title: Numerical non-identifiability regions of the minimal model of glucose kinetics: superiority of Bayesian estimation.
abstract: The so-called minimal model (MM) of glucose kinetics is widely employed to estimate insulin sensitivity (S(I)) both in clinical and epidemiological studies. Usually, MM is numerically identified by resorting to Fisherian parameter estimation techniques, such as maximum likelihood (ML). However, unsatisfactory parameter estimates are sometimes obtained, e.g. S(I) estimates virtually zero or unrealistically high and affected by very large uncertainty, making the practical use of MM difficult. The first result of this paper concerns the mathematical demonstration that these estimation difficulties are inherent to MM structure which can expose S(I) estimation to the risk of numerical non-identifiability. The second result is based on simulation studies and shows that Bayesian parameter estimation techniques are less sensitive, in terms of both accuracy and precision, than the Fisherian ones with respect to these difficulties. In conclusion, Bayesian parameter estimation can successfully deal with difficulties of MM identification inherently due to its structure.
authors.affiliation: Dipartimento di Ingegneria dell'Informazione, Università degli Studi di Padova, Via Gradenigo 6b, 35131 Padova, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Pillonetto
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sparacino
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D001499:Bayes Theorem; D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009716:Numerical Analysis, Computer-Assisted
chemical_list: D001786:Blood Glucose