The role of chemokines in type 1 diabetes-associated neuropathy

Introduction: To investigate whether circulating chemokines contribute to the development of diabetic peripheral neuropathy (DPN) in patients with type 1 diabetes (T1D). Methods: Fifty-two patients with childhood-onset T1D (mean age 28 +/- 4 yrs.; diabetes duration 19.5 +/- 5.5 yrs.) and 19 control subjects (mean age 26.5 +/- 4.5 yrs.) were included in a cross-sectional analysis of this long-term longitudinal cohort study. A subgroup of 24 patients was followed prospectively for a further 10 yrs. Plasma levels of Th1-(CXCL9, CXCL10 and CXCL11), Th2-(CCL17 and CCL22) and Th17-associated (CXCL8 and CCL20) chemokines were assessed in all subjects. Additionally, the TID patients underwent clinical examination and electroneurography. Results: The frequency of neuropathy was 21% (11/52). Higher levels of CXCL9 levels were found in patients with DPN compared with control subjects (p = .019); by contrast, no difference between patients without DPN and control subjects was seen after adjustment for multiple comparisons. In patients with DPN, CXCL10 correlated negatively with suralis MCV and suralis SNAP (rho -0.966, p < .001 and rho -0.738, p <.001, respectively) and was positively correlated with the vibration perception threshold (rho 0.639, p = .034), while CXCL8 correlated negatively with the cold perception threshold (rho -0.645, p = .032). The frequency of neuropathy increased to 54% (13/24) in the subgroup of 23 TID patients, followed by an additional 10 yrs. Conclusions: Changes in Th1-and Th17-associated chemokines were associated with impaired peripheral sensory nerve function and nerve conduction after long disease duration in childhood-onset T1D.