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Insulin Secretion Rate During Glucose Stimuli: Alternative Analyses of C-Peptide Data

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Abstract

The ability to evaluate the pancreatic insulin secretion rate (ISR) is essential for a quantitative understanding of the glucose regulation system in man. Various approaches have been developed for evaluation of the ISR in vivo. The aim of this study was to compare input/output and compartmental models of C-peptide to reconstruct the ISR in response to both physiological and nonphysiological glucose stimuli in healthy humans. In particular we applied the nonparametric stochastic deconvolution and the C-peptide minimal model approaches to the graded up&down glucose infusion protocol, where glucose was infused at progressively increasing and then decreasing rates, and to the intravenous glucose tolerance test (IVGTT), where an impulse dose of glucose was administered. Our results show that the two models give virtually identical results when glucose and C-peptide (and thus ISR) profiles are smooth and regular, but when vigorous nonstationarities are present, like during the first 4 min of the IVGTT, the two ISR profiles are different (but not their areas under the curve). The C-peptide minimal model, albeit requiring, at variance with deconvolution, the knowledge of glucose data, has the advantage of providing quantitative indices of the β-cell function, which is important in the parametric definition of different physiopathological states. © 2001 Biomedical Engineering Society.

PAC01: 8715Rn, 8714Ee, 8716Ac

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References

  1. Barret, P. H. R., B. M. Bell, C. Cobelli, H. Golde, A. Schumitzky, P. Vicini, and D. Foster. SAAM II: Simulation, analysis and modeling software for tracer and pharmacokinetic studies. Metabolism47:484–492, 1998.

    Google Scholar 

  2. Carson, E. R., C. Cobelli, and L. Finkelstein. The Mathematical Modeling of Metabolic and Endocrine Systems. New York: Wiley, 1983.

    Google Scholar 

  3. Cobelli, C., D. Foster, and G. Toffolo. Tracer Kinetic in Biomedical Research: From Data to Model. New York: Kluwer Academic, 2000.

    Google Scholar 

  4. De Nicolao, G.and D. Liberati. Linear and nonlinear techniques for the deconvolution of hormone time-series. IEEE Trans. Biomed. Eng.40:440–455, 1993.

    Google Scholar 

  5. De Nicolao, G., G. Sparacino, and C. Cobelli. Nonparametric input estimation in physiological systems: Problems, methods, case studies. Automatica33:851–870, 1997.

    Google Scholar 

  6. Eaton, R. P., R. C. Allen, D. S. Schade, K. M. Erickson, and J. Standefer. Prehepatic insulin production in man: Kinetic analysis using peripheral connecting peptide behaviour. J. Clin. Endocrinol. Metab.51:520–28, 1980.

    Google Scholar 

  7. Faber, O. K., C. Binder, J. Markussen, L. G. Heding, V. K. Naithani, H. Kuzuya, P. Blix, D. L. Horwitz, and A. H. Rubenstein. Characterization of seven C-peptide antisera. Diabetes27:170–177, 1978.

    Google Scholar 

  8. Hovorka, R., L. Chassin, S. D. Luzio, R. Playle, and D. R. Owens. Pancreatic β cell responsiveness during meal tolerance test: Model assessment in normal subjects and subjects with newly diagnosed noninsulin-dependent diabetes mellitus. J. Clin. Endocrinol. Metab.83:744–750, 1998.

    Google Scholar 

  9. Hovorka, R., P. A. Soons, and M. A. Young. ISEC: A program to calculate insulin secretion. Comput. Methods Programs Biomed.50:253–264, 1996.

    Google Scholar 

  10. Polonsky, K. S.and A. H. Rubenstein. C-peptide as a measure of the secretion and hepatic extraction of insulin: Pitfalls and limitations. Diabetes33:486–494, 1984.

    Google Scholar 

  11. Polonsky, K. S., J. Licinio-Paixao, B. D. Given, W. Pugh, P. Rue, J. Galloway, T. Karrison, and B. Frank. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J. Clin. Invest.51:98–105, 1986.

    Google Scholar 

  12. Sparacino, G.and C. Cobelli. A stochastic deconvolution method to reconstruct insulin secretion rate after a glucose stimulus. IEEE Trans. Biomed. Eng.43:512–529, 1996.

    Google Scholar 

  13. Sparacino, G., G. Pillonetto, M. Capello, G. De Nicolao, and C. Cobelli. WINSTODEC: A Stochastic Deconvolution interactive program for physiological and pharmacokinetic systems. Comput. Methods Programs Biomed. (in press).

  14. Toffolo, G., E. Breda, M. K. Cavaghan, D. A. Ehrmann, K. S. Polonsky, and C. Cobelli. Quantitative indexes of β cell function during graded up&down glucose infusion from C-peptide minimal models. Am. J. Physiol. Endocrinol. Metab.280:E2–E10, 2001.

    Google Scholar 

  15. Toffolo, G., F. De Grandi, and C. Cobelli. Estimation of β-cell sensitivity from IVGTT C-peptide data. Knowledge of the kinetics avoids errors in modeling the secretion. Diabetes44:845–854, 1995.

    Google Scholar 

  16. Van Cauter, E., F. Mestrez, J. Sturie, and K. S. Polonsky. Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes41:368–377, 1992.

    Google Scholar 

  17. Vølund, A., K. S. Polonsky, and R. N. Bergman. Calculated pattern of interportal insulin appearance without independent assessment of C-peptide kinetics. Diabetes36:1195–1202, 1987.

    Google Scholar 

  18. Watanabe, R. M., A. Vølund, S. Roy, and R. N. Bergman. Pre-hepatic beta-cell secretion during the intravenous glucose tolerance test in humans: Application of a combined model of insulin and C-peptide kinetics. J. Clin. Endocrinol. Metab.69:790–797, 1989.

    Google Scholar 

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Breda, E., Cobelli, C. Insulin Secretion Rate During Glucose Stimuli: Alternative Analyses of C-Peptide Data. Annals of Biomedical Engineering 29, 692–700 (2001). https://doi.org/10.1114/1.1385804

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