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Modelling endogenous insulin concentration in type 2 diabetes during closed-loop insulin delivery.

Ruan Y, Thabit H, Wilinska ME, Hovorka R - Biomed Eng Online (2015)

Bottom Line: The selected model successfully described endogenous insulin concentration over 24 h in both study periods and provided plausible parameter estimates.Model-derived results were in concordance with a clinical finding which revealed increased posthepatic endogenous insulin concentration during the control study period (P < 0.05).The modelling results indicated that the excess amount of insulin can be attributed to the glucose-independent effect as the glucose-dependent effect was similar between visits (P > 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK. yr233@cam.ac.uk.

ABSTRACT

Background: Closed-loop insulin delivery is an emerging treatment for type 1 diabetes (T1D) evaluated clinically and using computer simulations during pre-clinical testing. Efforts to make closed-loop systems available to people with type 2 diabetes (T2D) calls for the development of a new type of simulators to accommodate differences between T1D and T2D. Presented here is the development of a model of posthepatic endogenous insulin concentration, a component omitted in T1D simulators but key for simulating T2D physiology.

Methods: We evaluated six competing models to describe the time course of endogenous insulin concentration as a function of the plasma glucose concentration and time. The models were fitted to data collected in insulin-naive subjects with T2D who underwent two 24-h visits and were treated, in a random order, by either closed-loop insulin delivery or glucose-lowering oral agents. The model parameters were estimated using a Bayesian approach, as implemented in the WinBUGS software. Model selection criteria were used to identify the best model describing our clinical data.

Results: The selected model successfully described endogenous insulin concentration over 24 h in both study periods and provided plausible parameter estimates. Model-derived results were in concordance with a clinical finding which revealed increased posthepatic endogenous insulin concentration during the control study period (P < 0.05). The modelling results indicated that the excess amount of insulin can be attributed to the glucose-independent effect as the glucose-dependent effect was similar between visits (P > 0.05).

Conclusions: A model to describe endogenous insulin concentration in T2D including components of posthepatic glucose-dependent and glucose-independent insulin secretion was identified and validated. The model is suitable to be incorporated in a simulation environment for evaluating closed-loop insulin delivery in T2D.

No MeSH data available.


Related in: MedlinePlus

Weighted residuals during (top panel A) closed-loop and (bottom panel B) control period using Model 5.
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Fig3: Weighted residuals during (top panel A) closed-loop and (bottom panel B) control period using Model 5.

Mentions: Figure 3 shows weighted residual profiles for both closed-loop and control periods documenting overall plausible model fit to data using Model 5. Individual model fits are provided in Additional file 1. An example fit shown in Figure 4 confirms satisfactory model behaviour during both study periods and a positive correlation between plasma glucose and endogenous plasma insulin levels.Figure 3


Modelling endogenous insulin concentration in type 2 diabetes during closed-loop insulin delivery.

Ruan Y, Thabit H, Wilinska ME, Hovorka R - Biomed Eng Online (2015)

Weighted residuals during (top panel A) closed-loop and (bottom panel B) control period using Model 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359432&req=5

Fig3: Weighted residuals during (top panel A) closed-loop and (bottom panel B) control period using Model 5.
Mentions: Figure 3 shows weighted residual profiles for both closed-loop and control periods documenting overall plausible model fit to data using Model 5. Individual model fits are provided in Additional file 1. An example fit shown in Figure 4 confirms satisfactory model behaviour during both study periods and a positive correlation between plasma glucose and endogenous plasma insulin levels.Figure 3

Bottom Line: The selected model successfully described endogenous insulin concentration over 24 h in both study periods and provided plausible parameter estimates.Model-derived results were in concordance with a clinical finding which revealed increased posthepatic endogenous insulin concentration during the control study period (P < 0.05).The modelling results indicated that the excess amount of insulin can be attributed to the glucose-independent effect as the glucose-dependent effect was similar between visits (P > 0.05).

View Article: PubMed Central - PubMed

Affiliation: Department of Paediatrics, University of Cambridge, Cambridge, UK. yr233@cam.ac.uk.

ABSTRACT

Background: Closed-loop insulin delivery is an emerging treatment for type 1 diabetes (T1D) evaluated clinically and using computer simulations during pre-clinical testing. Efforts to make closed-loop systems available to people with type 2 diabetes (T2D) calls for the development of a new type of simulators to accommodate differences between T1D and T2D. Presented here is the development of a model of posthepatic endogenous insulin concentration, a component omitted in T1D simulators but key for simulating T2D physiology.

Methods: We evaluated six competing models to describe the time course of endogenous insulin concentration as a function of the plasma glucose concentration and time. The models were fitted to data collected in insulin-naive subjects with T2D who underwent two 24-h visits and were treated, in a random order, by either closed-loop insulin delivery or glucose-lowering oral agents. The model parameters were estimated using a Bayesian approach, as implemented in the WinBUGS software. Model selection criteria were used to identify the best model describing our clinical data.

Results: The selected model successfully described endogenous insulin concentration over 24 h in both study periods and provided plausible parameter estimates. Model-derived results were in concordance with a clinical finding which revealed increased posthepatic endogenous insulin concentration during the control study period (P < 0.05). The modelling results indicated that the excess amount of insulin can be attributed to the glucose-independent effect as the glucose-dependent effect was similar between visits (P > 0.05).

Conclusions: A model to describe endogenous insulin concentration in T2D including components of posthepatic glucose-dependent and glucose-independent insulin secretion was identified and validated. The model is suitable to be incorporated in a simulation environment for evaluating closed-loop insulin delivery in T2D.

No MeSH data available.


Related in: MedlinePlus