Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes

J Diabetes Investig. 2024 Jul;15(7):835-842. doi: 10.1111/jdi.14178. Epub 2024 Mar 7.

Abstract

Aims/introduction: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state.

Materials and methods: We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques.

Results: Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m2, F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively.

Conclusions: Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.

Keywords: Glutamic acid decarboxylase; Prediction; Slowly‐progressive type 1 diabetes.

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies* / blood
  • C-Peptide / blood
  • Diabetes Mellitus, Type 1* / blood
  • Diabetes Mellitus, Type 1* / diagnosis
  • Diabetes Mellitus, Type 1* / immunology
  • Disease Progression*
  • Enzyme-Linked Immunosorbent Assay*
  • Female
  • Glutamate Decarboxylase* / immunology
  • Humans
  • Insulin
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Risk Factors
  • Young Adult

Substances

  • Autoantibodies
  • Glutamate Decarboxylase
  • Insulin
  • C-Peptide