Roe Glucose Conc in Different Blood Compartments 2005

8/8/2019 Roe Glucose Conc in Different Blood Compartments 2005

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Roe J.N., Glucose concentration difference between arterial, capillary, and venous blood, 2005

Glucose concentration differencebetween arterial, capillary, and

venous blood


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Glucose concentration difference between arterial,capillary, and venous blood

Jeffrey N. Roe, Ph.D.

3212 Vera Cruz Drive, San Ramon, CA [email protected]

AbstractA person with diabetes can choose from a number of home diagnostic test systems that measure glucose inblood collected from a wide range of body sites. Questions have arisen about blood glucose concentrationcomparability when blood was collected from capillary beds within different body site and how thosevalues relate to venous and arterial blood glucose. This paper reviews three physiological areas that canalter a blood glucose reading from one blood compartment to another. In doing so, it attempts to clarifyhow glucose concentration might differ in various blood samples. It also increases familiarity withphysiological parameters that affect glucose levels and possible problems with the analytical method usedto measure glucose. This should lead to better use of the available technology and help supply the mostclinically accurate glucose reading for the patient.

Keywords: arterial, venous, capillary, blood, glucose, oxygen, flow

IntroductionThree of the major factors that influence glucose test results are the type of chemicalanalysis used for the test, the type of sample analyzed (whole blood verses plasma), andthe source of the blood (venous, capillary, or arterial) [1] . Home glucose monitoring hastraditionally relied on a drop of capillary blood from the finger, but off-finger capillarysites are now being used and questions have arisen about their comparability.

Until recently, capillary blood from a fingerstick was the standard sample used in homeglucose monitoring. Occasionally, a blood sample from the earlobe or heel (infantmonitoring) was also used. Capillary samples from the finger or ear lobe have beenclosely associated with arterial blood values, i.e., their glucose and oxygen properties aremore similar to arterial blood values than venous blood values [2,3] . However, even withfingerstick blood, concerns have been expressed about the variation in finger samplingtechnique and changes in peripheral blood flow as these may alter the composition of capillary blood. The main worry that has been expressed is contamination of the testsample, i.e., too much squeezing or 'milking' of the fingertip to produce a drop of bloodmay cause inaccuracies from either excess tissue fluid or hemolysis.

With the newest self-monitoring of blood glucose (SMBG) systems, capillary bloodsamples from sites other than the fingertips (forearm, upper arm, palm of the hand, calf orthigh) are used to measure glucose. These different locations must deal with the bloodvariation concerns of the finger plus address the spatial and temporal heterogeneity of thelocal cutaneous blood flow. It has been claimed that forearm capillary blood samples aremore similar to venous blood values than arterial blood values. Specifically, aTheraSense FreeStyle test strip package insert states:


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"Blood glucose in forearms and fingertips is not always the same. FreeStylearm measurements, on average, are slightly lower than FreeStyle fingermeasurements. The difference is similar in magnitude to the difference generallyobserved between capillary finger measurements and venous measurement [4]Venous whole blood results are about 7% lower than a capillary sample from the

same person with normal glucose levels."

However, an empirical conversion factor between forearm capillary and venous bloodglucose levels has neither been supported nor disproved in the literature.

This paper reviews three physiological areas that can alter a blood glucose reading fromone blood compartment to another. In doing so, it attempts to clarify how glucoseconcentration might differ in various blood samples. It also increases familiarity withphysiological parameters that affect glucose levels and possible problems with theanalytical method used to measure glucose. This should lead to better use of theavailable technology and help supply the most clinically accurate glucose reading for the

patient.1. Glucose test values may not match with different blood samples because glucose isbeing consumed by the bodyGlucose diffuses through the capillaries and is consumed by the cells, so arterial glucoseconcentration (the capillaries' source) should be higher than venous glucose concentration(the capillaries' drain) unless capillary diffusion or muscle glucose consumption has beenstopped. It has been shown that in fasting subjects the glucose levels in arterial, capillary,and venous samples are practically the same (venous glucose is generally 2-5 mg/dLlower than fingerstick capillary or arterial blood glucose) [5,6] . It is only after meals,when glucose uptake in the periphery is rapid, that glucose levels in fingerstick capillaryblood samples can exceed those in concurrently drawn venous samples. A typicallyquoted value is up to 80 mg/dL difference between venous and fingerstick capillary bloodglucose values one hour after ingestion of 100 grams of glucose [2] .

