title: Low serum TNF-alpha levels in subjects at risk for type 1 diabetes.
abstract: OBJECTIVE
  The aim of our study was to determine whether serum TNF-alpha levels in individuals at risk of developing type 1 diabetes, such as first-degree relatives of diabetic patients and children with incidental hyperglycemia, underwent alterations, and also to establish whether these levels might be used to identify individuals prior to insulin dependence.
  
  
  METHODS
  We studied 71 healthy first-degree relatives (FDR) of type 1 diabetic patients and 11 children with incidental hyperglycemia. We looked for immunogenetic (HLA class II serologic alleles and HLA-DQ alpha/beta genomic polymorphisms), immunologic (islet-cell and insulin autoantibodies) 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 incidental hyperglycemia (median: 10.83 pg/ml) (p<0.0001) compared to controls (median: 76.56 pg/ml). No significant difference was observed between subjects with or without immunogenetic, immunologic and metabolic markers of type 1 diabetic risk. A negative correlation was found between serum TNF-alpha and HbA1c levels (r=-0.27, p=0.023). Two children with incidental hyperglycemia, whose TNF-alpha levels were very low, developed type 1 diabetes 6 and 8 months after this study.
  
  
  CONCLUSIONS
  Our results are compatible with an impaired immune system in the 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.
authors.affiliation: Department of Pediatrics, IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Vitali
authors.forename: M
authors.initials: M
authors.lastname: De Amici
authors.forename: G
authors.initials: G
authors.lastname: d'Annunzio
authors.forename: M
authors.initials: M
authors.lastname: Martinetti
authors.forename: A
authors.initials: A
authors.lastname: Alibrandi
authors.forename: R
authors.initials: R
authors.lastname: Lorini
mesh_terms: D000483:Alleles; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D005260:Female; D005802:Genes, MHC Class II; D006801:Humans; D006943:Hyperglycemia / Q000150:complications; D008297:Male; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D014409:Tumor Necrosis Factor-alpha