[Subclassification of seronegative type 1 diabetic subjects with HLA-DQ genotypes].

ObjectiveTo reveal the relationship between disease phenotype and HLA-DQ genotype in autoantibody-negative type 1 diabetics and to explore whether HLA-DQ genotypes can reclassify seronegative type 1 diabetic patients. MethodsSixty-one diabetics with unprovoked ketosis or ketoacidosis at presentation were tested for glutamic acid decarboxylase antibody (GAD-Ab)?tyrosine phosphata se antibody (IA2-Ab)?thyroglobulin antibody(TGA)?thyroid peroxidase antibody (TPO-Ab) and HLA-DQ genotype. GAD-Ab and IA2-Ab were measured with radioligand assay. TGA and TPO-Ab were evaluated using RIA. Sequence-based genotyping (SBT) was used to determine the alleles of HLA-DQA1 and DQB1. Autoantibody negative patients were subdivided into group A (with type 1 diabetes susceptible alleles) and group B (without type 1 diabetes susceptible alleles).Clinical characteristics, including age, sex, mode of presentation, body mass index (BMI), islet beta-cell function and current treatment were compared between the autoantibody-positive and autoantibody-negative patients and between group A and B. ResultsAmong the 61 patients, 29 (47.5%) were negative for all the antibodies tested, while 31 (50.8%) were positive for one or more antibodies tested. 5 (8.2%) were positive for all those 4 antibodies. As for genetic analysis, 18 of the 29 seronegative patients carried 1-4 HLA-DQ risk alleles, while the other 11 did not carry any type 1 diabetes susceptible alleles tested. As compared with the autoantibody-negative patients, younger age at onset, less obesity, severer degree of diabetic ketoacidosis (DKA) and lower C peptide were found in the autoantibody-positive ones . As compared with group B, less obesity [BMI:(22.4±4.4) kg/m 2 vs (25.8±3.7) kg/m 2, P=0.03], severer degree of DKA[CO 2CP: (16.3±7.1) [LM]mmol/L vs (19.2±2.0) mmol/L, P=0.01; pH: 7.26±0.20 vs 7.34±0.06, P=0.03], and lower C peptide , and lower C peptide [fasting C peptide: (254.6±189.4) pmol/L vs (458.7±274.1) pmol/L, P=0.06] were observed in group A. During follow-up, 73%(8/11) patients in group B discontinued insulin therapy and maintained acceptable glycemic control by either diet or oral hypoglycemic agents (OHA), while only 28% (5/18) of the patients in group A discontinued and maintained control with OHA (28% vs 73%, P0.01). Among those who kept on using insulin, group A patients required higher insulin dosage than those of group B [(0.43±0.16) U·kg -1 ·d -1 vs (0.24±0.18) U·kg -1 ·d -1 , P=0.07]. ConclusionsAutoantibody-negative diabetics, if with susceptible HLA-DQ genotypes, presented more type 1A-like features, implying possible existence of as yet unidentified immunologic abnormalities in these patients. HLA-DQ risk genotypes may reclassify seronegative type 1 diabetics. Those who are autoantibody negative but carry susceptible HLA-DQ genotypes, should not be diagnosed as type 1B diabetes.