Current literature has attempted to determine exactly how glucose levels in venous,arterial and fingerstick capillary blood vary so comparisons can be made. Venous bloodis usually employed for laboratory analysis and is preferable in diabetes testing [6] .However, because of the widespread use of SMBG instruments, fingerstick capillaryblood samples have also become a standard. Fingerstick capillary blood has been shownto be predominantly arterial [7] and so approximates the concentration of arterial blood.Somogyi compared the glucose content of blood samples simultaneously drawn from thefemoral artery and the fingertip of non-diabetics one-hour after ingestion of 50 grams of glucose. The ingested glucose would produce a substantial difference between thearterial and venous glucose levels, and so should indicate whether fingerstick capillaryblood was predominantly arterial, venous, or a combination of the two. Thediscrepancies between arterial and fingerstick capillary blood were less than 1 mg/dL forall three subjects studied and seemed to justify the substitution of fingerstick capillary forarterial blood glucose.


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A study by Liu measured arterial, fingerstick capillary, and venous blood samples fromsix healthy males for oxygen saturation and glucose [8] . Each subject's right hand wasplaced in a warm air box at 55-60 degrees C to determine if warm air would arterializethe venous blood obtained from a cannula inserted into the dorsal right-hand vein. The

oxygen saturation measured in the arterial blood was 97%. The oxygen saturationmeasured in venous blood on a nonheated hand was 80%. The oxygen saturationmeasured in the heated 'arterialized' venous blood was 94% or approximately 3% belowthe average arterial value. Glucose levels also showed equilibration between the twoblood compartments with heating. The difference between fasting arterial glucose levelsand venous glucose levels with no heating of the hand ranged between 4-9 mg/dL (6%-9%), and this glucose difference significantly correlated with the differences in oxygensaturation between the two blood supplies. The difference between the arterial glucoselevels and 'arterialized' venous glucose levels obtained by heating the hand averaged lessthan 2 mg/dL difference, and this glucose difference had a low correlation with thedifferences in oxygen saturation between the two blood supplies.

The difference between capillary and venous blood in the postprandial state is due tomuscles removing more glucose from the blood than the liver in the presence of adequateinsulin action [6]. Absolute values of glucose uptake into body organs should follow theorgans metabolism and, in general, the higher an organs metabolism, the greater theblood flow. Table 1 shows the blood flow to different organs and tissues under basalconditions and gives an indication of their glucose needs. While inactive muscleconstitutes between 30-40 percent of the total body mass it requires only 15% of theblood flow; however, during heavy exercise, muscle blood flow can increase as much as20-fold to handle the increased metabolic activity [9] . As more blood is shifted to themuscle, less blood goes to the tissues where it is not needed at the moment. Duringexercise the flow to skin is initially reduced but is later increased to get rid of excess heat.This action confirms a fundamental principle of circulatory function: controlling localblood flow allows the workload on the heart to be minimized while controlling the bodystemperature and maintaining sufficient nutrients at critical tissue sites.

mL/minute mL/minute/100grams

% of total blood flow

Brain 700 50 14Heart 200 70 4Kidneys 1100 360 22Liver 1350 95 27

Muscle (inactive) 750 4 15Bone 250 3 5Skin (cool weather) 300 3 6Table 1: Blood flow and blood flow by weight to different organs and tissues under basal conditions [9].

Although key organs such as the liver, kidney and muscle during exercise consume mostof the available glucose, the epidermis layer of the skin also has a very high metabolic


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activity and thus must have a high rate of glucose assimilation. The entire epidermiscompletely renews itself in a period varying from 45 to 75 days [10] .

It has been shown that a lack of insulin (in the de-pancreatized animal) shows an arterialto venous glucose difference that is extremely small and that injection of insulin produces

an increase in this difference[3]

. As such, glucose uptake by the tissue is dependent onthe sensitivity of the tissue to insulin, the circulating insulin level and the local bloodflow. Diabetics may have various degrees of peripheral insulin resistance or variousblood insulin levels or both, so a single patients nonfasting difference may not be seen inother patients. The nonfasting difference will depend on meal size, meal content, time of sample collection, and individual patient variability.

