In Vitro Sugar Interference Testing With Amperometric Glucose Oxidase Sensors.
continuous glucose monitors
enzyme kinetics
glucose oxidase
glucose sensors
in vitro testing
interferences
Journal
Journal of diabetes science and technology
ISSN: 1932-2968
Titre abrégé: J Diabetes Sci Technol
Pays: United States
ID NLM: 101306166
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
pubmed:
4
8
2018
medline:
25
4
2020
entrez:
4
8
2018
Statut:
ppublish
Résumé
Electrochemical enzymatic glucose sensors are intended to measure blood or interstitial fluid glucose concentrations. One class of these glucose sensors are continuous glucose monitors (CGMs), indicated for tracking and trending of glucose concentrations in interstitial fluid and as an adjunct to blood glucose testing. Currently approved CGMs employ a glucose oxidase (GOx) electrochemical detection scheme. Potential interfering agents can impact the accuracy of results obtained by glucose sensors, including CGMs. Seven sugars, seven sugar alcohols, and three artificial sweeteners were in vitro screened for interference with amperometric glucose oxidase (GOx) sensors at concentrations greater than physiologic concentrations. Galactose was investigated further at physiologically relevant concentrations using a custom amperometric system. Furthermore, glucose and galactose calibration experiments were conducted to facilitate multiple enzyme kinetic analysis approaches (Michaelis-Menten and Hill equation) to understand the potential source and mechanism of interference from galactose. Under in vitro testing, except for galactose, xylose and mannose, all screened compounds exhibited interference bias, expressed in mean absolute relative difference (MARD), of ⩽ 20% even at concentrations significantly higher than normal physiologic concentrations. Galactose exhibited, CGM-dependent, MARD of 47-72% and was subjected to further testing. The highest recorded mean relative difference (MRD) was 6.9 ± 1.3% when testing physiologically relevant galactose concentrations (0.1-10 mg/dL). Enzyme kinetic analysis provided calculations of maximum reaction rates ( Under the conditions of in vitro screening, 14 of the 17 compounds did not exhibit measuarable interference. Galactose exhibited the highest interference during screening, but did not substantially interfere with CGMs under the conditions of in vitro testing at physiologically relevant concentrations. Enzyme kinetic analysis conducted with galactose supported the notion that (1) the reactivity of GOx enzyme toward nonglucose sugars and (2) the presence of enzymatic impurities (such as galactose oxidase) are two potential sources for sugar interference with GOx glucose sensors, and thus, should be considered during device development.
Sections du résumé
BACKGROUND
Electrochemical enzymatic glucose sensors are intended to measure blood or interstitial fluid glucose concentrations. One class of these glucose sensors are continuous glucose monitors (CGMs), indicated for tracking and trending of glucose concentrations in interstitial fluid and as an adjunct to blood glucose testing. Currently approved CGMs employ a glucose oxidase (GOx) electrochemical detection scheme. Potential interfering agents can impact the accuracy of results obtained by glucose sensors, including CGMs.
METHODS
Seven sugars, seven sugar alcohols, and three artificial sweeteners were in vitro screened for interference with amperometric glucose oxidase (GOx) sensors at concentrations greater than physiologic concentrations. Galactose was investigated further at physiologically relevant concentrations using a custom amperometric system. Furthermore, glucose and galactose calibration experiments were conducted to facilitate multiple enzyme kinetic analysis approaches (Michaelis-Menten and Hill equation) to understand the potential source and mechanism of interference from galactose.
RESULTS
Under in vitro testing, except for galactose, xylose and mannose, all screened compounds exhibited interference bias, expressed in mean absolute relative difference (MARD), of ⩽ 20% even at concentrations significantly higher than normal physiologic concentrations. Galactose exhibited, CGM-dependent, MARD of 47-72% and was subjected to further testing. The highest recorded mean relative difference (MRD) was 6.9 ± 1.3% when testing physiologically relevant galactose concentrations (0.1-10 mg/dL). Enzyme kinetic analysis provided calculations of maximum reaction rates (
CONCLUSION
Under the conditions of in vitro screening, 14 of the 17 compounds did not exhibit measuarable interference. Galactose exhibited the highest interference during screening, but did not substantially interfere with CGMs under the conditions of in vitro testing at physiologically relevant concentrations. Enzyme kinetic analysis conducted with galactose supported the notion that (1) the reactivity of GOx enzyme toward nonglucose sugars and (2) the presence of enzymatic impurities (such as galactose oxidase) are two potential sources for sugar interference with GOx glucose sensors, and thus, should be considered during device development.
