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Numerous studies have reported altered cytokine levels in type 1 diabetes (T1D) patients, yet findings remain inconsistent. In this pilot study, we tested the hypothesis that circulating immune markers exhibit sex-based differences in T1D, both prior to and after disease onset. We analyzed 47-48 cytokine, chemokine, and growth factor levels in two cohorts. To assess post-disease differences, we analyzed serum samples from 25 controls and 25 T1D patients. To examine pre-disease progression, we utilized samples from 21 control children and 16 T1D progressors, collected at age 5 years before disease onset. Across all T1D patients and controls, only macrophage colony-stimulating factor and interleukin (IL)-6 showed significant differences. However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Female T1D patients exhibited lower levels of inflammatory cytokines (tumor necrosis factor-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (macrophage inflammatory protein (MIP)-1α, regulated upon activation, normal T cell expressed and secreted, MIP-3) compared to female controls, differences that were not observed in males. Notably, IL-22 was lower in female T1D patients compared to female controls, whereas it was higher in male T1D patients compared to male controls. Male T1D patients showed elevated levels of growth factors (epidermal growth factor, platelet-derived growth factor-AB/BB) compared to male controls. In T1D progressors, growth-regulated alpha was lower compared to controls in both sexes. Multiple regression analysis further revealed associations between cytokine levels and factors such as age, BMI, and breastfeeding duration. Overall, our findings serve as a proof of concept, highlighting the importance of sex-specific differences in T1D pathogenesis. However, follow-up studies with larger sample sizes are needed to validate and generalize these results., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

While studies have reported altered levels of cytokines in type 1 diabetes (T1D) patients, the results are inconsistent, likely because of variable factors. This study tests the hypothesis that there are sex-based differences in cytokine levels in T1D, prior to and after disease onset. We analyzed 48 blood cytokine, chemokine, and growth factor levels using a multiplex assay. We found only two cytokines, M-CSF and IL-6, with significant differences between T1D patients (n=25) versus controls overall (n=25). However, we identified notable alterations when comparing sex-age-matched controls and T1D samples. Inflammatory cytokines (TNF-α, IL-6, IL-1a), Th2 cytokines (IL-4, IL-13), and chemokines (MIP-1α, RANTES, MIP-3) were lower in female T1D patients compared to female controls, but not in males. IL-22 was lower in female T1D patients compared to female controls, while it was higher in male T1D patients compared to male controls. In contrast, growth factors (EGF, PDGF-AB/BB) were higher in male T1D patients compared to male controls. In T1D progressors (children who developed the disease years after the sample collection, n=16-21), GROa was lower compared to controls in both sexes. Our findings underscore the importance of understanding sex-specific differences in T1D pathogenesis and their implications for developing personalized treatments.