Minimal model S I=0 problem in NIDDM subjects: Nonzero Bayesian estimates with credible confidence intervals

Gianluigi Pillonetto, Giovanni Sparacino, Paolo Magni, Riccardo Bellazzi, Claudio Cobelli

Research output: Contribution to journalArticle


The minimal model of glucose kinetics, in conjunction with an insulin-modified intravenous glucose tolerance test, is widely used to estimate insulin sensitivity (S I). Parameter estimation usually resorts to nonlinear least squares (NLS), which provides a point estimate, and its precision is expressed as a standard deviation. Applied to type 2 diabetic subjects, NLS implemented in MINMOD software often predicts S I= 0 (the so-called "zero" S I problem), whereas general purpose modeling software systems, e.g., SAAM II, provide a very small S I but with a very large uncertainty, which produces unrealistic negative values in the confidence interval. To overcome these difficulties, in this article we resort to Bayesian parameter estimation implemented by a Markov chain Monte Carlo (MCMC) method. This approach provides in each individual the S I a posteriori probability density function, from which a point estimate and its confidence interval can be determined. Although NLS results are not acceptable in four out of the ten studied subjects, Bayes estimation implemented by MCMC is always able to determine a nonzero point estimate of S I together with a credible confidence interval. This Bayesian approach should prove useful in reanalyzing large databases of epidemiological studies.

Original languageEnglish
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number3 45-3
Publication statusPublished - 2002


  • Insulin resistance
  • Insulin sensitivity
  • Mathematical model
  • Parameter estimation
  • Type 2 diabetes

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

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