Identifiants
pubmed: 30073864
doi: 10.1177/1932296818791538
pmc: PMC6313278
doi:
Substances chimiques
Blood Glucose
0
Sugars
0
Glucose Oxidase
EC 1.1.3.4
Glucose
IY9XDZ35W2
Galactose
X2RN3Q8DNE
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
82-95Références
Metabolism. 1970 Jan;19(1):24-34
pubmed: 5410660
Biosens Bioelectron. 2015 Aug 15;70:411-7
pubmed: 25845333
J Diabetes Sci Technol. 2010 Mar 01;4(2):404-18
pubmed: 20307402
Biomaterials. 2003 Aug;24(17):2965-73
pubmed: 12742736
Diabetes. 2002 Sep;51(9):2742-8
pubmed: 12196467
Analyst. 2012 Dec 21;137(24):5785-91
pubmed: 23096254
Diabetes Care. 2010 Apr;33(4):728-9
pubmed: 20351227
Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S280-5
pubmed: 8933644
Diabetes Care. 2008 Jun;31(6):1160-4
pubmed: 18339974
Int J Biochem Cell Biol. 2005 Apr;37(4):731-50
pubmed: 15694834
Mol Cell Biochem. 1973 May 11;1(1):127-33
pubmed: 4807807
Nat Protoc. 2010 Feb;5(2):267-81
pubmed: 20134427
Diabetes Care. 2005 May;28(5):1231-9
pubmed: 15855600
Diabetes Res Clin Pract. 2012 Jun;96(3):294-305
pubmed: 22209014
Biochem J. 1948;42(2):221-9
pubmed: 16748271
Biochem J. 1974 Jun;139(3):715-20
pubmed: 4854723
Arch Biochem Biophys. 1960 Dec;91:230-4
pubmed: 13681372
Am J Clin Pathol. 2000 Jan;113(1):75-86
pubmed: 10631860
J Am Chem Soc. 2011 Dec 7;133(48):19262-5
pubmed: 22050076
Chem Rev. 2008 Feb;108(2):814-25
pubmed: 18154363
Pharmacotherapy. 2007 Sep;27(9):1313-21
pubmed: 17723085
Appl Biochem Biotechnol. 1987 Feb;14(1):37-47
pubmed: 3592653
Res Exp Med (Berl). 1976 May 15;167(2):127-38
pubmed: 981805
Yale J Biol Med. 1956 Dec;29(3):335-60
pubmed: 13409929
Anal Chem. 1976 Oct;48(12):1679-86
pubmed: 970629
Nature. 1959 Oct 24;184:1296-8
pubmed: 14402470
Clin Chim Acta. 1972 Apr;38(1):221-30
pubmed: 5031782
N Engl J Med. 2008 Oct 2;359(14):1464-76
pubmed: 18779236
J Diabetes Sci Technol. 2010 Mar 01;4(2):391-403
pubmed: 20307401
Medicine (Baltimore). 1990 May;69(3):153-9
pubmed: 2111870
Diabetes Technol Ther. 2016 Feb;18 Suppl 2:S243-7
pubmed: 26784129
J Phys Chem B. 2013 Jun 13;117(23):6980-9
pubmed: 23682574
Klin Wochenschr. 1986 Mar 17;64(6):265-9
pubmed: 3520129
Diabetes Technol Ther. 2009 Jun;11 Suppl 1:S17-24
pubmed: 19469674
Stroke. 1992 Sep;23(9):1276-9
pubmed: 1519282
FASEB J. 1997 Sep;11(11):835-41
pubmed: 9285481
J Neurosurg. 1975 Feb;42(2):226-8
pubmed: 163300
J Pharmacol Toxicol Methods. 2015 Jan-Feb;71:68-76
pubmed: 25157754
Biochem J. 1932;26(5):1406-21
pubmed: 16744959
Diabetes. 1984 Jan;33(1):97-100
pubmed: 6360771
Diabetes Technol Ther. 2009 Jun;11 Suppl 1:S11-6
pubmed: 19469670
Appl Environ Microbiol. 1998 Apr;64(4):1405-11
pubmed: 9546178
Diabet Med. 2011 Apr;28(4):386-94
pubmed: 21392060
Anal Biochem. 2004 Jun 1;329(1):85-90
pubmed: 15136170
J Clin Invest. 1963 Aug;42:1300-12
pubmed: 14057858
J Diabetes Sci Technol. 2012 Sep 01;6(5):1172-81
pubmed: 23063044
Comput Methods Programs Biomed. 2013 Jan;109(1):26-31
pubmed: 23021091
J Biol Chem. 1964 Nov;239:3927-34
pubmed: 14257628
Appl Biochem Biotechnol. 2010 Nov;162(6):1669-77
pubmed: 20339954