orals Australasian Diabetes in Pregnancy Annual Scientific Meeting 2013

ZINC TRANSPORTER 8 ANTIBODIES IN GESTATIONAL DIABETES AND POST-PARTUM: PREVALENCE, PHENOTYPIC ASSOCIATIONS AND NEONATAL OUTCOMES (#18)

Victoria Rudland 1 2 , Jenecia Wong 1 3 , Christine Pech 1 , Anna-Jane Harding 1 , Kris Tan 1 , Kim Lee 1 , Lynda Molyneaux 1 , Dennis K Yue 1 2 , Glynis P Ross 1
  1. Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  2. The University of Sydney, Sydney, NSW, Australia
  3. The University of Sydney, Sydney, NSW, Australia

Background: Zinc transporter 8 (ZnT8) antibodies are highly β-cell specific and tend to persist through prediabetes to diagnosis of diabetes.  The presence of ZnT8 antibodies during gestational diabetes (GDM) pregnancies is less well studied and may identify patients at risk of future autoimmune diabetes. 

Aims: To investigate the prevalence and clinical associations of ZnT8 antibodies in GDM patients, at diagnosis and post-partum. 

Methods: Patients diagnosed with GDM at Royal Prince Alfred Hospital were assessed at diagnosis and 3 months post-partum.  Sera were analysed for ZnT8 antibodies using a commercial ELISA that detects the 325Arg and 325Trp variants.  GAD, IA2 and insulin antibodies were analysed using commercial radioimmunoassays.

Results: 302 women with GDM were recruited. 163 attended post-partum testing.  ZnT8 antibody testing was performed in 271 patients antepartum and 124 patients post-partum.  The prevalence of ZnT8 antibody positivity was 4.8% antepartum and 1.6% post-partum.  The overall prevalence of any antibody positive was 9.9% antepartum and 12.3% post-partum (Table 1).  

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Of those patients with a positive antibody during pregnancy who attended post-partum testing, ZnT8 antibody titre significantly decreased from pregnancy to post-partum (Figure 1) whereas there was no significant change in titre for patients with a positive GAD, IA2 or insulin antibody (Table 2). 

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When ZnT8 antibody titres were stratified by quartiles, there were no significant differences between quartiles in maternal phenotype, degree of hyperglycaemia, insulin treatment or neonatal outcomes.

Conclusions: ZnT8 antibody was the most prevalent antibody during GDM pregnancies but was not associated with maternal demographics, glycaemic control or neonatal outcomes.  The decline in ZnT8 antibody titre from antepartum to post-partum was unexpected, given the relative immunosuppression in pregnancy.  This may represent a change in islet cell hyper-reactivity, possibly related to hormonal or placental factors. 

Further studies may identify the significance of positive ZnT8 antibodies in GDM that persist post-partum. 

  1. Wenzlau JM et al. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. PNAS 2007; 104:17040-17045.