The Metabolic-Microvascular Axis in Systemic Sclerosis: Decoding the Potential Influence of Insulin Resistance on Nailfold Capillaroscopic Findings

Insulin resistance (IR) exerts negative effects on vascular homeostasis and endothelial functionality. Its relationship with microvascular damage in systemic sclerosis (SSc) is lacking. This study aimed to investigate the association between IR and nailfold videocapillaroscopy (NVC) abnormalities in SSc.

We conducted a cross-sectional study including patients diagnosed with SSc according to 2013 American College Rheumatology/European Alliance of Associations for Rheumatology criteria. IR was assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), with a cut-off ≥ 2.5. NVC findings, including qualitative categorization (early, active, and late pattern) and semiquantitative assessment, were compared between two groups based on the presence of IR. Chi-square, Fischer exact, T-student, and Mann-Whitney U tests were used for univariable analysis. p for trend was calculated for semiquantitative grading. Multivariable logistic regression analysis was performed to identify factors independently associated with HOMA-IR ≥ 2.5.

A total of 124 SSc patients were recruited. Thirty-seven patients (29.8%) had HOMA-IR ≥ 2.5. Compared with patients with HOMA-IR < 2.5 (87 patients, 71.2%), IR patients had a higher prevalence of dyslipidemia and higher body mass index (BMI). NVC analysis revealed that the late pattern was more frequent among patients with IR (p = 0.007), while the early pattern was in patients without IR (p = 0.0037). Vascular bed disorganization and neoangiogenesis/ramifications were more frequently observed in the IR group (0.017 and 0.02, respectively). Multivariable analysis revealed that the late pattern was independently associated with IR (OR 1.09, 95% CI 1.001-1.19; p = 0.048), after correction for age and BMI.

IR is associated with microvascular damage in SSc, suggesting a conceptual link between metabolic dysfunction and microangiopathy.