4.8 Article

Biomarker monitoring and long-acting insulin treatment in a stress model to facilitate personalized diabetic control

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 332, Issue -, Pages 21-28

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2021.02.013

Keywords

Insulin; Diabetes; pH; Lactate; Glucose; Microdialysis

Funding

  1. JDRF [2-SRA-2017-505-S-B]

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This study focuses on improving diabetes management by monitoring stress biomarkers, revealing that pH, lactate, and glucose levels changed more significantly under stress conditions, with long-acting insulin treatment shown to shorten these changes. Subcutaneous pH was identified as a sensitive stress biomarker for diabetic rats, emphasizing the importance of accurate glycemic control and the potential for personalized medicine through appropriate biomarker monitoring.
Diabetes is a chronic disease involving elevated blood glucose levels. Controlled insulin delivery is an ideal method to achieve glycemic control. However, glucose levels vary as a result of changes in the body?s physiological conditions resulting from different daily events, such as meals, exercise and stress. It is essential to develop and to monitor appropriate biomarkers for these natural physiological perturbations in order to achieve a holistic understanding of metabolic changes in diabetic patients to facilitate optimal glucose management and make possible personalized medicine for this very debilitating disease. The novel aspects of the current research include the combination of the tail suspension stress animal model and microdialysis for stress biomarker monitoring. A tail suspension test was optimized and used as a stress inducer for different groups of model rats (normal, untreated diabetic and insulin-treated diabetic rats). The levels of multiple metabolic analytes in the subcutaneous tissue were monitored continuously using subcutaneous microdialysis analysis. Different analytes, including pH, glucose and lactate were monitored and analyzed. Another important and original aspect of the reported work is that revelation that the pH, lactate and glucose levels increased under the stress conditions and the changes tended to be more pronounced in diabetic rats (both untreated and long-acting insulin-treated) compared to normal rats. Long-acting insulin treatment was shown to shorten the duration of the pH and glucose changes in response to stress when compared to the untreated diabetic rats. An additional novel aspect of the research is that subcutaneous pH was shown to be a sensitive stress biomarker for diabetic rats as pH changes rapidly after stress initiation. This research provides insight into the importance of accurate glycemic control and diabetes management for individual patients through highlighting stress management and appropriate biomarker monitoring, especially the value of combining pH and lactate monitoring with typical glucose monitoring. This research will pave the way for individualized medicine for diabetic patients through helping to obtain a holistic understanding of the various important biomarkers, rather than solely depending on glucose monitoring to determine appropriate insulin dosing.

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