Mathematical Models for Obesity-Induced Type 2 Diabetes Mellitus and Chronic Wound Healing - Project Summary
Aim: To develop a predictive mathematical model of obesity-induced diabetes and chronic wound that includes
a realistic representation of the main physiological factors that are correlated with high prevalence of type
1/type 2 diabetes, and that also take into account a more detailed process of glucose/glycogen exchange in the
liver.
The Need: Obesity is a risk factor for several diseases, two of which are diabetes and chronic wounds: 85%
of adult Americans with type 2 diabetes mellitus (T2DM) are overweight or obese, and 30% of obese adults
have the disease. Studies have identified causes, mechanisms and obesity-related glucose/glycogen exchange
factors which impair healing of dermal wounds; these factors have been represented by constant parameter so
far. The overall premises of this proposal is to focus on better understanding the role of these factor and
model them by variable functions.
The Opportunity: Recent work have identified four main factors that are correlated with the high prevalence
of type 1/type 2 diabetes, and which impair healing of dermal wounds in diabetes patients: D1 = excessive
production of glucagon, D2 = excessive production of leukotrient, D3 = decreased production of stromal cell-
derived factor-1, and D4 = insulin resistance. However, these work main deficiencies were to take the Di's as
constant parameters. To make this model predictive, one must derive the Di's based on the dynamics of
glucose associated with obesity. But since this dynamics is also associated with obesity-induced diabetes,
there is need to develop this aspect as well. Some initial work already begun in our lab in this regard, where
developed a mathematical model that includes the mechanisms of glucose transport from the blood to the
liver,and from the liver to the blood, and explains how obesity is likely to lead to lead to T2DM, and used the
model to evaluate the efficacy of an anti-T2DM drug that also reduces weight. However, here again there are
some parameters that were taken as constants, and again, to be a predictive model, these parameters will need
to be dynamics.
The Impact: Success in this work will open up entirely new ways to design and analyze within-host mathe-
matical models in general, and those of glucose-insulin dynamical systems in health and in the case of obesity-
induced diabetic chronic wounds in particular. We anticipate direct practical applicability as our modeling
techniques could be replicated and our conclusions used as hypotheses for clinical trials. Hence, this project
offers a potential to reinvent the modeling of glucose-insulin dynamical system in obese-induced diabetic
chronic wounds by enhancing the quality of virtual patients development, necessary for assessing new
experimental or approved drugs. Moreover, the same concepts readily translate to a wide range of important
chronic infections/diseases such as cancers, hepatitis B virus, and osteoporosis among others.
