Modelling the effect of insulin on the disposal of meal-attributable glucose in type 1 diabetes.
The management of postprandial glucose excursions in type 1 diabetes has a major impact on overall glycaemic control. In this work, we propose and evaluate various mechanistic models to characterize the disposal of meal-attributable glucose. Sixteen young volunteers with type 1 diabetes were subject...
| Published in: | Medical & Biological Engineering & Computing Vol. 55; no. 2; pp. 271 - 283 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Published: |
Springer Nature
Feb2017
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=121002490&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 121002490 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 01400118 PO0 jtl: Medical & Biological Engineering & Computing issn: 01400118 maglogo: N pubinfo: dt: Feb2017 vid: 55 iid: 2 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 121002490 121002490 NLM27155940 10.1007/s11517-016-1509-6 NLM27155940 121002490 ppf: 271 ppct: 12 formats: fmt: @attributes: type: P tig: atl: Modelling the effect of insulin on the disposal of meal-attributable glucose in type 1 diabetes. aug: au: García-García, Fernando Hovorka, Roman Wilinska, Malgorzata Elleri, Daniela Hernando, M. García-García, Fernando Wilinska, Malgorzata E Hernando, M Elena affil: Wellcome Trust-MRC Institute of Metabolic Science , University of Cambridge , Cambridge UK sug: subj: Diabetes Mellitus, Type 1 Metabolism Models, Biological Insulin Therapeutic Use Glucose Metabolism Postprandial Period Physiology Female Young Adult Blood Glucose Metabolism Insulin Blood Models, Theoretical Diabetes Mellitus, Type 1 Drug Therapy Adolescence Reproducibility of Results Male Impact of Events Scale Scales Adolescent: 13-18 years Female Male ab: The management of postprandial glucose excursions in type 1 diabetes has a major impact on overall glycaemic control. In this work, we propose and evaluate various mechanistic models to characterize the disposal of meal-attributable glucose. Sixteen young volunteers with type 1 diabetes were subject to a variable-target clamp which replicated glucose profiles observed after a high-glycaemic-load ([Formula: see text]) or a low-glycaemic-load ([Formula: see text]) evening meal. [6,6-[Formula: see text]] and [U-[Formula: see text];1,2,3,4,5,6,6-[Formula: see text]] glucose tracers were infused to, respectively, mimic: (a) the expected post-meal suppression of endogenous glucose production and (b) the appearance of glucose due to a standard meal. Six compartmental models (all a priori identifiable) were proposed to investigate the remote effect of circulating plasma insulin on the disposal of those glucose tracers from the non-accessible compartments, representing e.g. interstitium. An iterative population-based parameter fitting was employed. Models were evaluated attending to physiological plausibility, posterior identifiability of their parameter estimates, accuracy-via weighted fitting residuals-and information criteria (i.e. parsimony). The most plausible model, best representing our experimental data, comprised: (1) a remote effect x of insulin active above a threshold [Formula: see text] = 1.74 (0.81-2.50) [Formula: see text] min[Formula: see text] [median (inter-quartile range)], with parameter [Formula: see text] having a satisfactory support: coefficient of variation CV = 42.33 (31.34-65.34) %, and (2) steady-state conditions at the onset of the experiment ([Formula: see text]) for the compartment representing the remote effect, but not for the masses of the tracer that mimicked endogenous glucose production. Consequently, our mechanistic model suggests non-homogeneous changes in the disposal rates for meal-attributable glucose in relation to plasma insulin. The model can be applied to the in silico simulation of meals for the optimization of postprandial insulin infusion regimes in type 1 diabetes. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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