In vivo and in vitro studies of GAD-antibody positive subjects with Type 2 diabetes: A distinct sub-phenotype
|dc.identifier.citation||O'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.publisher||Elsevier Ireland Ltd|
|dc.title||In vivo and in vitro studies of GAD-antibody positive subjects with Type 2 diabetes: A distinct sub-phenotype|
|dcterms.source.title||Diabetes Research and Clinical Practice|
|curtin.department||School of Biomedical Sciences|
|curtin.accessStatus||Fulltext not available|
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