In summary, glucose levels in arterial and fingerstick capillary blood have been soclosely correlated that most studies refer to arterial glucose measurements even if theymeasure fingerstick capillary samples. When studies are performed with the patient underfasting conditions, glucose levels in fingerstick capillary blood gives reliable quantitative

estimates of the venous glucose concentration as determined in the laboratory for mostpatients. However, when the patients are under a glucose load the venous and fingerstick capillary glucose levels diverge in a similar but unpredictable manner where the venousvalue may be anywhere from 2% lower during fasting to 26% lower within one hour aftera glucose load.

Unfortunately, empirical conversion factors have been applied to generate equivalentglucose values for different blood sample compartments without adequate data to showequivalence. One such conversion is that fingerstick capillary blood has a glucoseconcentration that is 7-8% higher than the concurrently drawn venous concentration [11] .Others have presented charts showing the equivalence of venous and capillary glucoselevels that differ between 0% to 13% depending on the glucose level [12] . The validity of these conversion factors has been called into question since individual differencesbetween capillary and venous blood glucose values are too great to allow for ameaningful transformation to be applied [13,14] . It can be reasonably concluded that thereis no simple conversion factor available to explain differences between glucose values inthe various blood compartments.

2. Glucose test values may not match because the body is consuming oxygenLike glucose concentration, the oxygenation of venous blood is dependent on three mainfactors: the oxygen saturation of arterial blood, the oxygen consumption of the tissuedrained by the vein concerned, and the rate of blood flow through the tissue. Oxygensensors measure the partial pressure or tension (pO2) of oxygen, and this is simply thesaturated density of free oxygen in blood.

The analytical methods that measure for glucose must be capable of dealing with oxygenvariation in the blood sample. However, some SMBG meters have been shown to besensitive to the large oxygen variation seen between fingerstick capillary (arterial) andvenous blood samples, and there are warnings in the package inserts against venous blooduse. Many analytical procedures are used to measure blood glucose but the most


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common techniques are enzymatic. Enzymes commonly used in commercial test stripsare glucose oxidase, glucose dehydrogenase, or hexokinase combined with glucose-6-phosphate dehydrogenase.

Glucose oxidase has historically been the preferred enzyme because of its excellent

specificity for glucose, good room temperature stability, and relatively low cost.However, the reaction requires an adequate oxygen supply, and this leads to an oxygendependence problem in certain measurement systems. Electrochemical measurementcombined with glucose oxidase involves a mediator to transfer electrons between theelectrodes. The mediator attempts to replace oxygen in the reaction sequence. Thismakes oxygen in the blood sample a competitor in the reaction and produces varyingresults with varying oxygen concentrations (oxygen dependence). A GlucometerElite test strip labeling stated: "A venous whole blood sample usually reads higherthan a (fingerstick) capillary sample from the same person (approximately 7% higher onaverage with normal glucose samples) due to the unique electrochemical properties of thetest strip." Electrochemical test strips that are calibrated using fingerstick capillary blood

can read up to 30% higher when tested with venous blood because of its 50-60% lowerpO2 values [15] . A similar situation exists with some optical reflectance methods.Generally, atmospheric oxygen is sufficient to meet the glucose oxidase reactionrequirements, but different test strip design can block the diffusion of oxygen to thereaction site. To get around poor oxygen diffusion, a dye system has been utilized thatessentially takes the place of oxygen in the reaction. This replacement gives very fastcolor development, but the oxygen content in the sample competes with the intendedreactant in the oxidation reaction creating oxygen dependence. Commercial analyzersattempt to circumvent oxygen effects by pre-dilution of the sample into an oxygenatedbuffer. Instruments that use a glucose oxidase reaction include optical measurementdevices OneTouch SureStep, AccuChek Easy system, AccuChek Instantsystem and electrochemical measurement devices Glucometer Elite, and the laboratorysystems Beckman Glucose Analyzer and YSI Glucose Analyzer [16] .

Glucose dehydrogenase can be made oxygen independent when it is combined with acofactor called pyrroloquiniline quinone (PQQ). Using this enzyme combinationeffectively eliminates oxygen competition and enables the use of venous or arterialsamples where extremes of pO2 may occur. The trade-off is reduced specificity forglucose in that it also detects maltose, galactose, and metabolites of maltodextrins. Thereis also reduced operational stability when compared to glucose oxidase. Theelectrochemical measurements by the AccuChek Advantage system and TheraSenseFreeStyle previously used this reaction mechanism [16] , but due to maltose reactions theyhave been changed.

