Oxidised lipoproteins and the risk of type 2 diabetes mellitus: A 5‐year cohort study on β‐cell dysfunction and prediabetes progression

AIMS: Oxidised lipoproteins-including oxidised high-density lipoprotein cholesterol (ox-HDL-C), oxidised low-density lipoprotein cholesterol (ox-LDL-C) and oxidised lipoprotein(a) [ox-Lp(a)]-are emerging biomarkers of oxidative stress and vascular inflammation. However, their roles in glycometabolic disorders and the progression from prediabetes to type 2 diabetes mellitus (T2DM) remain poorly defined. To prospectively assess the associations between plasma ox-HDL-C, ox-LDL-C and ox-Lp(a) levels and the future risk of T2DM among individuals with prediabetes. MATERIALS AND METHODS: This multi-centre, prospective cohort study enrolled 3056 participants, including 1521 individuals with prediabetes who were followed for 5 years. Baseline levels of ox-HDL-C, ox-LDL-C and ox-Lp(a) were quantified using ELISA. Glycaemic indices, insulin resistance markers and β-cell function were assessed. Associations with incident T2DM were evaluated using logistic regression, Cox proportional hazards models and restricted cubic spline analyses. RESULTS: Elevated baseline levels of ox-HDL-C, ox-LDL-C and ox-Lp(a) were independently associated with increased odds and hazard ratios for progression from prediabetes to T2DM. These associations were dose-dependent and remained significant across sex-specific subgroups. Additionally, oxidised lipoproteins correlated positively with FBG, HbA1c and HOMA-IR, and negatively with HOMA-β and HOMA-IS, suggesting a relationship with β-cell dysfunction and insulin resistance. CONCLUSIONS: Ox-HDL-C, ox-LDL-C and ox-Lp(a) are independent, dose-dependent predictors of T2DM development in individuals with prediabetes. Their close association with impaired β-cell function highlights their potential utility in early risk stratification and targeted prevention strategies for T2DM.