Diabetes, Vol 49, Issue 4 580-588, Copyright © 2000 by American Diabetes Association

ARTICLES

Validation of methods for measurement of insulin secretion in humans in vivo

LL Kjems, E Christiansen, A Volund, RN Bergman and S Madsbad
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark.

To detect and understand the changes in beta-cell function in the pathogenesis of type 2 diabetes, an accurate and precise estimation of prehepatic insulin secretion rate (ISR) is essential. There are two common methods to assess ISR, the deconvolution method (by Eaton and Polonsky)-considered the "gold standard"-and the combined model (by Volund et al.). The deconvolution method is a 2-day method, which generally requires separate assessment of C-peptide kinetics, whereas the combined model is a single-day method that uses insulin and C-peptide data from a single test of interest. The validity of these mathematical techniques for quantification of insulin secretion have been tested in dogs, but not in humans. In the present studies, we examined the validity of both methods to recover the known infusion rates of insulin and C-peptide mimicking ISR during an oral glucose tolerance test. ISR from both the combined model and the deconvolution method were accurate, i.e., recovery of true ISR was not significantly different from 100%. Furthermore, both maximal and total ISRs from the combined model were strongly correlated to those obtained by the deconvolution method (r = 0.89 and r = 0.82, respectively). These results indicate that both approaches provide accurate assessment of prehepatic ISRs in type 2 diabetic patients and control subjects. A simplified version of the deconvolution method based on standard kinetic parameters for C-peptide (Van Cauter et al.) was compared with the 2-day deconvolution method, and a close agreement was found for the results of an oral glucose tolerance test. We also studied whether C-peptide kinetics are influenced by somatostatin infusion. The decay curves after bolus injection of exogenous biosynthetic human C-peptide, the kinetic parameters, and the metabolic clearance rate were similar whether measured during constant peripheral somatostatin infusion or without somatostatin infusion. Assessment of C-peptide kinetics can be performed without infusion of somatostatin, because the endogenous insulin concentration remains constant. Assessment of C-peptide kinetics with and without infusion of somatostatin results in nearly identical secretion rates for insulin during an oral glucose tolerance test.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. K. Knop, T. Vilsboll, P. V. Hojberg, S. Larsen, S. Madsbad, A. Volund, J. J. Holst, and T. Krarup Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes, August 1, 2007; 56(8): 1951 - 1959. [Abstract] [Full Text] [PDF]

				F. K. Knop, T. Vilsboll, S. Larsen, P. V. Hojberg, A. Volund, S. Madsbad, J. J. Holst, and T. Krarup Increased postprandial responses of GLP-1 and GIP in patients with chronic pancreatitis and steatorrhea following pancreatic enzyme substitution Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E324 - E330. [Abstract] [Full Text] [PDF]

				A. Caumo and L. Luzi First-phase insulin secretion: does it exist in real life? Considerations on shape and function Am J Physiol Endocrinol Metab, September 1, 2004; 287(3): E371 - E385. [Abstract] [Full Text] [PDF]

				A. D. Cherrington, D. W. Neal, D. S. Edgerton, D. Glass, L. Bowen, C. H. Hobbs, C. Leach, R. Rosskamp, and T. R. Strack Inhalation of Insulin in Dogs: Assessment of Insulin Levels and Comparison to Subcutaneous Injection Diabetes, April 1, 2004; 53(4): 877 - 881. [Abstract] [Full Text] [PDF]

				X. Chen and T. O. Scholl Ethnic Differences in C-Peptide/Insulin/Glucose Dynamics in Young Pregnant Women J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4642 - 4646. [Abstract] [Full Text] [PDF]

				M. O. Sowell, N. Mukhopadhyay, P. Cavazzoni, S. Shankar, H. O. Steinberg, A. Breier, C. M. Beasley Jr, and J. Dananberg Hyperglycemic Clamp Assessment of Insulin Secretory Responses in Normal Subjects Treated with Olanzapine, Risperidone, or Placebo J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2918 - 2923. [Abstract] [Full Text] [PDF]

				A. M. Rosenfalck, S. Maghsoudi, S. Fisker, J. O. L. Jørgensen, J. S. Christiansen, J. Hilsted, A. Vølund, and S. Madsbad The Effect of 30 Months of Low-Dose Replacement Therapy with Recombinant Human Growth Hormone (rhGH) on Insulin and C-Peptide Kinetics, Insulin Secretion, Insulin Sensitivity, Glucose Effectiveness, and Body Composition in GH-Deficient Adults J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4173 - 4181. [Abstract] [Full Text]