Hexokinase combined with glucose-6-phosphate dehydrogenase also avoids oxygendependence, but the test strip is inherently more sensitive to heat and moisture, andtherefore special attention is paid to packaging. The Bayer Encore product uses thismechanism [16] .


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Glucose comparison studies between arterial, capillary, and venous blood must considerthe significant differences in oxygen tension between the blood compartments whenusing analytical systems that are oxygen dependent. Ideally, the effect of pO2 needs tobe examined by monitoring oxygen concentrations and determining if a correlation existsfor glucose. Only Liu's paper discussed earlier has been found to adequately perform this

task [8]

.

3a. Glucose test values may not match because of low blood flow in the forearmThe first two sections in this paper (glucose consumption and oxygen variation) concernphysiological parameters that would lead to a bias between glucose test results takensimultaneously from two different blood compartments during either fasting or the mealcycle.

A third physiological parameter that would cause glucose in one blood compartment tolag or lead another is flow or circulation problems in a capillary bed. Many medical andphysical conditions can affect capillary blood flow with the problem being either

systemic or localized. Localized variations in blood flow associated with the capillarybeds would be a major contributing factor to erroneous comparison data between twocapillary blood supplies such as within the finger and forearm. A localized variation inblood flow would also be a contributing factor in glucose differences measured withincapillary, arterial, and venous blood.

Blood flow to skin capillary beds is controlled by two major mechanisms: autonomicnerve control of metarteriole and muscle control of capillaries through a precapillarysphincter. The metarteriole is a preferential shunt around the capillary bed that directlyconnects the arteriole to the venule and is under the control of the nervous system. In theskin, opening or closing of these shunts is important in heat regulation of the body, andthe blood flow in these shunts does not participate in transfer of gases, nutrients, orwastes. The precapillary sphincter is a band of smooth muscle at the junction of eachcapillary vessel and arteriole. These sphincters regulate the amount of blood that entersinto the capillary bed, and as a result, blood does not flow continuously through thecapillaries, but intermittently in a series of pulses. This alteration of blood flow throughthe capillaries is termed vasomotion. Vasomotion is a subtle and esoteric concept that canglobally result in lower blood flow. The frequency of vasomotion translates into more orless flow. With these phenomena in mind, only an average rate of blood flow, capillarypressure, and transfer of substances can be discussed. These average functions are inreality the functions of literally billions of individual capillaries, each operatingintermittently in response to the local conditions of the tissue. This physiologicaltemporal variation in flow has also been described as regular rhythmic changes in fluxthat occur with periods that range from approximately one second to several minutes [17] .

Two basic theories for the regulation of local blood flow involve either 1) vasodilatorsregulated by the rate of tissue metabolism or 2) lack of nutrient availability [9] . As anexample, a local drop in pO2 is the most important factor in the lack of nutrient theorybecause oxygen is usually the rate-limiting metabolite delivered by the blood. Asexplained by Guyton and Hall [9] :


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Because smooth muscle requires oxygen to remain contracted, one mightassume that the strength of contraction of the sphincters would increasewith an increase in oxygen concentration. Consequently, when the oxygenconcentration in the tissue rises above a certain level, the pre-capillary and

metarteriole sphincters presumably would close until the tissue cellsconsume the excess oxygen. But when the excess oxygen is gone and theoxygen concentration then falls low enough, the sphincters would openonce more to begin the cycle again.

Closed capillaries provide a reserve flow capacity and can open quickly in response tolocal conditions such as higher metabolic rates, a fall in pO2 or a fall in glucose whenadditional flow is required. Additionally, the amplitude of blood flow can also besensitive to external stimuli such as ambient temperature and pain, and internal stimulisuch as exercise and psychological stress.

