Differential plasma proteome analysis reveals key proteins associated with insulin resistance in acne vulgaris patients

Dr. Manjunath Hulmani

MBBS, MD, Skin Specialist and Cosmetologist

Dermacare Skin, Hair and Laser Clinic

Acne vulgaris (AV) is a chronic inflammatory disorder of the pilosebaceous unit and one of the most common dermatological conditions worldwide. Its multifactorial pathogenesis contributes to substantial physical and psychological burden. With a high incidence, AV affects about 95% of adolescent boys and 85% of adolescent girls, and nearly half of individuals continue to experience symptoms into adulthood.

Insulin resistance (IR) is a systemic condition involving multiple organs and insulin-regulated pathways. During puberty, physiological IR leads to hyperinsulinemia, which in turn elevates androgen levels. Both hyperinsulinemia and hyperandrogenemia contribute to acne development. Growing evidence has highlighted the relationship between AV and IR, with studies showing that androgen, insulin, and IGF-1 promote hyperkeratosis and lipid synthesis through multiple mechanisms, thereby triggering AV.

This study aimed to identify differential proteins linking AV and IR to support improved diagnostic and therapeutic strategies. Plasma proteomic profiling using LC-MS/MS was conducted on 90 AV patients (IR: n=40; non-IR: n=50) and 30 healthy controls (IR: n=11; non-IR: n=19). Differentially expressed proteins were analyzed through bioinformatics tools to pinpoint key molecules and pathways. Candidate proteins were selected based on their positive correlations with both AV severity and insulin levels.

In the AV with IR group, C4BPA was markedly upregulated, showed a strong positive correlation with insulin levels (Pearson’s R = 0.46, p=4.21E-6), and was enriched in complement agglutination cascade and B-cell-mediated immune pathways. In the overall AV group, C4BPA also correlated with disease severity (Pearson’s R=0.23, p=0.03; GAGS scores) and was enriched in complement and coagulation cascades as well as leukocyte-mediated immunity. These findings position C4BPA as a key molecule connecting IR and AV pathogenesis.

This study provides a valuable proteomic resource for understanding AV associated with insulin resistance and proposes a literature-supported mechanism in which insulin may worsen acne by influencing lipid metabolism and inflammatory pathways. The findings also suggest that C4BPA could serve as a key mediator in this process.

Reference: Rao Y, Lei Z, Chen S, et al. Differential plasma proteome analysis reveals key proteins associated with insulin resistance in acne vulgaris patients. Sci Rep. 2025;15(1):29342.