Hepatic insulin sensitivity in healthy and prediabetic subjects: from a dual- to a single-tracer oral minimal model

• Published in: American journal of physiology: endocrinology and metabolism Vol. 309; no. 2; pp. E161 - E167
• Main Authors: Visentin, Roberto, Dalla Man, Chiara, Basu, Rita, Basu, Ananda, Rizza, Robert A., Cobelli, Claudio
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 15.07.2015
• Subjects: Administration, Oral; Adult; Diabetes; Female; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Health; Humans; Indicators and Reagents - administration & dosage; Indicators and Reagents - pharmacokinetics; Insulin; Insulin - metabolism; Insulin Resistance; Liver - metabolism; Male; Mathematical models; Meals; Middle Aged; Models, Biological; Physiology; Prediabetic State - metabolism; Radioactive Tracers; meal; tracer; insulin resistance; glucose kinetics
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00358.2014

Recently, a model was proposed to assess hepatic insulin sensitivity during a meal, i.e., the ability of insulin to suppress glucose production (EGP), S I P . The model was developed on EGP data obtained from a triple-tracer meal and the tracer-to-tracee clamp technique and validated against the euglycemic hyperinsulinemic clamp. The aim of this study was to assess whether S I P can be obtained from plasma concentrations measured after a single-tracer meal by incorporating the above EGP model into the oral glucose minimal model by describing both glucose production and disposal (OMM PD ). Triple-tracer meal data of two databases (20 healthy and 60 healthy and prediabetic subjects) were used. Virtually model-independent EGP estimates were calculated. OMM PD was identified on exogenous and endogenous glucose concentrations, providing indices of S I P , disposal insulin sensitivity (S I D ), and EGP. The model fitted the data well, and S I P and S I D were estimated with precision in both databases (S I P = 5.48 ± 0.54 10 −4 dl·kg −1 ·min −1 per μU/ml and S I D = 9.93 ± 2.18 10 −4 dl·kg −1 ·min −1 per μU/ml in healthy; S I P = 5.41 ± 3.55 10 −4 dl·kg −1 ·min −1 per μU/ml and S I D = 5.34 ± 6.17 10 −4 dl·kg −1 ·min −1 per μU/ml, in healthy and prediabetic subjects). Estimated S I P and that derived from the triple-tracer EGP model were very similar on average. Moreover, the time course of EGP normalized to basal EGP (EGP b ), and EGP/EGP b agreed with the results obtained using the triple-tracer method. In this study, we have demonstrated that S I P , S I D , and EGP/EGP b time course can be estimated reliably from a single-tracer meal protocol in both healthy and prediabetic subjects.