Lower flow in the capillaries will lead to greater exchange of nutrients and metabolites.Simplistically, a drop of blood moving slowly will have more time to lose glucose to theconsuming tissue compared to a drop of blood moving quickly. In tissues like the heart,all capillaries are normally open to perfusion, but in skeletal muscle and intestine only20% - 30% of capillaries are normally open [18] . As an example, it is possible that only70% of the forearm capillaries are flowing normally at any one time, and 30% haveslower-moving blood that is being depleted of glucose and oxygen by diffusion into thecellular space. Lancing into such a location would produce glucose readings lower thanboth arterial and venous blood glucose since more glucose consumption would occur inareas with no flow. If the measurement technique were oxygen sensitive, then themeasurement would also be lower because of oxygen consumption by the surroundingtissue. Ideally, blood collection from sites such as the forearm and thigh should target ahighly perfused capillary bed, and either compensate for or be independent of temporalchanges in blood flow. Research papers have not been found that investigate howglucose levels vary under these situations. Two published studies focusing on othermeasurement parameters noted that the capillary glucose level lags behind the venouslevel in returning to normal [3,19] . In both these papers, a discernible lag was noted but noexplanation was attempted.

Amira Medical conducted a time-based study measuring venous, fingerstick capillary,and forearm capillary blood glucose to determine if forearm capillary blood glucosevalues more closely follow fingerstick or venous blood. Ten individuals (5 type-1 and 5type-2) were tested first under fasting conditions and then after ingestion of a 75-gramglucose load. Venous and capillary glucose values were monitored for a period of up tofive hours. A 75-gram glucose load was chosen because it is standard in routinescreening for diabetes and is more sensitive than blood glucose determinations after ameal high in carbohydrate or a mixed meal of carbohydrate and protein. After a mixedmeal, postprandial insulin levels are higher and blood glucose levels are lower than aftera glucose load since glucose and amino acids potentiate each other with respect to insulin


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release [6] . It is possible that the amount of glucose time lag between blood compartmentsis dependent on the glucose load, but it was not studied in this experiment.

A set of blood samples consisting of duplicate venous blood samples, a single forearmcapillary blood sample, and a single fingerstick capillary sample were collected within a

10-minute window and measured with the AtLast blood glucose system. A GlucometerElite blood glucose system was also used in the study to measure venous and fingerstick capillary blood in duplicate but so closely matches the AtLast data that it is notgraphed in the data sets to avoid clutter. Samples were drawn after an overnight fast at10-minute intervals for 30 minutes under the fasting condition. After the ingestion of glucose, blood samples were again drawn at 10-minute intervals for up to five hours. Atthe beginning, middle, and end of the five-hour experiment, a venous and a fingerstick capillary sample were also collected and measured in duplicate on a laboratory YSI bloodglucose analyzer. All blood samples were obtained from the subject while they wereseated. A lag in glucose values over time were calculated using a peak-to-peak method.This was accomplished by fitting each blood compartments glucose values to a 6 th order

polynomial, determining the polynomials peak and comparing the peak times for venous,fingerstick, and forearm. The fingerstick capillary blood was collected from each subjectan average of 0.8 minutes after the venous blood and the forearm capillary blood wascollected from each subject an average of 3 minutes after the venous blood. This shouldbe kept in mind when reviewing the data because these time lags were not subtractedfrom the peak lag time data presented in this paper.

Figures 2 shows the blood glucose variation achieved with three of the 10 subjects(Subject #1, a type-1 diabetic; Subject #5, a type-2 diabetic and Subject #7, a type-2diabetic). These three graphs represent the range of time lags seen in the data. Usingfingerstick blood glucose as the marker for the peak time lag, venous blood glucoselagged fingerstick blood glucose by 0 minutes, 6 minutes and -4 minutes for subjects #1,#5, and #7 respectively (a negative number means the peak fit shows venous bloodleading fingerstick blood). Also, forearm blood glucose lagged fingerstick blood glucoseby 28 minutes, 43 minutes, and 8 minutes for subjects #1, #5, and #7 respectively. YSIblood glucose measurements confirmed the accuracy of the AtLast blood glucosemeasurements at the beginning, middle and end of the tests. When the peak time lags forall 10 subjects were averaged, venous blood glucose lagged fingerstick blood glucose by4.9 minutes on average and forearm blood glucose lagged fingerstick blood glucose by16.2 minutes on average.


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Subject #1

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mean hct. corr.venous YSIglucose (mg/dL)

FS AtLastGlucose (mg/dL)

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Subject #7

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Figure 2 :Glucose values over time from venous, fingerstick and forearm blood compartments. Each graph

shows data from a single subject.

