Insulin secretion and impaired glucose tolerance

Abstract

To the Editor: The recent publication in Diabetologia ofbaseline results from two large-scale longitudinal studiesprovides welcome confirmation of the association ofimpaired beta cell function and glucose intolerance outsidethe diabetic range and promises useful information whenfollow-up studies are completed regarding factors related toprogression of glucose intolerance [1, 2]. While bothstudies conclude that beta cell function is the dominantdeterminant of glucose tolerance, they differ in onesignificant detail. Mari et al. [1] conclude that variationsin their primary index of insulin secretion (glucosesensitivity) are not associated with variations in whole-body insulin sensitivity and therefore are not related to anyfeedback relationship between beta cell function and insulinsensitivity. On the contrary, DeFronzo et al. [2] concludefrom their primary index of insulin secretion (a dispositionindex [DI]), that impairments do represent a failure offeedback between insulin sensitivity and insulin secretion.We present here an argument that the two differentinterpretations reflect the same underlying reality, which isclosest to the interpretation of Mari et al., and that theapparent difference is due to a misinterpretation of thephysiological and statistical relationships between insulinsecretion, insulin sensitivity and glucose tolerance (or othermeasures of glycaemia).We have shown elsewhere [3], using published data fromsome of the authors of Mari et al. and DeFronzo et al. [4],that glycaemic responses to an OGTT conform closely to asimple HOMA-like model [5] relating insulin secretion,insulin sensitivity and glycaemia. The model can beexpressed as:lnðÞ¼b lnðÞR