Recent research focused on identifying mechanisms explaining the observed heterogeneity of type 1 diabetes (T1D) in age at onset, residual β-cell function and rate of disease progression. Mechanisms include changes in both the immune system and β-cells, leading to the loss of tissue-specific immune tolerance and disease onset. Interleukin-8 (IL-8; CXCL8) is a pro-inflammatory chemokine released by macrophages, endothelial, epithelial and airway smooth muscle cells playing a major role in the innate immune response. Macrophages release IL-8 at the site of an injury where they recruit and activate neutrophils by interacting with the IL-8 receptors CXCR1 and CXCR2. An increase in circulating IL-8 has been shown in several autoimmune disorders. IL-8 levels, but not IL-6 or TNF-α, are elevated in adolescents with T1D, and also associated with insulin resistance, suggesting a role for IL-8 beyond acute inflammation in this setting. In vitro experiments revealed that IL-8 transcription is induced by hyperglycaemia. In the present study newly diagnosed T1D patients within the first year of disease onset (mean age 16.2 ± 7.6 yrs and % HbA1c of 10.7 ± 2.7) (N=42) were studied. Clinical and laboratory features included age, gender, body mass index (BMI), disease duration, HbA1c, and C-peptide. Serum IL-8 and myeloperoxidase (MPO) were measured with commercial enzyme-linked Immunosorbent assays. When compared to normal subjects, T1D patients showed a significantly higher IL-8 values (median [IQR] 112.0 [64.74-311.8] vs 43.05 [30.94-49.70], p-value= 0.002, respectively). Furthermore, T1D patients showed a significantly higher MPO levels than controls (median [IQR], 95327 [55718 - 168974] vs 42729 [24147 - 95327], p-value= 0.0349, respectively). This study shows for the first time that IL-8 and MPO are elevated in patients with recent onset T1D compared to normal subjects. There is also a trend for a positive correlation between IL-8 and HbA1c levels suggesting that elevated IL-8 values are associated with poor metabolic control. Disclosure G.Alhamar: None. S.Fallucca: Consultant; Dompé. S.Pieralice: None. L.Valente: None. P.Pozzilli: None.

Background: Coronavirus (COVID-19) disease portends a poor prognosis in patients with type 1 diabetes (T1D) . As a consequence, the booster dose of Covid-vaccination should be prioritized in these patients. Nonetheless, concerns exist about vaccine-induced dysglycemia. Objectives: Aim of this study was to assess the short-term effects of booster dose of Covid-vaccination on glycaemic control assessed by flash glucose monitoring (FGM) in people with T1D. Methods: In this observational cross-sectional study we investigated changes in daily insulin requirement (IR) and glycaemic control between 7 days before and 7 days after the third dose of vaccination with BioNTech Pfizer among 30 individuals with T1D on multiple daily insulin injections wearing a flash glucose monitoring (FGM) device. The following parameters of glycaemic variability were analysed: mean glucose, time in range (TIR) , time above range (TAR) , time below range (TBR) and coefficient of variation (CV) . Results: No significant differences were found for mean glycemia, TIR, TAR and TBR over the course of the vaccination from 7 days prior to receiving the third-dose vaccination until 7 days after. Nonetheless, CV and IR were significantly higher (CV, p-value = 0.001; IR, p-value = 0.05) in the week after the vaccination compared to the week earlier. The median value of CV was 35.5% [33-37] before and 36.9% [34-39] after the booster dose, whereas the median value of IR changed from 0.55 UI/Kg/day to 0.61 UI/Kg/day. Conclusions: Our study suggests that the booster dose of Covid-vaccination impact on glycaemic variability and insulin requirement in people with T1D, probably due to the pro-inflammatory cytokines and immune responses. While this observation should be investigated in larger studies, potential glycaemic aberrations in response to Covid-immunization should be considered by health care professionals and glucose monitoring intensified within the days around the vaccination. Disclosure S.Pieralice: None. L.Monte: None. G.Defeudis: None. G.Tabacco: None. N.Napoli: Advisory Panel; Novo Nordisk, Consultant; Lilly Diabetes. P.Pozzilli: Advisory Panel; Dompé, Consultant; Abbott, Speaker’s Bureau; Dompé, Lilly Diabetes, Medtronic, Sanofi.

There has been no meta-analysis that addressed the essential issue of efficacy of immunomodulatory agents on HbA1c in patients with recent onset type 1 diabetes (T1D). The aim of this study was to conduct a systematic review and meta-analysis to estimate the treatment effect of different immunotherapeutic strategies vs. placebo on HbA1c in subjects with T1D over the first 2 years of disease. We searched PubMed and Clinicaltrials.gov from 1990 until November 2022 to identify randomized clinical trials (RCTs) and observational investigations that compared the efficacy of immunomodulatory agents in adult and children with recent onset T1D. The study included 35 trials with a total of 2987 participants, 2086 in the treatment groups and 901 in the control groups. We extracted information about year of publication, study and exposure duration, immunotherapy type, no. patients, age, sex, weight, and BMI. HbA1c was evaluated at baseline, and at 3, 6, 9, 12 and 24 months. Funnel plots with confidence regions were used to explore small-study and publication biases. A random-effects model to pool effect sizes Knapp-Hartung adjustments was used to calculate confidence intervals. The evaluation outlined a significantly higher HbA1c in the treatment group at baseline (MD = 0.26 %, 95% confidence interval (CI) 0.0025 to 0.51). Heterogeneity was detected (I2 = 67%; p<0.01; prediction interval -0.71 to 1.23). Small trials with higher HbA1c in the treatment group seem to be underrepresented, however, most of the studies provided non-significant results. In analysis at 12 months (12 trials) results showed a significantly higher HbA1c in the treatment group (MD = 0.13 %, 95% confidence interval (CI) 0.09 to 0.16). This result is almost driven by one study. Results of the metanalysis indicate that overall, in the first 2 years of the disease and irrespective of the immunointervention agent tested, no effect on HbA1c levels could be detected vs. placebo. A few exceptions were observed in the data analysis with some agents. Disclosure P.Pozzilli: None. S.Fallucca: Consultant; Dompé. S.Pieralice: None. M.Marelli: Employee; Dompé. L.Mancini: None.