Association of HDL2b with chronic kidney disease in type 2 diabetes mellitus populations

Background and purpose: Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM). High-density lipoprotein cholesterol (HDL-C) has traditionally been considered renoprotective, yet growing evidence suggests that HDL subclasses may differ in biological function. This study aimed to investigate the association between HDL subclasses, particularly HDL2b, and chronic kidney disease (CKD) in Chinese adults with T2DM. Methods: In this cross-sectional study, patients with T2DM were enrolled. CKD was defined as urinary albumin-to-creatinine ratio (UACR) ≥3.0 mg/mmol and/or estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m². HDL subclasses were measured using capillary electrophoresis-based microfluidics. Participants were categorized into quartiles of HDL-C, HDL2b, and HDL3. Multivariable logistic regression models were constructed with progressive adjustment for anthropometric indices, hypertension, insulin resistance (HOMA-IR), and inflammatory markers. Results: Among 481 patients with T2DM, 136 (28.3%) had CKD. Patients with CKD exhibited significantly lower HDL2b levels (P = 0.001), together with greater insulin resistance and systemic inflammation (all P<0.05). HDL2b showed stronger inverse correlations than total HDL-C with adiposity, glycemic indices, insulin resistance, and inflammatory markers (all P<0.05). In multivariable logistic regression, higher HDL2b was independently associated with a lower risk of CKD. Compared with the lowest quartile, the third and fourth quartiles were associated with reduced odds of CKD (Q3: OR = 0.425, 95% CI 0.220-0.821, P = 0.012; Q4: OR = 0.367, 95% CI 0.188-0.717, P = 0.001). The inverse association between HDL2b and CKD was stronger in participants with higher insulin resistance (P for interaction=0.044). Conclusion: Higher HDL2b, but not total HDL-C or HDL3, is independently associated with lower risk of CKD in T2DM. HDL2b may serve as a sensitive biomarker for early renal risk stratification.