GAD antibodies in T1D and LADA--relations to age, BMI, c-peptide, IA-2 and HLA-DRB1*03 and DRB1*04 alleles

Adv Gerontol. 2011;24(2):312-8.

Abstract

The determination of GADA may be useful for clinical classification of diabetes mellitus (DM) in clinically unclear cases. This GADA positivity may persist in any diabetics Type 1 Diabetes Mellitus (T1D) with an onset in adulthood and Late Autoimmune Diabetes of Adults (LADA) many years after appearance of DM. The study was aimed at comparing the levels of GADA between both diabetic subsets with their clinical parameters, age of onset DM, period of insulin need, body mass index, HbA1C, fasting and postprandial C-peptide, risky HLA-DRB1* alleles, occurrence of micro- and macrovascular diabetic complications. Further analysis of GADA titers in different time consequences to the development of DM and relations to IA-2 were made. In the study, we included 130 diabetics with an onset of diabetes (T1D or LADA) 35+ y. who were hospitalized and afterwards long-term observed in the diabetological outpatient department. Out of this number there were 62 men and 68 women of the average age 65.5 +/- 14.0 y. (range 35-93 y.). 54 were assessed as the T1D patients and 76 as the LADA ones. Patients of the T1D subgroup were GADA positive 22 times and of the LADA subgroup 21 times. LADA 2 patients that were GADA negative were more obese than GADA positive LADA diabetics (p < 0.01). Also postprandial C-peptide was higher in LADA patients GADA negative (p < 0.05). Other clinical characteristics were without statistically significant differences. We found in our diabetic patients a relation between alleles HLA-DRB1*03 and particularly combination with HLA-DRB1*04 with positive GADA levels. In the GADA negative group obesity, coronary heart disease, hypertension, syndrome of diabetic foot and dyslipidaemia appeared more frequently (OR = 2.8; 3.1; 6.2 and 2.4). We found no significant differences in observed parameters--comparison GADA positivity and negativity according to the duration of DM. GADA positive were even 10 y. duration 16 times and after 20 y. even 6 times. Recent DM had positive GADA in 11 cases and 13 cases of recent DM had GADA negative. IA-2 antibodies were positive (> 1.0 U/ml) 18 times altogether and always with positive GADA, but only 7 times in recent DM. The presence of elevated GADA identifies patients unequivocally suitable for early insulin therapy. Our observations and experiences confirm that GADA can be found increased after more than 10-20 years duration of DM, although in decreasing trend.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Autoantibodies / blood*
  • Body Mass Index
  • C-Peptide / blood
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Glutamate Decarboxylase / immunology*
  • HLA-DR Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • Male
  • Middle Aged
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / immunology

Substances

  • Autoantibodies
  • C-Peptide
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*04 antigen
  • ICA512 autoantibody
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1