Abstract
Current closed-loop insulin delivery methods stem from sophisticated models of the glucose-insulin (G/I) system, mostly based on complex studies employing glucose tracer technology. We tested the performance of a new minimal model (GLUKINSLOOP 2.0) of the G/I system to characterize the glucose and insulin dynamics during multiple mixed meal tests (MMT) of different sizes in patients with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion, CSII). The GLUKINSLOOP 2.0 identified the G/I system, provided a close fit of the G/I time-courses and showed acceptable reproducibility of the G/I system parameters in repeated studies of identical and double-sized MMTs. This model can provide a fairly good and reproducible description of the G/I system in T1D patients on CSII, and it may be applied to create a bank of “virtual” patients. Our results might be relevant at improving the architecture of upcoming closed-loop CSII systems.
Highlights
The glucose-insulin (G/I) system is a physiological closed-loop, which is able to maintain the plasma glucose levels within a narrow physiological range, as a result of a complex interaction among many components[1,2]
Owing to the potential applicability of this work in the field of type 1 diabetes (T1D), the GLUKINSLOOP 2.0 model has been used to describe the G/I system during a mixed meal test (MMT) in patients with T1D on insulin pump therapy
We successfully tested the hypothesis that, with the aid of the “external” assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp (HEC), the G/I system would be amenable to be successfully reconstructed in T1D patients, in whom modeling of the G/I system has become a key component of therapeutic innovative strategies[43,44,45]
Summary
The glucose-insulin (G/I) system is a physiological closed-loop, which is able to maintain the plasma glucose levels within a narrow physiological range, as a result of a complex interaction among many components[1,2]. In order to mitigate the burden of both experimental and modeling complexity, more parsimonious models, i.e. with a lower number of ODEs and of parameters, have been proposed and successfully employed[6,15,23,28,29,30,31,32,33] These “minimal models” have been far applied most frequently to the intravenous glucose tolerance tests (IVGTT) with the primary aim of measuring insulin sensitivity[6,14,33]. Current minimal modeling of glucose/carbohydrate meals with no tracer(s) aid, even though calibrated to successfully handle the oral glucose rate of appearance with a set of constrained parameters[31,36], provides estimates of insulin sensitivity which, albeit correlated to those obtained with reference methods, display significant deviations from all other methods for somewhat unclear reasons[26,28,31,37,38,39]. Recent real-life clinical trials have reported very promising results towards the development of a reliable, wearable closed-loop insulin delivery system[43,44,45]
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