Glucose allostasis: Disrobing common wisdom

Excerpt

In their article [1], Wilkin and Metcalf challenge the concept that chronic insulin resistance must be accompanied by an increase in glycaemia even in the presence of normal beta cell function [2]. In close analogy to stress models suggested by Sterling and Eyer [3] and, later, McEwen [4], we named this concept ‘glucose allostasis’. In our original paper [2], the term allostasis, which means ‘stability through change’, was used for two major reasons. First, based on an understanding of the feedback loop between plasma glucose concentrations and insulin secretion, it was considered impossible for the plasma glucose concentration to return to pre-insulin resistance concentrations, since this would remove the major stimulus for the increased insulin secretion that prevents marked increases in glycaemia with worsening insulin action. Second, this conceptual framework was evidenced by data. In Pima Indians with normal glucose tolerance, changes in insulin sensitivity were accompanied by changes in glycaemia. In the proposed model, we defined allostatic load as the detrimental effects of this elevation of plasma glucose concentration. …