Here there find more will need to be ‘reverse translation’, because immune parameters are analysed rarely on peripheral blood and correlated with successful prevention (or lack thereof) of diabetes on an individual basis in murine studies. Surprisingly, two recent trials (Andromeda’s heat shock protein peptide

p277 and Bayhill’s proinsulin expressing DNA vaccine BHT3021; Table 4) reported positive outcomes, even in the more stringent recent-onset diabetes setting, by preserving C-peptide at certain dosing regimens. These observations exceeded expectations based on animal studies, where both strategies were only effective in preventing diabetes but not in reversing hyperglycaemia.

It will be important to explore whether, in either trial, immunological selleckchem outcomes were associated with better preservation of C-peptide and thus could perhaps pave the way in future for using such immunological end-points in staging as entry criteria, or to optimize dosing in larger trials, prior to embarking on the more arduous, expensive and time-consuming prevention trials. Recent, seminal lessons from studies on pancreatic tissue of type 1 diabetic donors provide compelling proof of the autoimmune nature of type 1 diabetes; in particular, the demonstration of β cell autoantigen-specific CD8 T cells in destructive insulitic

lesions has highlighted a link that had not emerged in 2007. Interleukin-2 receptor The persistence of β cells and insulin production as well as inflammatory insulitic lesions many years after clinical manifestations of hyperglycaemia are also arresting, providing an apparent disconnect between β cell mass and function. These studies also emphasize differences in immunopathology between men and mice; provide evidence of pathological and aetiological heterogeneity [43-49]; and provide potential new biomarkers and therapeutic targets centred on CD8 T cell biology [50-53] that were not envisaged at the time of our last review(Fig. 3). Importantly, the ‘biomarker concept’ that has become a critical piece of new drug development in the pharma industry has also begun to feature strongly in current thinking about type 1 diabetes therapies [5]; the term was not even used in the previous paper [1]. There is probably more new insight to be gained from studying the diabetic pancreas in settings such as nPOD. For example, the observation that the remaining β cell mass at clinical manifestation of disease may be substantial (as much as 50%, rather than 10–20% cited in most textbooks) disproves a common assumption that the disease process has always reached an end-stage at this point.