ABSTRACT:
Palmer2014 - Effect of IL-1β-Blocking therapies in T2DM - Disease Condition
This is the model with disease state initial conditions. A few changes were made to the model equations in order to bypass the circular dependencies apparent in SBML. Coupled algebraic equations for the species Glucose, Insulin and Proinsulin were changed to reactions which represent the ordinary differential equations found in a previously published model by De Gaetano
et al (2008), [MODEL1112110003]. This reference was used by the present authors for the algebraic equations. The original Mathematica code, obtained from the supplementary material of the article can be downloaded from the link below:
[Palmer2014_notebook.nb].
This model is described in the article:
Effects of IL-1β-Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms.
Palmér R, Nyman E, Penney M, Marley A, Cedersund G, Agoram B.
CPT Pharmacometrics Syst Pharmacol. 2014 Jun 11;3:e118.
Abstract:
Recent clinical studies suggest sustained treatment effects of interleukin-1β (IL-1β)-blocking therapies in type 2 diabetes mellitus. The underlying mechanisms of these effects, however, remain underexplored. Using a quantitative systems pharmacology modeling approach, we combined ex vivo data of IL-1β effects on β-cell function and turnover with a disease progression model of the long-term interactions between insulin, glucose, and β-cell mass in type 2 diabetes mellitus. We then simulated treatment effects of the IL-1 receptor antagonist anakinra. The result was a substantial and partly sustained symptomatic improvement in β-cell function, and hence also in HbA1C, fasting plasma glucose, and proinsulin-insulin ratio, and a small increase in β-cell mass. We propose that improved β-cell function, rather than mass, is likely to explain the main IL-1β-blocking effects seen in current clinical data, but that improved β-cell mass might result in disease-modifying effects not clearly distinguishable until >1 year after treatment.
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Vijayalakshmi Chelliah 
