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Research Article: Lipid metabolism-related inflammatory indices and diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study

Date Published: 2026-10-13

Abstract:
Improving the prognosis of diabetic kidney disease (DKD) requires early diagnosis and treatment. This study examined the associations of lipid metabolism-related inflammatory indices (LMIIs)—the platelet-, neutrophil-, monocyte-, and lymphocyte-to-high-density lipoprotein cholesterol ratios (PHR, NHR, MHR, and LHR, respectively)—with DKD in patients with type 2 diabetes mellitus (T2DM). A total of 3,468 T2DM patients were enrolled in this cross-sectional study. Logistic regression models were employed to assess the association between LMIIs and DKD. Restricted cubic splines (RCS) were used to evaluate nonlinear relationships, and threshold effect analysis identified inflection points. Subgroup analyses and sensitivity analyses, including inverse probability of treatment weighting, were performed to test the robustness of the findings. Mediation analysis was conducted to explore indirect associations through selected markers. The candidate mediator was not included as a conventional covariate in the corresponding model. Receiver operating characteristic (ROC) curves were used to evaluate the discriminative performance of models incorporating the four LMIIs. After multivariate adjustment, all four LMIIs showed significant positive associations with DKD ( P for overall < 0.05). RCS analysis revealed substantial nonlinear dose - response relationships for PHR, NHR, and MHR ( P for nonlinear = 0.009, 0.014, and 0.030, respectively), with inflection points at 2.65, 4.78, and 6.07, respectively. Subgroup analyses confirmed the robustness of these associations. However, lipid-lowering agent use significantly attenuated the NHR - DKD and MHR - DKD relationships ( P for interaction = 0.032 and 0.007, respectively). Sensitivity analyses yielded consistent results. TG and ALB showed statistically significant indirect associations in exploratory mediation analyses. ROC analysis showed that the model incorporating NHR had a slightly higher area under the curve (AUC) than those incorporating PHR and LHR ( P = 0.002 and 0.003, respectively). LMIIs were significantly associated with DKD and exhibited distinct nonlinear dose–response relationships with threshold effects. Lipid-lowering agent use attenuated the associations of NHR and MHR with DKD. NHR may provide modestly improved discrimination compared with PHR and LHR, while showing comparable performance to MHR. These findings highlight the potential relevance of lipid–inflammation interactions in DKD and warrant further prospective studies to clarify the underlying mechanisms and clinical implications.

Introduction:
Improving the prognosis of diabetic kidney disease (DKD) requires early diagnosis and treatment. This study examined the associations of lipid metabolism-related inflammatory indices (LMIIs)—the platelet-, neutrophil-, monocyte-, and lymphocyte-to-high-density lipoprotein cholesterol ratios (PHR, NHR, MHR, and LHR, respectively)—with DKD in patients with type 2 diabetes mellitus (T2DM).

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