title: Estimation of prehepatic insulin secretion: comparison between standardized C-peptide and insulin kinetic models.
abstract: Our aim was to compare traditional C-peptide-based method and insulin-based method with standardized kinetic parameters in the estimation of prehepatic insulin secretion rate (ISR). One-hundred thirty-four subjects with varying degrees of glucose tolerance received an insulin-modified intravenous glucose tolerance test and a standard oral glucose tolerance test with measurement of plasma insulin and C-peptide. From the intravenous glucose tolerance test, we determined insulin kinetics parameters and selected standardized kinetic parameters based on mean values in a selected subgroup. We computed ISR from insulin concentration during the oral glucose tolerance test using these parameters and compared ISR with the standard C-peptide deconvolution approach. We then performed the same comparison in an independent data set (231 subjects). In the first data set, total ISRs from insulin and C-peptide were highly correlated (R(2) = 0.75, P < .0001), although on average different (103 ± 6 vs 108 ± 3 nmol, P < .001). Good correlation was also found in the second data set (R(2) = 0.54, P < .0001). The insulin method somewhat overestimated total ISR (85 ± 5 vs 67 ± 3 nmol, P = .002), in part because of differences in insulin assay. Similar results were obtained for fasting ISR. Despite the modest bias, the insulin and C-peptide methods were consistent in predicting differences between groups (eg, obese vs nonobese) and relationships with other physiological variables (eg, body mass index, insulin resistance). The insulin method estimated first-phase ISR peak similarly to the C-peptide method and better than the simple use of insulin concentration. The insulin-based ISR method compares favorably with the C-peptide approach. The method will be particularly useful in data sets lacking C-peptide to assess β-cell function through models requiring prehepatic secretion.
authors.affiliation: Metabolic Unit, Institute of Biomedical Engineering, National Research Council, Padova, Italy. tura@isib.cnr.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Tura
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kautzky-Willer
authors.forename: Amalia
authors.initials: A
authors.lastname: Gastaldelli
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
mesh_terms: D000328:Adult; D000465:Algorithms; D015992:Body Mass Index; D002096:C-Peptide; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism; D044882:Glucose Metabolism Disorders / Q000175:diagnosis / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000032:analysis* / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology; D007700:Kinetics; D008297:Male; D015233:Models, Statistical; D010186:Pancreatic Function Tests / Q000379:methods*
chemical_list: D002096:C-Peptide; D007328:Insulin