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GADA concentration is not related to the clinical course of LADA (#303)

Shanal Kumar 1 , E Curley 2 , C Luk 2 , S Fourlanos 1
  1. Dept Diabetes & Endocrinology, Royal Melbourne Hospital, Parkville, VIC, Australia
  2. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia

Background and Aim

Latent Autoimmune Diabetes in Adults (LADA) is associated with glutamic-acid decarboxylase (GADA) and islet-cell antigen 2 (IA2A) autoantibodies. Higher concentration GADA has been considered to potentially reflect more aggressive islet autoimmunity and affect the clinical course of patients with LADA.1  This study aimed to further investigate the relationship between GADA concentrations and the clinical features and course of LADA.

Methods

We performed a retrospective study of LADA patients (n=306) with confirmed GADA positivity. Concentration of GADA was expressed as folds above the upper limit of normal (ULN) reference range. The cohort was divided into either ‘higher’ or ‘lower’ GADA concentrations based on being above or below the median GADA for the entire cohort (ie. 10.7 fold above the reference range). Clinical features assessed included age at diabetes diagnosis, time to autoantibody detection, time to insulin therapy, body mass index (BMI) at diagnosis, IA2A presence and fasting C-peptide/glucose ratio as an index of beta-cell function.

Results

Overall for the Melbourne LADA cohort the mean age was 65.2 ± 15.9 years, 28% were IA2A positive, 71% progressed to insulin therapy and the mean follow-up time was 13.6 ± 9.8 years. There was no significant difference in the higher versus lower concentration GADA groups in age at diabetes diagnosis, BMI, fasting C-peptide/glucose ratio, proportion requiring insulin therapy and time to progression to insulin (Table 1). Overall there was no correlation between GADA concentration and time to insulin (r2=0.03). However the higher concentration GADA group had a higher frequency of IA2A seropositivity (40% vs 29%, p= 0.014) and earlier detection of autoimmunity following diagnosis of diabetes (5.6 years vs 9.7 years, p= < 0.001).

Conclusion

Age at diabetes diagnosis and progression to insulin in LADA appears to be less related to GADA concentration. Higher GADA concentration appears to be associated with earlier detection of autoimmunity and IA2A positivity.

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  1. van Deutekom AW, Heine RJ, Simsek S. The islet autoantibody titres: Their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus. Diabet Med. 2008;25(2):117-125.