Serum alpha-1-microglobulin as a predictor of multiple complications in type 2 diabetes mellitus patients

BACKGROUND Poor glycaemic control in patients with type 2 diabetes mellitus (T2DM) is often accompanied by multiple complications, including diabetic nephropathy (DN), diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and cardiac structural abnormality left ventricular hypertrophy (LVH). Early identification of high-risk populations for these complications and the implementation of intervention measures are crucial for improving patient outcomes. Serum alpha-1-microglobulin (α1-MG), a multifunctional protein synthesized by the liver and lymphocytes, has been considered a potential biomarker of diabetes-related diseases in recent years. AIM To investigate the associations of serum α1-MG with DN, DR, DPN, and LVH in T2DM patients and its predictive value. METHODS This retrospective study included 5045 T2DM patients. The study participants were stratified into quartiles according to their serum α1-MG levels. Multivariate logistic regression, restricted cubic spline, and explainable machine learning models were employed for risk assessment and feature importance evaluation. RESULTS Increased α1-MG levels were observed in patients with DN, DR, DPN, and LVH (all P < 0.001). Multivariate logistic regression revealed that each standard deviation increase in α1-MG was associated with an 84% increase in DN risk (OR: 1.84, 95%CI: 1.62-2.10, P < 0.001), a 17% increase in DR risk (OR: 1.17, 95%CI: 1.07-1.28, P < 0.001), a 14% increase in DPN risk (OR: 1.14, 95%CI: 1.03-1.27, P = 0.014), and a 28% increase in LVH risk (OR: 1.28, 95%CI: 1.18-1.38, P < 0.001). Subgroup analyses and machine learning confirmed the associations of elevated α1-MG with these complications in T2DM patients. CONCLUSION Elevated serum α1-MG levels were independently associated with increased risks of DN, DR, DPN, and LVH in T2DM patients, suggesting its potential as a predictive biomarker.