Numerous research publications have demonstrated the benefits of continuous glucose monitoring for better glucose control and reduced glycated hemoglobin (HbA1c) levels; however, to improve efficacy, significant improvements in the performance of implanted glucose sensors are required. The proposed Phase 1 research is focused on developing a rapid, microsecond, minimally invasive, continuous glucose monitor that addresses many of the limitations of currently marketed Continuous Glucose Monitors (CGMs) including: the body's immune response also known as biofouling, dynamic range, sensor lag, and accuracy in the hypoglycemic range (<70 mg/dL). Included in the Specific Aims is the development of a new technology for measuring enzymatic reactions occurring on a microsecond scale that have not been described previously. In addition, this research will yield a better understanding of both chemical and electrochemical processes occurring within 20E of a biosensor surface. The results of this research will also yield a near instantaneous indication of the effects of the body's immune response on the sensor output, thus enabling error free in vivo glucose measurements with essentially zero sensor lag. This will reduce the overall lag-time associated with interstitial fluid glucose measurements; thereby, significantly improving accuracy. Inaccuracy has limited FDA pre-market approval of CGMs to adjunctive therapy to fingerstick monitoring. This means all readings from the CGM must be confirmed by fingerstick measurements prior to adjustments in insulin dosage or diet. In the long-term, for continuous glucose monitoring to gain wider consumer acceptance and reimbursement by Medicare and health Insurers, accuracy needs to be improved and the requirement for periodic re-calibration of CGM sensors reduced or eliminated. Successful completion of this proposed Phase 1 research will provide significant advances in continuous glucose monitoring technology that have the potential to resolve many of the accuracy and calibration issues faced by users. Furthermore, improved accuracy and the ability to correct for biofouling will provide additional efficacy data that health insurance providers are demanding for reimbursement, and bring the concept of the artificial pancreas one step closer to reality.
Public Health Relevance: The lack of sustained control and inadequate monitoring of glucose concentration to avoid glycemic excursions comes at a high cost to the national healthcare system, and has a demonstrated impact on disease progression and secondary complications for patients with diabetes and impaired glucose tolerance. Current 1st generation FDA approved continuous glucose monitoring (CGM) devices have gained limited or conditional acceptance by insulin dependent diabetics, regulatory agencies, and third- party insurance payers due to accuracy problems and the need for frequent recalibration. The micro- second sampling rate and signal processing algorithms of the proposed CGM system overcome existing technical limitations and provide a resolution of measurement and control on a scale orders of magnitude higher than current devices, thereby making the "closed loop" artificial pancreas a near-term reality.
Public Health Relevance Statement: PROJECT NARRATIVE The lack of sustained control and inadequate monitoring of glucose concentration to avoid glycemic excursions comes at a high cost to the national healthcare system, and has a demonstrated impact on disease progression and secondary complications for patients with diabetes and impaired glucose tolerance. Current 1st generation FDA approved continuous glucose monitoring (CGM) devices have gained limited or conditional acceptance by insulin dependent diabetics, regulatory agencies, and third- party insurance payers due to accuracy problems and the need for frequent recalibration. The micro- second sampling rate and signal processing algorithms of the proposed CGM system overcome existing technical limitations and provide a resolution of measurement and control on a scale orders of magnitude higher than current devices, thereby making the "closed loop" artificial pancreas a near-term reality.
NIH Spending Category: Bioengineering; Biotechnology; Diabetes
Project Terms: APAP; Acetamide, N-(4-hydroxyphenyl)-; Acetamidophenol; Acetaminophen; Acetominophen; Address; Algorithms; Applications Grants; Artificial Pancreas; Ascorbic Acid; Belief; Biochemical Reaction; Biosensor; Blood Coagulation Factor III; Blood Plasma; Bovine Species; CD142 Antigens; Calibration; Cattle; Cells; Chemicals; Clinical Protocols; Clinical Research; Clinical Study; Coagulation Factor III; Coagulin; Code; Coding System; Collaborations; Comment; Comment (PT); Comment [Publication Type]; Commentary; Commentary (PT); Computer Programs; Computer software; Consultations; Custom; D-Glucose; Data; Designing computer software; Development; Devices; Dextrose; Diabetes Mellitus; Diagnostic; Diet; Disease Progression; Doctor of Philosophy; Drug Formulations; Editorial Comment; Editorial Comment (PT); Electrodes; Electronics; Encapsulated; Endocrinologist; Environment; Enzymatic Reaction; Ethics Committees, Research; Evaluation; FDA approved; Factor III; Fibrin; Formulation; Formulations, Drug; Freezing; Fungi, Filamentous; Generations; Glomerular Procoagulant Activity; Glucose; Glycated Hemoglobins; Glycohemoglobin A; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Government; Grant Proposals; Grants, Applications; Hb A1; Hb A1a+b; Hb A1c; HbA1; HbA1c; Health; Health Insurance; Health Insurance for Aged and Disabled, Title 18; Health Insurance for Aged, Title 18; Health Insurance for Disabled Title 18; Healthcare Systems; Hemoglobin A(1); Hemoglobin, Glycosylated; Human; Human, General; Humulin R; Hydroxyacetanilide; Hypoglycemia; IRBs; Immune response; Implant; In Vitro; Institutional Review Boards; Insulin; Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine-; Insulin, Regular; Insurance; Insurance Carriers; Insurers; Intercellular Fluid; Interstitial Fluids; L-Ascorbic Acid; Lead; Length of Life; Longevity; Man (Taxonomy); Man, Modern; Marketing; Measurement; Measures; Mechanics; Medicare; Membrane; Methods; Microcid; Modification; Molds; Monitor; Msec; N-(4-Hydroxyphenyl)acetanilide; N-Acetyl-p-aminophenol; Needles; Noise; Novolin R; One Step; One-Step dentin bonding system; Output; PROV; Paracetamol; Patients; Pb element; Performance; Persons; Ph.D.; PhD; Phase; Physiologic pulse; Plasma; Preclinical Testing; Process; Prothrombinase; Provider; Publications; Published Comment; Pulse; Reading; Reporting; Research; Research Ethics Committees; Resistance; Resolution; Reticuloendothelial System, Serum, Plasma; Sampling; Scientific Publication; Serum, Plasma; Software; Software Design; Surface; System; System, LOINC Axis 4; Systems, Health Care; Technology; Testing; Thromboplastin; Time; Tissue Factor; Tissue Factor Procoagulant; Tissue Thromboplastin; Title 18; Universities; Urothromboplastin; V (voltage); VIT C; Vendor; Viewpoint; Viewpoint (PT); Vitamin C; Work; analog; aqueous; base; beta-D-Glucose[{..}]oxygen 1-oxidoreductase; blood glucose regulation; bovid; bovine; computer program/software; computerized data processing; cost; cow; data processing; design; designing; diabetes; diabetic; digital; dosage; electronic data; glucose control; glucose homeostasis; glucose meter; glucose monitor; glucose oxidase; glucose regulation; glucose sensor; health insurance for disabled; heavy metal Pb; heavy metal lead; hemoglobin A1c; host response; hypoglycemic; hypoglycemic episodes; immunoresponse; impaired glucose tolerance; improved; in vitro testing; in vivo; life span; lifespan; medical schools; membrane structure; millisecond; minimally invasive; monitoring device; new technology; p-Acetamidophenol; p-Hydroxyacetanilide; prototype; public health relevance; resistant; response; sensor; sensor (biological); signal processing; time interval; validation studies; voltage
