Commentary on α-1-microglobulin as a predictor of diabetic complications

Abstract

This letter comments on the study by Ge et al. Serum α1-microglobulin (α1-MG) was reported to be associated with diabetic nephropathy, retinopathy, peripheral neuropathy, and left ventricular hypertrophy. The letter further highlights the need for multicenter validation and evaluation of clinical applicability to clarify the role of α1-MG in diabetes management.

Key Words: α1-microglobulin; Type 2 diabetes mellitus; Machine learning models; Commentary

Core Tip: This letter comments on the recent study regarding serum α1-microglobulin (α1-MG) as a predictor of multiple complications in type 2 diabetes mellitus. The letter underscores the importance of α1-MG as a potential biomarker linking renal, retinal, neural, and cardiac complications, and highlights the need for multi-center validation and cost-effectiveness evaluation before clinical adoption.

TO THE EDITOR

We read with interest the article by Ge et al[1] entitled “Serum alpha-1-microglobulin as a predictor of multiple complications in type 2 diabetes mellitus patients”. The authors reported that elevated serum α1-microglobulin (α1-MG) was independently associated with diabetic nephropathy, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and left ventricular hypertrophy (LVH) in a large cohort of 5045 patients with type 2 diabetes (T2D). Restricted cubic spline analysis revealed a dose-response pattern with a threshold around 25.85 mg/L. These findings broaden our understanding of α1-MG as a potential biomarker across microvascular and cardiac complications in T2D.

Previous studies have mainly focused on renal outcomes. For example, Pan et al[2] showed that the urinary α1-MG/creatinine ratio, when combined with plasma fibrinogen, improved the prediction of diabetic kidney disease. Similarly, Hong et al[3] demonstrated that urinary α1-MG is a sensitive marker of nephropathy in Asian patients with T2D. Ge et al[1] extend this evidence by highlighting the role of serum α1-MG not only in nephropathy but also in DR, DPN, and LVH.

Several points deserve further exploration. Although Ge et al[1] demonstrated robust associations, whether α1-MG provides incremental predictive value beyond eGFR and albuminuria remains to be established in future studies. Reporting calibration, Brier scores, and decision-curve analysis[4] would provide evidence for incremental clinical utility. Calibration assesses the agreement between predicted and observed outcomes, whereas decision-curve analysis quantifies the net clinical benefit of applying a biomarker such as α1-MG in clinical decision-making, thus demonstrating its value beyond statistical significance. Moreover, the proposed threshold (approximately 25.85 mg/L) requires external validation, particularly in older T2D patients with multimorbidity and frailty, where risk stratification may be especially valuable.

In conclusion, Ge et al[1] provides timely and valuable evidence that serum α1-MG may serve as a cross-complication biomarker in T2D. By linking a renal tubular marker to microvascular and cardiac outcomes, this study opens new avenues for risk stratification and prevention of T2D complications. However, the clinical adoption of α1-MG should be further supported by multi-center validation and cost-effectiveness evaluation to ensure its feasibility and practical utility in diabetes management.