Circulating levels of chemokines and cardiometabolic profile in adults with type 1 diabetes: an observational study

Aims – People with type 1 diabetes (T1D) face an increased cardiovascular (CV) risk compared to the general population. While increasing evidence supports the role for chemokines, including RANTES and CXCL1, in the pathogenesis of T1D, their relationship with CV risk profile remains debated. We aimed to stratify a cohort of adults with T1D according to their cardiometabolic profile and investigate the association between these chemokines and established risk determinants. Methods – We conducted an observational study enrolling adults of both sexes with type 1 diabetes on stable intensive insulin therapy. Participants were stratified based on three key cardio-metabolic determinants: 1) 10-years cardiovascular risk calculated by the Steno Type 1 Risk Engine (ST1RE), 2) insulin resistance defined by an estimated Glucose Disposal Rate (eGDR) < 8 and 3) body mass index (BMI) ≥ 25 kg/m2. Circulating levels of RANTES and CXCL1 were quantified using enzyme-linked immunosorbent assays (ELISA) kits. Results – We included 67 adults, with median age of 28 years and diabetes duration of 17 years. Prevalence of insulin resistance and overweight/obesity was 31.3% and 44.8%, respectively. RANTES levels were significantly higher in overweight/obese participants compared with normal-weight peers (overweight/obese vs normal weight, 4010.4 vs 2684.2, pg/ml, P=0.044). Conversely, CXCL1 levels were significantly lower in insulin-resistant individuals (eGDR < 8 vs eGDR ≥ 8, 195.1 vs 319.0, pg/ml, P=0.048). Furthermore, CXCL1 levels were higher in people with shorter diabetes duration (<17 years) compared to those with longer diabetes duration (P=0.007). Regression analysis confirmed an inverse association between CXCL1 levels and diabetes duration (β=-0.320, P=0.008), while no other significant association was found between chemokines and the determinants of cardio-metabolic profile. Conclusions – In adults with T1D, the circulating levels of RANTES reflect obesity or overweight status, whereas CXCL1 levels are inversely associated with disease duration. Neither chemokine correlated with the estimated cardiovascular risk score (ST1RE) or insulin resistance in regression models, suggesting that these inflammatory markers may not reflect the current cardio-metabolic burden in young adults with established disease and low-to-moderate risk.