Is type 2 diabetes an amyloidosis and does it really matter (to patients)?

Abstract

Degeneration of pancreatic islet beta cells is increasingly ranked as a key disease mechanism in type 2 diabetes [1, 2], but it is not entirely clear what the underlying molecular processes might be and how they attack insulin production, ultimately causing type 2 diabetes [3, 4]. However, recent studies based on quantitative measurements in post mortem pancreatic tissue from humans with type 2 diabetes have reinforced earlier observations concerning the probable role of lowered beta cell numbers [5, 6] and pointed to a linkage between beta cell disappearance and beta cell apoptosis [7, 8]. ‘Glucotoxicity’ and ‘lipotoxicity’ are widely discussed possible causes of beta cell failure, but both are thought to exert their effects only after significant metabolic deterioration and functional islet impairment are already well underway [9] and so cannot be the prime movers. So what might the initiating insults be? Recent data from genome-wide association studies have highlighted the impact of particular alleles of certain susceptibility genes, giving further support to the idea that beta cell abnormalities are fundamental in the pathogenesis of this disease [4]. Some of these alleles encode variants of certain beta cell proteins linked to insulin production and/or secretion, and can hasten the development of functional islet deterioration and diabetes onset in carriers [1, 2]. However, currently identified alleles do not provide an explanation for most cases of ‘common or garden’ type 2 diabetes [10]. Against this background, Zraika et al. in this issue of Diabetologia have reviewed aspects of another, underappreciated phenomenon, which could well initiate beta cell degeneration in type 2 diabetes [11]. As they point out, it has long been known that many [8, 12–14] or perhaps most [15, 16] type 2 diabetic patients are found to have islet amyloid deposits adjacent to their beta cells [17] when post mortem pancreatic tissue is examined histologically. Although islet amyloid has also been reported to occur in numbers of humans not known to have diabetes, the author of a major study cautioned that ‘nondiabetic persons with hyaline islets may represent individuals with undiagnosed or potential diabetes’ [18]. Varying sensitivities of different histological methods may also have contributed to betweenstudy differences in prevalence estimates [11]. Islet amyloid, or hyaline as it was once known [12], has the beta cell hormone human amylin or human islet G. J. S. Cooper (*) : J. F. Aitken : S. Zhang School of Biological Sciences, and Maurice Wilkins Centre of Excellence for Molecular Biodiscovery, Faculty of Science, University of Auckland, Auckland, New Zealand e-mail: g.cooper@auckland.ac.nz