title: Insulin sensitivity index in type 1 diabetes and following human islet transplantation: comparison of the minimal model to euglycemic clamp measures.
abstract: Insulin sensitivity is impaired in type 1 diabetes (T1D) and may be enhanced by islet transplantation, an effect best explained by improved metabolic control. While the minimal model index of insulin sensitivity, SI, has been used in studies of T1D, it has not before been evaluated against gold-standard measures derived from the euglycemic clamp. We sought to determine how well minimal model SI derived from an insulin-modified frequently sampled intravenous glucose tolerance (FSIGT) test compared with total body and peripheral insulin sensitivity estimates derived from the hyperinsulinemic-euglycemic clamp in subjects with T1D and following islet transplantation. Twenty-one T1D subjects were evaluated, including a subgroup (n = 12) studied again after intrahepatic islet transplantation, with results compared with normal controls (n = 11 for the FSIGT). The transplant recipients received 9,648 ± 666 islet equivalents/kg with reduction in HbA1c from 7.1 ± 0.2 to 5.5 ± 0.1% (P < 0.01) and 10/12 were insulin independent. FSIGT-derived SI was reduced in T1D pre- compared with posttransplant and with normal [1.76 ± 0.45 vs. 4.21 ± 0.34 vs. 4.45 ± 0.81 × 10(-4)(μU/ml)(-1)·min(-1); P < 0.01 for both]. Similarly, clamp-derived total body, and by the isotopic dilution method with [6,6-(2)H2]glucose, peripheral insulin sensitivity increased in T1D from pre- to posttransplant (P < 0.05 for both). The predictive power (r(2)) between volume-corrected SIC and measures of total and peripheral insulin sensitivity was 0.66 and 0.70, respectively (P < 0.00001 for both). That the minimal model SIC is highly correlated to the clamp-derived measures indicates that the FSIGT is an appropriate methodology for the determination of insulin sensitivity in T1D and following islet transplantation.
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; rickels@mail.med.upenn.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Rickels
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Kong
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Carissa
authors.initials: C
authors.lastname: Fuller
authors.affiliation: Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dalton-Bakes
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Jane F
authors.initials: JF
authors.lastname: Ferguson
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania;
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: Monell Chemical Senses Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; and.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Teff
authors.affiliation: Division of Transplantation, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ali
authors.initials: A
authors.lastname: Naji
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000601:surgery; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007328:Insulin
keywords: frequently sampled intravenous glucose tolerance test; glucose effectiveness