Analytical Interferences and Physiological Limitations of Blood Glucose Meters Ken Ervin
Published information n n Package inserts Review articles (partial list) q q q q 03162010 Boren and Clarke Tonyushkina and Nichols Pitkin and Rice Montagnana et al Wahl Dungan Arabadjief and Nichols Heller and Feldman n Specific articles (partial list) q q q q q Kimberly, et al Fiore and Delanghe Lyon, et al Kazmierczak and Catrou Goudable, et al Zheng, et al Vesper, et al Katelijne and Delanghe Tang, et al Ken Ervin Consulting Services
Package inserts address “Procedural limitations” n Sample related q n n n e. g. Hct, p. O 2, DKA, HHNK, etc. Endogenous compounds Exogenous compounds Environmental q q q 03162010 Temperature Humidity Altitude Ken Ervin Consulting Services
The limitations of a product are dependent upon the choice of technology to achieve the design goals. 03162010 Ken Ervin Consulting Services
BGM Design Goals Drive the specifications and choice of technology n n n Accurate and precise Highly specific *Stable at room temperature *Rapid test (use whole blood directly) *Very easy to use Small blood volume 03162010 n n *Inexpensive meter *Cal code strategy Low cost/test More recently q q q No p. O 2 dependence No maltose interference No hematocrit effect Ken Ervin Consulting Services
To meet the specifications, technologies are chosen for the measurement device and its method of production 03162010 Ken Ervin Consulting Services
BGM measurement based on combining technologies n Method of introducing sample to device q n Method to identify glucose in sample (specificity) q n Enzymatic reaction (GO, GDH, Hexokinase/G 6 PDH) Method to quantify glucose q n Most devices now rely on capillary action, sometimes in two directions Colorimetric Electrochemical Method of calibration Methods to assess performance of the test or correct results 03162010 Ken Ervin Consulting Services
Interferences and physiological limitations are related to choices of sample type and technology 03162010 Ken Ervin Consulting Services
Interferences result from n n Analyte specificity issues or Sample and environmental influences on the measurement reaction 03162010 Ken Ervin Consulting Services
Analyte specificity n Use of enzymes specific for glucose q q q 03162010 GO GDH Hexokinase/G 6 PDH Ken Ervin Consulting Services
Sample influences on measurement n Endogenous substances q q q n Uric acid Bilirubin Lipemia, Hemolysis Exogenous substances q q q 03162010 Acetominophen Ascorbate Maltose, Icodextrin metabolites Mannitol Dopamine Ken Ervin Consulting Services
Sample influences n DKA, HHNK q p. H and/or Viscosity n n 03162010 Hyperosmolar, flow effects Less water volume to reconstitute reagent Ken Ervin Consulting Services
Environmental influences n Analytical Variability q q q 03162010 Temperature Humidity Altitude (i. e. oxygen availability) Ken Ervin Consulting Services
Physiological limitations n Sample choice q Capillary, venous, or arterial n n n Actual concentrations are different and relationship may vary If capillary; hypotension, perfusion and other conditions such as Reynaud’s syndrome disturb normal relationship Alternate site time lag p. O 2 differences Hematocrit Smaller sample sizes increase the potential for residue to influence results 03162010 Ken Ervin Consulting Services
Some relevant examples n n How a p. O 2 dependence became a maltose interference Hematocrit effects 03162010 Ken Ervin Consulting Services
The p. O 2 effect glucose + O 2 + H 2 O GO H 2 O 2 + dye precursor glucose + med (ox) med (red) 03162010 GO Epot gluconic acid + H 2 O 2 HRPO (YSI and Beckman Glucose Analyzer) dye color + H 20 gluconolactone + med (red) e- + med (ox) Ken Ervin Consulting Services (colorimetric) (electrochemical)
How a p. O 2 interference became a maltose interference n Original methods based on glucose oxidase coupled to a colorimetric indicator system. q Oxygen available from atmosphere n n n Electrochemical methods used mediators q n blood removed by blotting, wiping etc. exposed to air during the reaction time Systems calibrated for capillary blood Oxygen would interfere competitively q Use of venous or arterial blood exacerbated this competition n n q 03162010 Venous reads higher; less 02 competition Arterial reads lower; more 02 competition p. O 2 effects generally greater at lower glucose concentrations Ken Ervin Consulting Services
How a p. O 2 interference became a maltose interference n Second Generation products q GO n n q 03162010 Open to atmospheric oxygen Oxygen blocked by windows or capillary design Hexokinase/G 6 PDH Ken Ervin Consulting Services
How a p. O 2 interference became a maltose interference n GDH-PQQ systems introduced to alleviate p. O 2 q q n However, GDH-PQQ less specific for glucose q n GDH reaction does not involve oxygen RT stable enzyme Recognizes maltose, galactose, xylose and other sugars with glucose moiety, with false elevation of glucose results. Recent versions of GDH with NAD or FAD cofactor are more specific and stable. 03162010 Ken Ervin Consulting Services
n For a rapid test, WB is preferable if not necessary Most systems now report “plasma equivalent” Systems are calibrated at normal hematocrit. WB sample hematocrits may vary significantly (~15 to >70) Glucose content of whole blood as compared to plasma is inversely related with hematocrit. Hematocrit effects n n 03162010 Ken Ervin Consulting Services
Hematocrit dependence Little method effect Greater method effect 03162010 Ken Ervin Consulting Services
Hematocrit effects n n n Hematocrit may influence access of plasma or diffusion of glucose to measurement system suppressing results. Hematocrit effects generally greater at higher glucose concentrations Hematocrit can be measured and corrected for q 03162010 Greater imprecision? Ken Ervin Consulting Services
In Conclusion n n Limitations and interferences are related to the particular technologies chosen. The unique goals of a BGM system make it unlikely they will ever completely match a lab based system. The evolution of BGM devices is a demonstration of achieving a balance between a high degree of performance with a rapid, more versatile, easy to use system. Using a WB sample and reporting plasma (unless corrected for) introduces a ± 6% error in the range 25 -65 hct. 03162010 Ken Ervin Consulting Services
03162010 Ken Ervin Consulting Services
03162010 Ken Ervin Consulting Services
03162010 Ken Ervin Consulting Services
03162010 Ken Ervin Consulting Services
03162010 Ken Ervin Consulting Services
03162010 Ken Ervin Consulting Services
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