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Review
. 2017 Jun;8(3):489-506.
doi: 10.1007/s13300-017-0263-6. Epub 2017 May 13.

A Review of the Current Challenges Associated with the Development of an Artificial Pancreas by a Double Subcutaneous Approach

Sverre Christian Christiansen  1   2 , Anders Lyngvi Fougner  3   4 , Øyvind Stavdahl  3 , Konstanze Kölle  3   4 , Reinold Ellingsen  5 , Sven Magnus Carlsen  6   7
Affiliations
Review

A Review of the Current Challenges Associated with the Development of an Artificial Pancreas by a Double Subcutaneous Approach

Sverre Christian Christiansen et al. Diabetes Ther. 2017 Jun.

Abstract

Introduction: Patients with diabetes type 1 (DM1) struggle daily to achieve good glucose control. The last decade has seen a rush of research groups working towards an artificial pancreas (AP) through the application of a double subcutaneous approach, i.e., subcutaneous (SC) continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion. Few have focused on the fundamental limitations of this approach, especially regarding outcome measures beyond time in range.

Methods: Based on insulin physiology, the limitations of CGM, SC insulin absorption, meal challenge, and physical activity in DM1 patients, we discuss the limitations of the double SC approach. Finally, we discuss safety measures and the achievements reported in some recent AP studies that have utilized the double SC approach.

Results: Most studies show that a double SC AP increases the time in range compared to a sensor-augmented insulin pump and shortens the time in hypoglycemia. Despite these achievements, the proportion of time spent in hyperglycemia is still roughly 20-40%, and hypoglycemia is still present 1-4% of the time. The main factors limiting further progress are the latency of SC CGM (at least 5-10 min) and the slow pharmacokinetics of SC-delivered fast-acting insulin. The maximum blood insulin level is reached after 45 min and the maximum glucose-lowering effect is observed after 1.5-2 h, while the glucose-lowering effect lasts for at least 5 h.

Conclusions: Although using a double SC AP leads to significant improvements in glucose control, the SC approach has severe limitations that hamper further progress towards a robust AP.

Keywords: Artificial pancreas; Continuous glucose monitoring; Continuous subcutaneous insulin infusion; Type 1 diabetes.

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Figures

Fig. 1a–d
Fig. 1a–d
Illustration of the concepts of a time delay (τ) and a time constant (T). The system stimulus is shown in a, while the other figures illustrate the output from a system that presents b a time delay, c a time constant, and d both. This figure is licensed for publication under a Creative Commons BY-NC-SA 4.0 license
Fig. 2
Fig. 2
Illustration of an artificial pancreas based on the double subcutaneous approach, including sources of delay. Reproduced with permission from [101]
See this image and copyright information in PMC

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