Low serum TNF-alpha levels in subjects at risk for type 1 diabetes

Objective: The aim of our study was to determine whether serum TNP-alpha le vels in individuals at risk of developing type 1 diabetes, such as first-de gree relatives of diabetic patients and children with incidental hyperglyce mia, underwent alterations, and also to establish whether these levels migh t be used to identify individuals prior to insulin dependence. Research design and method: We studied 71 healthy first-degree relatives (F DR) of type 1 diabetic patients and II children with incidental hyperglycem ia, We looked for immunogenetic (HLA class II serologic alleles and HLA-DQ alpha/beta genomic polymorphisms), immunologic (islet-cell and insulin auto antibodies) and metabolic (FPIR to IVGTT) markers of type 1 diabetic risk. Serum concentrations of TNF-alpha were quantified using IRMA. Results: We found significantly lower serum TNF-alpha levels in FDR of type 1 diabetic patients (median: 54.3 pg/ml) (p=0.01) and in children with inc idental hyperglycemia (median: 10.83 pg/ml) (p<0.0001) compared to controls (median: 76.56 pg/ml), No significant difference was observed between subj ects with or without immunogenetic, immunologic and metabolic markers of ty pe 1 diabetic risk. A negative correlation was found between serum TNF-alph a and HbA(1c) levels (r=-0.27, p=0.023). Two children with incidental hyper glycemia, whose TNF-alpha levels were very low, developed type I diabetes 6 and 8 months after this study. Conclusion: Our results are compatible with an impaired immune system in th e prediabetic period and suggest that serum TNF-alpha concentrations may be considered as an immunological marker useful to identify subjects at risk of developing type 1 diabetes.