Abstract:
The principal cause of hyperglycemia-mediated post-diabetic complications (PDCs) is -
oxidative stress (OS). Therefore, establishing a quantitative relationship between OS and
glycemic status (GS) of a diabetic individual could help in deciding how much and how long
OS should be controlled via external anti-glycemic treatment. To monitor serial changes in
OS (as measured by glutathione or GSH, an OS marker), a group of newly diagnosed type
2 diabetic patients kept on anti-diabetic treatment were followed for the period of 8 weeks.
A cluster analysis performed on the GSH values pooled from non-diabetics and diabetics
before and after therapy (0 and 8 weeks) show that GSH can be used to classify individuals
based upon their diabetic status, independently of glucose. That is, GSH can be an excellent
anti-oxidant to monitor along with glucose in defining diabetes status. Further, GSH
levels are found to be inversely correlated with the GS of diabetic individuals. We propose a
physiological minimal mathematical model to capture a quantal dose-response relationship
between GSH and glucose for each diabetic patient. Individualised diabetic GSH-glucose
curves are parameterised by: maximal glutathione level (Gtot), glucose concentration when
GSH is half maximal (v) and slope of the curve (k). Finally, to relax the assumptions imposed
in the physiological model, a statistical phenomenological model is proposed to capture
OS-GS trajectories in diabetic patients. We show that a phenomenological model is a statistically
better and simple alternative to the physiological minimal model. We propose that
individually parameterised GSH-glucose curves can be helpful in deciding optimal glucose
control strategies through which OS is maximally controlled. Thus, glucose targets can be
personalised based upon the OS state of an individual.
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