Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

Thomas Solomon, Steven K Malin, Kristian Karstoft, Sine H Knudsen, Jacob M Haus, Matthew J Laye, Maria Pedersen, Bente K Pedersen, John P Kirwan

20 Citations (Scopus)

Abstract

Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SIOGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SIOGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that β-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT.

Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume307
Issue number9
Pages (from-to)E822-9
Number of pages8
ISSN0193-1849
DOIs
Publication statusPublished - 1 Nov 2014

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