Early Serum Clusterin Reduction is Associated with Weight Loss and Type 2 Diabetes Remission after Bariatric Surgery

OBJECTIVE: Clusterin is a newly identified adipokine associated with metabolic dysfunction, yet its postoperative dynamics and relationship to clinical outcomes after metabolic and bariatric surgery (MBS) remain unclear. This study aimed to investigate the changes of clusterin levels following MBS, evaluates its association with weight loss and type 2 diabetes (T2D) remission, and explore the underlying biological mechanisms. METHODS: In this 1-year retrospective cohort study, 75 patients with obesity and T2D (60% female, mean age 42 ± 12 years) undergoing MBS were enrolled. Metabolic outcomes included: (1) sufficient weight loss defined as total weight loss (TWL) ≥ 20%; (2) T2D remission as HbA1c < 5.7% and fasting glucose < 5.6 mmol/L without pharmacotherapy. Multivariable logistic regression and causal mediation analysis elucidated independent associations and potential mediating pathways. Clusterin levels were measured by enzyme-linked immunosorbent assay. RESULTS: <0.05), with rapid decline during the initial 6-month postoperative phase (Δ=-60.8 ± 129.8 ug/mL, P < 0.001) followed by stabilization. Multivariate analysis identified early clusterin reduction as an independent predictor of both sufficient weight loss (OR = 0.007, 95% CI 0.00-0.80, P = 0.04) and T2D remission (OR = 0.01, 95% CI 0.00-0.65, P = 0.036). Mediation analysis revealed that declines in weight, 2-hour postprandial insulin, and C-peptide partially mediated these associations. CONCLUSIONS: Clusterin levels showed a downward trend postoperative, and early-phase reductions predicting favorable metabolic outcomes. The association appears partially mediated by improved insulin resistance. These findings highlight the potential relevance of clusterin as a biomarker associated with metabolic clinical outcomes following MBS. KEY POINTS: • Early postoperative clusterin reduction is associated with weight loss and T2D remission. • The association is independent and partially mediated by improved insulin secretion. • Clusterin may serve as a potential biomarker for assessing metabolic surgery outcomes.