Metabolic Dysfunction and Acne Severity: Mechanisms and Clinical Implications

Abstract

Background:
Acne vulgaris is one of the most common dermatological disorders worldwide and remains a frequent cause of clinical consultation in both adolescents and adults. Although traditionally understood as a disease of the pilosebaceous unit driven by androgen activity, follicular hyperkeratinization, sebaceous gland dysfunction, microbial imbalance, and inflammation, increasing evidence suggests that systemic metabolic disturbances may also contribute to disease severity and persistence [1–6]. In particular, insulin resistance, insulin-like growth factor-1 (IGF-1) signaling, adiposity, dyslipidemia, and hyperandrogenic states have emerged as potentially relevant modifiers of acne pathophysiology [7–11].

Objective:
To synthesize and critically evaluate current evidence linking acne severity with multiple domains of metabolic dysfunction, including insulin resistance, IGF-1 signaling, obesity-related pathways, lipid abnormalities, and endocrine dysregulation, and to assess their clinical relevance for dermatology practice [12–19].

Methods:
A systematized review with narrative synthesis was conducted using PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library. Studies published between January 2000 and March 2026 were screened using predefined eligibility criteria. Observational, interventional, and mechanistic clinical studies evaluating associations between acne and metabolic parameters were considered. Data were extracted on study design, population characteristics, acne severity measures, metabolic exposures, and key outcomes. Methodological quality was appraised using appropriate tools, and evidence was synthesized across predefined metabolic domains rather than pooled quantitatively because of substantial heterogeneity in study designs, populations, and definitions [12–19].

Results:
Current evidence suggests an association between acne severity and several forms of metabolic dysfunction, with the most consistent findings observed for insulin resistance and related glucose metabolism abnormalities [12–19]. Mechanistic studies support the role of IGF-1 activation, mammalian target of rapamycin complex 1 (mTORC1) signaling, and reduced sex hormone-binding globulin in increasing androgen bioavailability, sebaceous gland activity, and inflammatory responses [20–27]. Obesity and altered body composition may further modulate acne through adipokine imbalance and chronic low-grade inflammation, although findings are not consistent across all studies [28–32]. Dyslipidemia has also been reported in acne populations, but results remain heterogeneous and are influenced by methodological variability and potential treatment-related confounding [33–37]. In contrast, evidence linking acne directly to formally defined metabolic syndrome is less consistent than evidence linking acne to its individual metabolic components [7–11,44–47].

Conclusion:
Acne vulgaris should not be reclassified as a metabolic disorder; however, available evidence indicates that acne severity may be influenced by broader systemic metabolic and endocrine processes, particularly insulin resistance and IGF-1–mediated pathways [12–27]. The relationship with formal metabolic syndrome remains heterogeneous and insufficiently established [7,14,44–47]. These findings support a more integrated dermatological approach in selected high-risk patients, especially those with severe, persistent, treatment-resistant, or hormonally influenced acne. Further longitudinal and interventional studies are needed to clarify causality and define the role of targeted metabolic evaluation and intervention in acne management [12,26,38,44–47]. These findings highlight the importance of considering metabolic factors in selected patients with moderate-to-severe or treatment-resistant acne.

Keywords: Acne vulgaris; Insulin resistance; Metabolic dysfunction; IGF-1; mTOR; Dyslipidemia; Obesity; Polycystic ovary syndrome.