High-density lipoprotein cholesterol-related inflammatory markers as indicators of diabetic kidney disease in diabetes with sleep disturbance

This study aimed to evaluate the association between high-density lipoprotein cholesterol (HDL-C)-related inflammatory markers and diabetic kidney disease (DKD) in participants with diabetes and sleep disturbance. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2018. The NHANES dataset contains 4,185 participants, but the principal analysis concerns 763 participants with sleep disturbance, including 312 with DKD. DKD was defined as urinary albumin-to-creatinine ratio (uACR) ≥ 30 mg/g or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². HDL-C-related inflammatory markers, including uric acid-to-HDL-C ratio (UHR), monocyte-to-HDL-C ratio (MHR), lymphocyte-to-HDL-C ratio (LHR), neutrophil-to-HDL-C ratio (NHR), and platelet-to-HDL-C ratio (PHR), were calculated from routine laboratory parameters. Multivariable logistic regression models were used to evaluate the associations between these markers and DKD among participants with sleep disturbance. Restricted cubic spline (RCS) analysis, subgroup analysis, and receiver operating characteristic (ROC) curve analysis were further performed. We further externally validate the main findings using an independent cross-sectional dataset from the 2015 wave of CHARLS (China Health and Retirement Longitudinal Study). The prevalence of DKD was significantly higher in participants with sleep disturbance than in those without sleep disturbance. Participants with sleep disturbance also showed elevated levels of HDL-C-related inflammatory markers. In participants with sleep disturbance, UHR and NHR showed a positive association with DKD. RCS analysis indicated linear positive associations of UHR and NHR with diabetic kidney disease risk. ROC curve analysis indicated that UHR and NHR had better discriminatory ability for DKD than other HDL-C-related inflammatory markers, although the overall discrimination was limited (AUC = 0.58, 95% CI: 0.57–0.60 for UHR; AUC = 0.56, 95% CI: 0.54–0.57 for NHR). In the CHARLS validation dataset, higher UHR was also significantly associated with DKD. In patients with diabetes and sleep disturbance, elevated NHR and UHR were independently associated with a higher prevalence of DKD in NHANES. External replication in an independent cross-sectional dataset from the 2015 wave of CHARLS further supported the association between UHR and DKD, suggesting that this finding may be relatively robust across datasets. These readily accessible biomarkers may facilitate DKD risk assessment; however, whether they have clinical utility for risk stratification remains to be determined in future prospective studies. Not applicable.