Ervin- Analytical Interferences and Physiological Limitations of BGM

8/6/2019 Ervin- Analytical Interferences and Physiological Limitations of BGM

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Analytical Interferences and

Physiological Limitations of

Blood Glucose Meters

diabetestechnology.org/

Ken Ervin


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03162010 Ken Ervin Consulting Services

Published information

Package inserts

Review articles (partiallist)

Boren and Clarke

Tonyushkinaand Nichols Pitkin and Rice

Montagnana et al

Wahl

Dungan

Arabadjiefand Nichols Hellerand Feldman

Specificarticles (partiallist)

Kimberly, et al

Fiore and Delanghe

Lyon, et al

Kazmierczakand Catrou

Goudable, et al

Zheng, et al

Vesper, et al

Katelijne and Delanghe Tang, et al

KRE1


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Slide 2

KRE1 So, just how do BGM systems using basically the same measurement tecchnology differ from laboratory methods?Ken Ervin, 2/25/2010


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The limitations of a product are

dependent upon the choice oftechnology to achieve the design goals.


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To meet the specifications,

technologies are chosen for themeasurement device and its method of

production


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Interferences and physiological

limitations are related to choices ofsample type and technology


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Interferences result from

Analyte specificity issues or

Sample and environmental influences on the

measurement reaction


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Analyte specificity

Use of enzymes specific forglucose

GO

GDH

Hexokinase/G6PDH


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Sample influences on measurement

Endogenous substances Uricacid

Bilirubin

Lipemia, Hemolysis

Exogenous substances Acetominophen

Ascorbate

Maltose, Icodextrin metabolites Mannitol

Dopamine


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Environmental influences

AnalyticalVariability

Temperature

Humidity

Altitude (i.e. oxygen availability)


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Physiological limitations

Sample choice

Capillary, venous, orarterial Actualconcentrations are different and relationship may vary

Ifcapillary; hypotension, perfusion and otherconditions suchas Reynauds syndrome disturb normal relationship

Alternate site time lag

pO2 differences

Hematocrit

Smaller sample sizes increase the potential for

residue to influence results


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Some relevant examples

How a pO2 dependence became a maltose

interference

Hematocrit effects


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The pO2

effect

glucose + O2 + H2Ogluconicacid + H2O2

GO

glucose + med (ox) gluconolactone + med (red)GO

H2O2 + dye precursor dye color + H20HRPO

(colorimetric)

(electrochemical)

med (red) e

-

+ med (ox)

Epot

(YSIand Beckman

Glucose Analyzer)


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How a pO2 interference became a

maltose interference Original methods based on glucose oxidase coupledto acolorimetric indicator system. Oxygen available from atmosphere

blood removed by blotting, wiping etc.

exposed to air during the reaction time

Electrochemical methods used mediators Systems calibrated forcapillary blood

Oxygen would interfere competitively Use of venous orarterialblood exacerbated this competition

Venous reads higher; less 02 competition

Arterial reads lower; more 02 competition

pO2 effects generally greaterat lowerglucose concentrations


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maltose interference Second Generation products

GO

Open to atmospheric oxygen

Oxygen blocked by windows orcapillary design Hexokinase/G6PDH


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maltose interference GDH-PQQ systems introduced to alleviate pO2

GDH reaction does not involve oxygen

RT stable enzyme

However, GDH-PQQless specific forglucose Recognizes maltose, galactose, xylose and other sugars

with glucose moiety, with false elevation ofglucose results.

Recent versions of GDH with NAD or FADcofactor

are more specificand stable.


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Hematocrit effects

Fora 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.

KRE2

KRE5


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Slide 20

KRE2 especially in a hospital situationKen Ervin, 3/2/2010

KRE5 insert hematocrit graph

Ken Ervin, 3/2/2010


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Hematocrit dependence

0

10

20

30

40

50

60

70

80

90

1st Qtr 2nd Qtr 3rd Qtr 4th Qtr

He ma to crit e ffe ct

-40

-30

-20

-10

0

10

20

30

40

0 20 40 60 80

H m c i

Bi

pl

Physiological effect

Littlemethod effect

Greatermethod effect


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Hematocrit effects

Hematocrit may influence access of plasma or

diffusion ofglucose to measurement system

suppressing results.

Hematocrit effects generally greaterat higherglucose concentrations

Hematocrit can be measured and corrected for

Greater imprecision?

KRE4


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Slide 22

KRE4 more important in diffusion based systems and short time framesKen Ervin, 3/2/2010


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In Conclusion

Limitations and interferences are related to theparticular technologies chosen.

The unique goals ofa BGM system make it unlikely

they will evercompletely match alabbased system. The evolution of BGM devices is a demonstration ofachievingabalance between a high degree ofperformance with a rapid, more versatile, easy touse system.

UsingaWB sample and reporting plasma (unlesscorrected for) introduces a 6% error in the range25-65 hct.

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Ervin- Analytical Interferences and Physiological Limitations of BGM