title: Hepatic insulin sensitivity in healthy and prediabetic subjects: from a dual- to a single-tracer oral minimal model.
abstract: Recently, a model was proposed to assess hepatic insulin sensitivity during a meal, i.e., the ability of insulin to suppress glucose production (EGP), SI (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 SI (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 SI (P), disposal insulin sensitivity (SI (D)), and EGP. The model fitted the data well, and SI (P) and SI (D) were estimated with precision in both databases (SI (P) = 5.48 ± 0.54 10(-4) dl·kg(-1)·min(-1) per μU/ml and SI (D) = 9.93 ± 2.18 10(-4) dl·kg(-1)·min(-1) per μU/ml in healthy; SI (P) = 5.41 ± 3.55 10(-4) dl·kg(-1)·min(-1) per μU/ml and SI (D) = 5.34 ± 6.17 10(-4) dl·kg(-1)·min(-1) per μU/ml, in healthy and prediabetic subjects). Estimated SI (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 (EGPb), and EGP/EGPb agreed with the results obtained using the triple-tracer method. In this study, we have demonstrated that SI (P), SI (D), and EGP/EGPb time course can be estimated reliably from a single-tracer meal protocol in both healthy and prediabetic subjects.
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy; and.
authors.forename: Roberto
authors.initials: R
authors.lastname: Visentin
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy; and.
authors.forename: Chiara
authors.initials: C
authors.lastname: Dalla Man
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Ananda
authors.initials: A
authors.lastname: Basu
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.affiliation: Department of Information Engineering, University of Padua, Padua, Italy; and cobelli@dei.unipd.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006262:Health; D006801:Humans; D007202:Indicators and Reagents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D008297:Male; D062407:Meals; D008875:Middle Aged; D008954:Models, Biological; D011236:Prediabetic State / Q000378:metabolism*; D011849:Radioactive Tracers
chemical_list: D007202:Indicators and Reagents; D007328:Insulin; D011849:Radioactive Tracers
keywords: glucose kinetics; insulin resistance; meal; tracer