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Metabolism. 2014 Oct;63(10):1217-27. doi: 10.1016/j.metabol.2014.05.012. Epub 2014 Jun 11.

β-Cell function in type 2 diabetes.

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Department of Clinical & Experimental Medicine, University of Pisa, Italy. Electronic address:
C N R Institute of Biomedical Engineering, Padova, Italy.


Different in vivo tests explore different aspects of β-cell function. Because intercorrelation of insulin secretion indices is modest, no single in vivo test allows β-cell function to be assessed with accuracy and specificity comparable to insulin sensitivity. Physiologically-based mathematical modeling is necessary to interpret insulin secretory responses in terms of relevant parameters of β-cell function. Models can be used to analyze intravenous glucose tests, but secretory responses to intravenous glucose may be paradoxical in subjects with diabetes. Use of oral glucose (or mixed meal) data may be preferable not only for simplicity but also for physiological interpretation. While the disposition index focuses on the relationship between insulin secretion and insulin resistance, secretion parameters reflecting the dynamic response to changing glucose levels over a time frame of minutes or hours--such as β-cell glucose sensitivity--are key to explain changes in glucose tolerance and are largely independent of insulin sensitivity. Pathognomonic of the β-cell defect of type 2 diabetes is a reduced glucose sensitivity, which is accompanied by normal or raised absolute insulin secretion rates--compensatory to the attendant insulin resistance--and impaired incretin-induced potentiation. As β-cell mass is frequently within the range of nondiabetic individuals, these defects are predominantly functional and potentially reversible. Any intervention, on lifestyle or with drugs, that improves glucose tolerance does so primarily through increased β-cell glucose sensitivity. So far, however, no intervention has proven unequivocally capable of modifying the natural course of β-cell dysfunction.


Clinical testing; Insulin secretion; Type 2 diabetes; β-cell function

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