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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

Sample model fit obtained with subject 7. The model fit (with Model 5) to endogenous plasma insulin concentration (upper panel) with plasma glucose excursion (lower panel) during closed-loop (left panel) and control period (right panel); solid line represents model prediction, dashed line 95% intervals, the dotted vertical lines indicate meal time and full circles dots represent measurements).
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Fig4: Sample model fit obtained with subject 7. The model fit (with Model 5) to endogenous plasma insulin concentration (upper panel) with plasma glucose excursion (lower panel) during closed-loop (left panel) and control period (right panel); solid line represents model prediction, dashed line 95% intervals, the dotted vertical lines indicate meal time and full circles dots represent measurements).

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)

Sample model fit obtained with subject 7. The model fit (with Model 5) to endogenous plasma insulin concentration (upper panel) with plasma glucose excursion (lower panel) during closed-loop (left panel) and control period (right panel); solid line represents model prediction, dashed line 95% intervals, the dotted vertical lines indicate meal time and full circles dots represent measurements).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Sample model fit obtained with subject 7. The model fit (with Model 5) to endogenous plasma insulin concentration (upper panel) with plasma glucose excursion (lower panel) during closed-loop (left panel) and control period (right panel); solid line represents model prediction, dashed line 95% intervals, the dotted vertical lines indicate meal time and full circles dots represent measurements).
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