Role of diabetes and nitric oxide release duration on analytical performance of in vivo glucose biosensors

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 DESCRIPTION: The objective of this project is to study the analytical performance benefits of nitric oxide (NO)-releasing percutaneously implanted glucose sensors in a diabetic swine model as a function of NO-release duration. Continuous glucose monitoring (CGM) devices with superior usability (i.e., for immediate use and extended duration) would greatly increase the ability of those afflicted with diabetes to successfully manage their disease. We have demonstrated in a non-diabetic (i.e., healthy) swine model that NO- releasing sensor membranes both lessen the FBR and facilitate improved analytical sensor performance up to 10 days-the longest duration evaluated. However, CGM devices are intended for diabetic use and longer implantation periods would improve device utility/value. The variance in FBR and in vivo sensor performance among healthy and diabetic subjects is currently unknown but likely large due to impaired physiology and lower endogenous NO production. We hypothesize that the improvements in FBR and sensor performance that we have observed via exogenous (i.e., polymeric) NO release in healthy animals will be even greater in diabetic subjects. Through our work, we will study the influence of extended NO release on tissue biocompatibility and sensor performance as a function of diabetes. In this respect, we will generate new knowledge on how diabetes influences the FBR and in vivo sensor performance.