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dc.contributor.authorO'Gorman, D.
dc.contributor.authorYousif, O.
dc.contributor.authorDixon, G.
dc.contributor.authorMcQuaid, S.
dc.contributor.authorMurphy, E.
dc.contributor.authorRahman, Y.
dc.contributor.authorGasparro, D.
dc.contributor.authorPacini, G.
dc.contributor.authorNewsholme, Philip
dc.contributor.authorNolan, J.
dc.identifier.citationO'Gorman, D. and Yousif, O. and Dixon, G. and McQuaid, S. and Murphy, E. and Rahman, Y. and Gasparro, D. et al. 2008. In vivo and in vitro studies of GAD-antibody positive subjects with Type 2 diabetes: A distinct sub-phenotype. Diabetes Research and Clinical Practice. 80 (3): pp. 365-370.

The purpose of this study was to determine if immune mechanisms in GAD positive patients' contribute to the pathogenesis of a specific sub-type of Type 2 diabetes. GAD positive (n = 8) and GAD negative (n = 8) subjects diagnosed with Type 2 diabetes were matched for age, gender, body mass index, duration of diabetes and glycaemic control. All subjects underwent an insulin-modified frequently sampled intravenous glucose tolerance test to measure insulin sensitivity and insulin secretory function with minimal model analysis. In addition, BRIN-BD11 clonal ß-cells were supplemented with patients' sera to determine basal and alanine-stimulated insulin secretion and terminal complement complex (TCC) formation. Both groups were severely insulin resistant (0.56 ± 0.17 vs. 0.99 ± 0.33 10-4 min-1/(µU ml-1) for GADneg and GADpos, respectively) but the GAD negative subjects had a higher basal (87 ± 11 vs. 58 ± 14 pmol l-1, p < 0.05) and glucose-stimulated insulin secretion (?AUCins 0.96 ± 0.12 vs. 0.60 ± 0.12 pmol/(l-1 min), p < 0.05). In vivo measures of insulin secretion were negatively correlated with TCC formation, independent of antibody status. In conclusion, GAD positive subjects initially diagnosed with Type 2 diabetes are unable to compensate for insulin resistance due to more pronounced ß-cell impairment. TCC formation may be partly responsible for the insulin secretory dysfunction associated with this specific sub-type of Type 2 diabetes. © 2007 Elsevier Ireland Ltd. All rights reserved.

dc.publisherElsevier Ireland Ltd
dc.titleIn vivo and in vitro studies of GAD-antibody positive subjects with Type 2 diabetes: A distinct sub-phenotype
dc.typeJournal Article
dcterms.source.titleDiabetes Research and Clinical Practice
curtin.departmentSchool of Biomedical Sciences
curtin.accessStatusFulltext not available

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