Figure 3 shows three correlation graphs for rapidly changing glucose values using datafrom all 10 subjects. Figure 3a shows the correlation between venous and forearmcapillary blood glucose measured with the AtLast blood glucose system that has 81.1% of

values in the A-region utilizing Clarke Error Grid. Figure 3b shows a correlation betweenfingerstick capillary and forearm capillary blood glucose measured with the AtLast bloodglucose system that has 73.2% of values in the A-region. For comparison, Figure 3cshows a correlation between venous and fingerstick capillary blood glucose measuredwith the AtLast blood glucose system that has 89.0% of values in the A-region. Data of steady-state glucose values (not shown) taken under fasting conditions gave >97.0% of values in the A-region for the three graphs.


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0

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A 81.1% slope: 0.81B 16.7% intercept: 38.29C 0.0% Sy.x 29.6D 2.2% R 0.919E 0.0% avg. bias (%): 1.74

MPAE : 12.15

N: 228

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A 73.2% slope: 0.77B 24.6% in tercept: 44.24C 0.0% Sy.x 30.7D 2.2% R 0.913E 0.0% avg. bias (%): 1.70

MPAE: 14.93N: 228


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3b. Glucose test values may not match because of low blood flow in the fingersAnother contributing parameter that combines flow restriction and diffusion can be foundin finger capillary blood, but in this physiological effect the flow stops almostcompletely. To restate, glucose consumption in the capillary system goes up as the flowdecreases so low flow capillary blood samples can be depleted of their glucose supply. A

familiar example would be hypothermia where long exposure to cold weather shuts downblood flow to the peripheral tissue. In published cases of restricted blood flow to thefingers, fingerstick capillary blood was not the clinically appropriate sample formonitoring blood glucose.

Many papers have been found in this category that indicates glucose measurementproblems do occur. Shock or severe hypotension (systolic blood pressure of 80 mm Hgor less) are examples of clinical conditions that adversely affect the measurement of glucose in fingerstick capillary blood [20-22] . It is generally accepted that shock resultsfrom inadequate blood flow through the body resulting in limited delivery of oxygen andnutrients to the tissue cells. In the most complete study, only 36% of hypotensive

patients had a fingerstick capillary glucose within +/- 20 % of the laboratory value andalmost one third of patients were misidentified as hypoglycemic by the fingerstick method; two of these patients were actually hyperglycemic [20] . All studies noted thatthe test strip measurement was accurate when using venous blood and compared to avenous laboratory measurement. Also, all studies recommended use of venous bloodwhen a glucose test strip was used to determine glucose in hypotensive patients.

The administration of vasoactive drugs can influence capillary flow independent of theshock state. Not all patients in the two studies were on vasoactive drugs but up to 72%were. It has been documented that dopamine, a common vasopressor drug used in theintensive care unit, inhibits the glucose oxidase reaction on a test strip [23] . However,since the above studies monitored glucose using the same instrument with bothfingerstick capillary and venous blood, the dopamine effect would only come into play if there were a large dopamine concentration difference between the two bloodcompartments. One study [20] was unable to show any relationship between the degree of fingerstick capillary glucose reduction and the use of intravenous dopamine.Unfortunately, dopamine blood concentration was not measured so this could still be afactor in the study results although it would not affect their conclusions.

Fingerstick capillary blood may also not be the clinically appropriate sample for patientsin cardiac arrest, as a study showed it to be relatively nonspecific for identification of hypoglycemia in this patient population [24] . In this study, the sensitivity and specificityof fingerstick capillary blood for detection of hypoglycemia were 75% and 38%respectively; whereas, test strip analysis of venous blood correctly identified allhypoglycemic patients (sensitivity of 100%), with no patients incorrectly categorized ashypoglycemic (specificity 100%). An explanation for the low fingerstick glucosereadings was not found, but a combination of increased glucose use and decreasedperipheral blood flow was attributed to be the most likely contributor. This study alsoconcluded that test strip determination of blood glucose is reliable for cardiac arrestpatients only if done on a sample of venous blood.


