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

• Published in: American journal of physiology: endocrinology and metabolism 2014-11, Vol.307 (9), p.E822-E829
• Main Authors: Solomon, Thomas P J, Malin, Steven K, Karstoft, Kristian, Knudsen, Sine H, Haus, Jacob M, Laye, Matthew J, Pedersen, Maria, Pedersen, Bente K, Kirwan, John P
• Format: Article
• Language: English
• Subjects: Allostasis; Blood Glucose - analysis; Cohort Studies; Denmark; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - diagnosis; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diagnosis, Differential; Disease Progression; Female; Glucose Clamp Technique; Glucose Intolerance - blood; Glucose Intolerance - diagnosis; Glucose Intolerance - metabolism; Glucose Intolerance - physiopathology; Glucose Tolerance Test; Glycated Hemoglobin A - analysis; Humans; Insulin - blood; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells - metabolism; Male; Middle Aged; Ohio; Prediabetic State - blood; Prediabetic State - diagnosis; Prediabetic State - metabolism; Prediabetic State - physiopathology
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00269.2014

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 (DI(OGTT)) 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 (S(I OGTT)) 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 S(I 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 (GSIS(OGTT)), and DI(OGTT) was calculated as the product of S(I OGTT) and GSIS(OGTT). Our novel S(I 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. GSIS(OGTT) demonstrated a significant inverse relationship with S(I OGTT). GSIS(OGTT) was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DI(OGTT) 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.