Beta cell function (revision 4)

Beta cell function is the capacity of the pancreatic beta cell to secrete insulin in amounts appropriate to the prevailing glucose concentration and to the prevailing insulin sensitivity. It is not a single quantity and cannot be measured directly in a living person; every clinical measure is an inference from insulin or C-peptide concentrations under some defined stimulus.^[1]

The central methodological difficulty is that secretion and sensitivity are not independent. A healthy beta cell compensates for insulin resistance by secreting more, so an absolute secretion figure that looks normal may represent substantial dysfunction in a very insulin-resistant person. Measures that do not adjust for sensitivity — including fasting insulin and HOMA-B — are therefore weak, and the disposition index, the product of a secretion measure and a sensitivity measure, was devised to address exactly this.^[2]

Insulin secretion cannot be sampled at source. Peripheral venous insulin has already passed the liver, which extracts a variable 40–80% at first pass, so peripheral concentration understates secretion by an amount that itself varies between people and with pulsatility.^[1]

C-peptide avoids this. It is co-secreted with insulin in equimolar amounts, is not extracted by the liver, and has predictable kinetics, so a peripheral C-peptide profile can be deconvolved into a secretion rate. This is the basis of every rigorous measure of beta-cell function.