HDL-C did not change the results of any analysis.

Finally, ROC analysis results demonstrated that for all-cause mortality, the C index for the model including traditional risk factors (diabetes duration, HbA1c, estimated glomerular filtration rate, baseline cardiovascular disease, renin-angiotensin system blockers, and lipid-lowering therapy) was 0.78. The model’s predictive power improved with the addition of plasma carbamylated HDL (C index increase to 0.80).

Study limitations include the possible of residual unmeasured confounding factors, the small number of outcome events for cause-specific deaths, and the exploratory nature of the analyses.

“Carbamylation of HDL renders HDL dysfunctional, and carbamylated HDL is independently associated with mortality outcomes in patients with type 2 diabetes,” researchers concluded. “Additional mechanistic studies are warranted to determine whether carbamylated HDL is simply a disease biomarker or also a mediator of adverse mortality outcomes.”

Reference

Lui DTW, Cheung C-L, Lee ACH, Wong Y, Shiu SWM, Tan KCB. Carbamylated HDL and and mortality outcomes in type 2 diabetes. Diabetes Care. 2021;44(3):804-809.