Modeling the euglycemic hyperinsulinemic clamp by stochastic differential equations
(2006) In Journal of Mathematical Biology 53(5). p.771-796- Abstract
- The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental procedure for the determination of insulin sensitivity. In the present study, 16 subjects with BMI between 18.5 and 63.6 kg/m(2) have been studied with a long-duration (5 hours) EHC. In order to explain the oscillations of glycemia occurring in response to the hyperinsulinization and to the continuous glucose infusion at varying speeds, we first hypothesized a system of ordinary differential equations (ODEs), with limited success. We then extended the model and represented the experiment using a system of stochastic differential equations (SDEs). The latter allow for distinction between (i) random variation imputable to observation error and (ii) system noise... (More)
- The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental procedure for the determination of insulin sensitivity. In the present study, 16 subjects with BMI between 18.5 and 63.6 kg/m(2) have been studied with a long-duration (5 hours) EHC. In order to explain the oscillations of glycemia occurring in response to the hyperinsulinization and to the continuous glucose infusion at varying speeds, we first hypothesized a system of ordinary differential equations (ODEs), with limited success. We then extended the model and represented the experiment using a system of stochastic differential equations (SDEs). The latter allow for distinction between (i) random variation imputable to observation error and (ii) system noise (intrinsic variability of the metabolic system), due to a variety of influences which change over time. The stochastic model of the EHC was fitted to data and the system noise was estimated by means of a (simulated) maximum likelihood procedure, for a series of different hypothetical measurement error values. We showed that, for the whole range of reasonable measurement error values: (i) the system noise estimates are non-negligible; and (ii) these estimates are robust to changes in the likely value of the measurement error. Explicit expression of system noise is physiologically relevant in this case, since glucose uptake rate is known to be affected by a host of additive influences, usually neglected when modeling metabolism. While in some of the studied subjects system noise appeared to only marginally affect the dynamics, in others the system appeared to be driven more by the erratic oscillations in tissue glucose transport rather than by the overall glucose-insulin control system. It is possible that the quantitative relevance of the unexpressed effects (system noise) should be considered in other physiological situations, represented so far only with deterministic models. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4216014
- author
- Picchini, Umberto LU ; Ditlevsen, Susanne and De Gaetano, Andrea
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Mathematical Biology
- volume
- 53
- issue
- 5
- pages
- 771 - 796
- publisher
- Springer
- external identifiers
-
- scopus:33750539308
- ISSN
- 1432-1416
- DOI
- 10.1007/s00285-006-0032-z
- language
- English
- LU publication?
- no
- id
- 3c5993d0-1748-4e47-afbd-353b6ee63e70 (old id 4216014)
- date added to LUP
- 2016-04-01 12:00:20
- date last changed
- 2022-03-28 18:50:27
@article{3c5993d0-1748-4e47-afbd-353b6ee63e70,
abstract = {{The Euglycemic Hyperinsulinemic Clamp (EHC) is the most widely used experimental procedure for the determination of insulin sensitivity. In the present study, 16 subjects with BMI between 18.5 and 63.6 kg/m(2) have been studied with a long-duration (5 hours) EHC. In order to explain the oscillations of glycemia occurring in response to the hyperinsulinization and to the continuous glucose infusion at varying speeds, we first hypothesized a system of ordinary differential equations (ODEs), with limited success. We then extended the model and represented the experiment using a system of stochastic differential equations (SDEs). The latter allow for distinction between (i) random variation imputable to observation error and (ii) system noise (intrinsic variability of the metabolic system), due to a variety of influences which change over time. The stochastic model of the EHC was fitted to data and the system noise was estimated by means of a (simulated) maximum likelihood procedure, for a series of different hypothetical measurement error values. We showed that, for the whole range of reasonable measurement error values: (i) the system noise estimates are non-negligible; and (ii) these estimates are robust to changes in the likely value of the measurement error. Explicit expression of system noise is physiologically relevant in this case, since glucose uptake rate is known to be affected by a host of additive influences, usually neglected when modeling metabolism. While in some of the studied subjects system noise appeared to only marginally affect the dynamics, in others the system appeared to be driven more by the erratic oscillations in tissue glucose transport rather than by the overall glucose-insulin control system. It is possible that the quantitative relevance of the unexpressed effects (system noise) should be considered in other physiological situations, represented so far only with deterministic models.}},
author = {{Picchini, Umberto and Ditlevsen, Susanne and De Gaetano, Andrea}},
issn = {{1432-1416}},
language = {{eng}},
number = {{5}},
pages = {{771--796}},
publisher = {{Springer}},
series = {{Journal of Mathematical Biology}},
title = {{Modeling the euglycemic hyperinsulinemic clamp by stochastic differential equations}},
url = {{https://lup.lub.lu.se/search/files/2739939/4216015}},
doi = {{10.1007/s00285-006-0032-z}},
volume = {{53}},
year = {{2006}},
}