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The major discrepancy in these studies between venous and capillary blood glucosemeasurements probably reflects continued glucose utilization by peripheral tissues in thepresence of vascular stasis. This is likely caused by peripheral vasoconstriction withshunting of blood from the periphery and continued tissue glucose consumption. Neural

regulation of skin blood flow includes the presence of arteriovenous anastomoses, whichare highly innervated structures involved in thermoregulatory processes. These shuntsprovide a low-resistance pathway for blood flow where large volumes of blood can bepartitioned to a superficial venous plexus, largely bypassing the nutritive capillaries of the skin. An attractive hypothesis is that diabetes may result in the loss of neural controlof these vessels such that there is increased shunt flow creating a deficit in skin bloodflow at the nutritive capillary level [25] .

Peripheral vascular disease or poor peripheral flow is likely to occur in patients whendehydrated, hypovolaemic, hypotensive or suffer from small vessel disease [5] .Hyperosmolar hyperglycemia is another example of clinical conditions that adversely

affect the measurement of glucose in fingerstick capillary blood. Circulation may also becompromised due to vasoconstriction from drug therapy, hypothermia, edema, diabetes,peripheral vascular disease, cardiovascular disease, or even hemodilution fromcardiopulmonary bypass.

ConclusionsSimultaneous measurements of arterial and venous blood samples should producedifferent glucose values in healthy people due to glucose utilization by peripheral tissues.Unfortunately, the magnitude of this glucose difference cannot be predicted due to thelarge number of variables that affect it. Since capillary blood has been expanded to referto blood collected from the finger, forearm, ear, heel, calf, and stomach, questions havearisen if each of these is predominantly arterial or venous. Published studies have

justified equating arterial and fingerstick capillary glucose levels under most conditionsbut no other capillary blood source has been equally studied.

Local, rhythmic changes of blood flux within capillary beds play a larger role in thevariation of forearm capillary blood glucose vs. fingerstick capillary blood glucose thanthe differences between arterial and venous values. It is not to say that forearm capillaryis more like venous, but that the independent temporal changes in select capillary bedsaffect the venous value because it is upstream. An attempt should be made for bloodanalysis from sites such as the forearm to be either compensated for or to be madeindependent of temporal changes in blood flow. That said, venous blood glucose is abetter reference for arm blood glucose than fingerstick capillary measurements. In thetime course data sets (Figure 3) where glucose excursions were induced by Glucola (75grams of glucose), a reference to venous blood glucose produced 7.9% more values in theA-region for the AtLast forearm capillary measurement than when compared withfingerstick capillary samples.

Although it appears that blood flow problems may be linked to the variation betweenforearm capillary glucose measurements and either arterial or venous blood glucose


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measurements, there are a number of other physiological parameters that can affect aglucose measurement from capillary blood sources. Ideally, it would be advisable tostandardize the analytical chemistry method used to measure glucose and the bloodcompartment from which the sample is drawn, and to adopt a uniform method of bloodcollection. Unfortunately, such a worldwide standardization would stifle research and

development into new, less painful glucose instruments since it would limit marketacceptance of any technology that did not meet these standards. Therefore it is necessaryto better understand the glucose variation in any biological fluid used to measure glucoseand how they compare to more traditional glucose measurements.

The three physiological parameters presented in this paper could all occur simultaneouslyor one at a time. Glucose data collected from a single individual could show a bias onlyon the first blood measurement and a bias with lag on the second only a short time later.In comprehensive studies, other parameters will need to be measured (oxygen, bloodflow, and others) to separate these factors and better understand glucose physiology.Additional studies will help clarify when the current glucose measurement technology

will be most accurate and when it might be clinically unacceptable. It was noted in theLiu paper that heating the skin 'arterialized' the venous blood. Both heat and vacuummay stimulate the skin so that some of these physiological parameters are minimized, butcurrently this hypothesis has not been proven. Published studies have narrowed the areasneeding further studies, but additional research is needed. It should remain an excitingarea of research for years to come.

AcknowledgementsI wish to thank Uwe Kraemer for substantive discussions and Phil Stout, Michelle Delli-Santi, Gina Moss, and Anne Callahan with help in collecting the data sets at AmiraMedical.

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4. Burtis CA, Ashwood ER (editors): Tietz Textbook of Clinical Chemistry , 2nd Editon, W.B. Saunders Company, 1994;959.

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the Accu-Chek III, Progress in Cardiovascular Nursing 1995;10(4):27-30.8. Liu D, Moberg E, Kollind M, Lins PE, Adamson U and MacDonald IA: Arterial,

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Roe Glucose Conc in Different Blood Compartments 2005