The levels of circulating TRAIL at the onset of type 1 diabetes are markedly decreased in patients with ketoacidosis and with the highest insulin requirement.
Experimental evidence in animal models suggests that TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, might play an important role in type 1 diabetes (T1D). We have performed a retrospective study by analyzing the sera of a cohort of pediatric subjects (age ≤18 years; n = 507) consisting of (1) patients diagnosed with T1D (n = 387), (2) healthy individuals (n = 98, considered as controls), and (3) healthy autoantibody-positive subjects (n = 22). Patients with T1D exhibited significantly decreased levels of circulating TRAIL with respect to the control healthy subjects, as well as to the healthy autoantibody-positive subjects. Within the T1D group, no differences in the levels of circulating TRAIL were observed between patients with or without other concomitant autoimmune pathologies. Of note, the levels of TRAIL were significantly lower in the T1D patients analyzed at onset, although reduction in TRAIL levels persisted also in patients analyzed after disease onset (>1 year from diagnosis). In particular, T1D patients who exhibited ketoacidosis at onset showed significantly lower levels of circulating TRAIL with respect to patients without ketoacidosis at onset. Moreover, the levels of TRAIL at diagnosis correlated inversely with the insulin requirement up to 21 months of follow-up. This is the first study demonstrating that the levels of circulating TRAIL are significantly decreased in T1D, with the lowest levels of TRAIL being observed in patients with ketoacidosis at the onset and with the highest insulin requirement.
Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Via dell'Istria, 65/1, 34137, Trieste, Italy.
Gianluca
G
Tornese
Dario
D
Iafusco
Lorenzo
L
Monasta
Chiara
C
Agnoletto
Veronica
V
Tisato
Alessandro
A
Ventura
Giorgio
G
Zauli
Paola
P
Secchiero
D000293:Adolescent; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D007662:Ketosis / Q000097:blood*; D008297:Male; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*
D001323:Autoantibodies; D006442:Glycated Hemoglobin; D007328:Insulin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C517652:hemoglobin A1c protein, human