Influence of Sex and Age at Onset on Autoantibodies against Insulin, GAD₆₅ and IA2 in Recent Onset Type 1 Diabetic Patients

Abstract

Methods: Autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA) and tyrosine phosphatase IA2 (IA2A) were measured in sera from 448 recent onset patients with type 1 diabetes mellitus (DM) subdivided according to sex (194 female and 254 male) and age at onset (134 patients diagnosed before 10 years, 187 between 10 and 20 years, 66 between 20 and 30 years and 61 over 30 years. Results: Autoantibodies were more frequent in female DM patients (93.8 vs. 86.6%, p = 0.013) due to an increased prevalence of both GADA (86.1 vs. 70.1%) and IA2A (59.3 vs. 49.2%), with GADA levels also significantly higher in women (0.24 vs. 0.18 U, p = 0.0003). When age groups were compared, there was a reduction in prevalence in patients over 20 years for both IAA (70% for patients diagnosed under 20 and 36% for older patients) and IA2A (65 and 25%, respectively). These differences also affected IAA levels, with the highest antibody titres in the youngest group (1,214.1 nU/ml in children under 10 compared to 546.9, 345.6 and 341.1 nU/ml in the subsequent groups; p < 10^–4). GADA prevalence did not differ significantly between age groups but, nevertheless, autoantibody levels were highest among the oldest type 1 DM patients (0.327 U compared to 0.216, 0.197 and 0.176 U in the decreasing age groups; p < 10^–4). Conclusion: There are sex- and age-related differences affecting the presence and/or titres of β cell autoantibodies. We speculate that these differences could reflect the severity and specificity of the autoimmune attack against the endocrine pancreas and might influence the rate of progression to type 1 DM or the risk of developing other autoimmune diseases.

Organ Specific Autoantibodies in Preclinical and Early Clinical Type 1 Diabetes in Turkey

“…It has been shown that GADA and IAA in recent onset T1D patients were more frequent among female (25), similarly our findings support that IAA titers were higher in females compared to males (p=0.026, r=0.26). The same study demonstrated higher GADA titers in older patients as shown in our study (p<0.001, r=0.502).…”

Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY

“…Diagnosis of the disease was done according to the World Health Organization (WHO) criteria [17]. All patients with type 1 diabetes (average onset age 8.8 ± 3.9 years) were positive for one or more of the measured pancreatic autoantibodies (IAA, GADA and IA2A) determined in serum at diagnosis, using previously described standardized radio-assays [1]. …”

“…In this disorder, glutamic acid decarboxylase (GADA), tyrosine phosphatase (IA2A), zinc transporter 8 (ZnT8A) and insulin autoantibodies (IAA) are currently recognized as autoimmune process markers [1, 2]. The pathogenesis of the disease is determined by complex interactions between several genetic loci and environmental factors.…”

Incidence of childhood-onset type 1 diabetes in Biscay, Spain, 1990-2013

“…GADA and IA2A were detected using standard radiobinding assays with [ 35 S]‐labelled recombinant human GAD 65 and IA2 antigens obtained by in vitro translation using cDNA clones kindly provided by Dr Å. Lernmark (University of Washington, Seattle, WA, USA) and Dr E. Bonifacio (Istituto Scientifico San Raffaele, University of Milan, Italy), respectively . Cruces Hospital Laboratory participated in different Immunology of Diabetes Workshop (IDW) Proficiency Tests, generally obtaining 100% sensitivity and specificity for all three antibody assays .…”