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Review
. 2021 Jul 16:12:611512.
doi: 10.3389/fendo.2021.611512. eCollection 2021.

Adapting Protocols or Models for Use in Insulin-Requiring Diabetes and Islet Transplant Recipients

Glenn M Ward  1   2   3 , Jacqueline M Walters  1   3 , Judith L Gooley  1   3 , Raymond C Boston  1   3   4
Affiliations
Review

Adapting Protocols or Models for Use in Insulin-Requiring Diabetes and Islet Transplant Recipients

Glenn M Ward et al. Front Endocrinol (Lausanne). .

Abstract

The authors' perspective is described regarding modifications made in their clinic to glucose challenge protocols and mathematical models in order to estimate insulin secretion, insulin sensitivity and glucose effectiveness in patients living with Insulin-Requiring Diabetes and patients who received Pancreatic Islet Transplants to treat Type I diabetes (T1D) with Impaired Awareness of Hypoglycemia. The evolutions are described of protocols and models for use in T1D, and Insulin-Requiring Type 2 Diabetes (T2D) that were the basis for studies in the Islet Recipients. In each group, the need for modifications, and how the protocols and models were adapted is discussed. How the ongoing application of the adaptations is clarifying the Islet pathophysiology in the Islet Transplant Recipients is outlined.

Keywords: C-peptide model; insulin secretion; insulin sensitivity; islet transplantation; mathematical modeling; minimal model; type 1 diabetes mellitus.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Modifications to the Bergman minimal model of the intravenous tolerance test, aimed at enabling the model to be applied to data from T1D subjects in whom endogenous insulin secretion was minimal compared with the exogenous insulin infusion. Note that the endogenous coupling of the plasma insulin response to plasma glucose that was used in our modeling of non-diabetic subjects (5) was replaced with an external insulin supply represented by an additional compartment, as described in reference . This figure has been reproduced in a modified form from with permission.
Figure 2
Figure 2
Exogenous insulin protocol in T2D. This figure has been reproduced in a modified form from with permission. It shows the steps of insulin infusion used in the T2D protocol, but also is similar in principle to the stepped protocol used for T1D.
Figure 3
Figure 3
Modification of Minimal Model to accommodate T2D data with the physiological exogenous insulin protocol. This figure has been reproduced in a modified form from with permission. The IVGTT glucose and insulin data were analyzed using the glucose model of Bergman et al. as described (5) using the simulation, analysis, and modeling program SAAM (6). Except there were the following modifications: The square around compartment “I” indicates that the observed plasma insulin concentrations drive the system, and an additional element that is the equivalent of two linked compartments represents a time delay in the transfer of insulin into the remote insulin compartment (X). The program SAAM generates and numerically solves the differential equations without the need to supply explicit differential equations representing the time delay element.
Figure 4
Figure 4
The post-transplant first-phase insulin secretion (Phi1) during an IVGTT, when calculated by ISEC analysis of plasma C-peptide levels, was reduced in insulin independent Islet Transplant recipients - compared with matched healthy controls.
Figure 5
Figure 5
Mean ± SE plasma glucose concentrations during 75g OGTTs in the 7 Insulin-independent Islet Transplant Recipients, and in the 9 Nondiabetic Controls.
Figure 6
Figure 6
Mean ± SE Pre-hepatic insulin secretion rates estimated from the plasma C-peptide concentrations by deconvolution using the program ISEC, during 75g OGTTs in the 7 Insulin-independent Islet Transplant Recipients, and in the 9 Nondiabetic Controls.
See this image and copyright information in PMC

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