Interleukin-6-Related Inflammatory Burden in Type 1 Diabetes: Evidence for Elevation with Suboptimal Glycemic Control

<b>Background/Objectives</b>: Inflammation is a hallmark of diabetes, with interleukin-6 (IL-6) emerging as a key mediator linking immune activation with metabolic regulation. Although IL-6 has been studied in both type 1 (T1D) and type 2 diabetes (T2D), its relationship with glycemic control across diabetes subtypes remains unexplored. <b>Methods</b>: We conducted a cross-sectional pilot study including 82 participants divided into the following subgroups: healthy controls (<i>n</i> = 14), individuals with T1D [<i>n</i> = 11 with glycated hemoglobin (HbA1c) < 7%; <i>n</i> = 11 with HbA1c ≥ 7%] and T2D (<i>n</i> = 21 with HbA1c < 7%; <i>n</i> = 25 with HbA1c ≥ 7%). Demographic, anthropometric, and laboratory parameters were collected. Group comparisons were performed, adjusted for age and body mass index (BMI) to account for significant demographic differences between groups. Correlations between IL-6, high-sensitivity C-reactive protein (hs-CRP), ferritin, and presepsin were evaluated using Spearman's rank correlation. <b>Results</b>: IL-6 levels were approximately four-fold higher in T1D individuals with HbA1c ≥ 7% compared with controls [fold-change 4.06 (95% CI: 1.36-12.1), <i>p</i> = 0.013], with optimally managed T1D showing a non-significant trend (<i>p</i> = 0.079). No significant differences were observed in T2D groups. Advancing age demonstrated a borderline association with IL-6 (<i>p</i> = 0.068), whereas BMI was not significantly related. IL-6 correlated positively with hs-CRP (ρ = 0.463, <i>p</i> < 0.001), but not with ferritin or presepsin. <b>Conclusions</b>: IL-6 concentrations were significantly elevated in individuals with suboptimally managed T1D compared with controls, independent of age and BMI, suggesting that poor metabolic control amplifies systemic inflammation in autoimmune diabetes. These findings support IL-6 as a biomarker of inflammatory burden in T1D and provide a rationale for larger, longitudinal studies to determine its clinical utility.