Roe Glucose Conc in Different Blood Compartments 2005

Glucose concentration difference
between arterial, capillary, and

venous blood
Roe J.N., Glucose concentration difference between arterial, capillary, and venous blood, 2005
Glucose concentration difference between arterial,
capillary, and venous blood
Jeffrey N. Roe, Ph.D.
3212 Vera Cruz Drive, San Ramon, CA 94583
Jeffnroe1@gmail.com
Abstract
A person with diabetes can choose from a number of home diagnostic test systems that measure glucose in
blood collected from a wide range of body sites. Questions have arisen about blood glucose concentration
comparability when blood was collected from capillary beds within different body site and how those
values relate to venous and arterial blood glucose. This paper reviews three physiological areas that can
alter a blood glucose reading from one blood compartment to another. In doing so, it attempts to clarify
how glucose concentration might differ in various blood samples. It also increases familiarity with
physiological parameters that affect glucose levels and possible problems with the analytical method used
to measure glucose. This should lead to better use of the available technology and help supply the most
clinically accurate glucose reading for the patient.
Keywords: arterial, venous, capillary, blood, glucose, oxygen, flow
Introduction
Three of the major factors that influence glucose test results are the type of chemical
analysis used for the test, the type of sample analyzed (whole blood verses plasma), and
the source of the blood (venous, capillary, or arterial)[1]. Home glucose monitoring has
traditionally relied on a drop of capillary blood from the finger, but off-finger capillary
sites are now being used and questions have arisen about their comparability.
Until recently, capillary blood from a fingerstick was the standard sample used in home
glucose monitoring. Occasionally, a blood sample from the earlobe or heel (infant
monitoring) was also used. Capillary samples from the finger or ear lobe have been
closely associated with arterial blood values, i.e., their glucose and oxygen properties are
more similar to arterial blood values than venous blood values [2,3]. However, even with
fingerstick blood, concerns have been expressed about the variation in finger sampling
technique 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 test
sample, i.e., too much squeezing or 'milking' of the fingertip to produce a drop of blood
may cause inaccuracies from either excess tissue fluid or hemolysis.
With the newest self-monitoring of blood glucose (SMBG) systems, capillary blood
samples from sites other than the fingertips (forearm, upper arm, palm of the hand, calf or
thigh) are used to measure glucose. These different locations must deal with the blood
variation concerns of the finger plus address the spatial and temporal heterogeneity of the
local cutaneous blood flow. It has been claimed that forearm capillary blood samples are
more similar to venous blood values than arterial blood values. Specifically, a
TheraSense™ FreeStyle™ test strip package insert states:
"Blood glucose in forearms and fingertips is not always the same…. FreeStyle
arm measurements, on average, are slightly lower than FreeStyle finger
measurements. The difference is similar in magnitude to the difference generally
observed 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 blood
glucose levels has neither been supported nor disproved in the literature.
This paper reviews three physiological areas that can alter a blood glucose reading from
one blood compartment to another. In doing so, it attempts to clarify how glucose
concentration might differ in various blood samples. It also increases familiarity with
physiological parameters that affect glucose levels and possible problems with the
analytical method used to measure glucose. This should lead to better use of the
available 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 is
being consumed by the body
Glucose diffuses through the capillaries and is consumed by the cells, so arterial glucose
concentration (the capillaries' source) should be higher than venous glucose concentration
(the capillaries' drain) unless capillary diffusion or muscle glucose consumption has been
stopped. 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/dL
lower 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 capillary
blood samples can exceed those in concurrently drawn venous samples. A typically
quoted value is up to 80 mg/dL difference between venous and fingerstick capillary blood
glucose 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 blood
is usually employed for laboratory analysis and is preferable in diabetes testing [6].
However, because of the widespread use of SMBG instruments, fingerstick capillary
blood samples have also become a standard. Fingerstick capillary blood has been shown
to be predominantly arterial [7] and so approximates the concentration of arterial blood.
Somogyi compared the glucose content of blood samples simultaneously drawn from the
femoral 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 the
arterial and venous glucose levels, and so should indicate whether fingerstick capillary
blood was predominantly arterial, venous, or a combination of the two. The
discrepancies between arterial and fingerstick capillary blood were less than 1 mg/dL for
all three subjects studied and seemed to justify the substitution of fingerstick capillary for
arterial blood glucose.
Somogyi also studied the difference between fingerstick capillary and venous glucose
levels during the fasting state on 100 healthy individuals (fasting for 10-14 hours). The
average fasting glucose value in fingerstick capillary blood samples was 89 mg/dL (78 -
97 mg/dL) with the average venous blood glucose value 5 mg/dL lower (84 mg/dL).
Averages can be misleading as the capillary-venous blood glucose difference did vary
widely among subjects. Differences between the fasting fingerstick capillary and venous
blood glucose levels ranged from 1 mg/dL to 7 mg/dL in 93% of the patients studied;
however, the fasting fingerstick capillary glucose values were 10 to 13 mg/dL higher than
venous glucose in 3% of the healthy individuals studied. For all 100 individuals, the
fingerstick capillary (paper assumed this to be arterial) blood glucose was always higher
than the venous blood glucose in line with the fact that cells continually assimilate blood
sugar. Hence the concentration of glucose inevitably decreases during the passage of
blood through the tissue. The study noted that the magnitude of the fingerstick capillary
(paper assumed this to be arterial) to venous blood glucose difference was not a
characteristic of the individual as the value would vary from day to day in a healthy
person, and it did not correlate to the fasting blood glucose value over the concentration
range studied.
In the same study, both venous and fingerstick capillary blood glucose values were
followed for a period of 4 hours in 44 healthy individuals that had ingested a 100-gram
glucose load. As shown in Figure 1, a substantial increase in the fingerstick capillary to
venous blood glucose difference were measured after an oral administration of glucose,
and this difference remained consistently higher than the initial fasting level until the
blood glucose returned to the fasting blood glucose level. The paper also found that the
larger the glucose load ingested, the higher the glucose peaks, and the greater the
maximal difference between the fingerstick capillary (paper assumed this to be arterial)
blood glucose level and the venous blood glucose level.
Arterial - venous glucose difference

100 gram oral glucose load
160
140
glucose (mg/dl)
120 Arterial
100 venous
80
60
0 1 2 3 4
time (hours)
Figure 1: The average arterial and venous blood glucose levels from 44 healthy individuals after a 100-
gram glucose load was ingested at time t=0. Fingerstick capillary blood glucose was measured in place of
arterial blood glucose after the two were shown to be equivalent.
4
A study by Liu measured arterial, fingerstick capillary, and venous blood samples from
six healthy males for oxygen saturation and glucose [8]. Each subject's right hand was
placed in a warm air box at 55-60 degrees C to determine if warm air would arterialize
the 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 saturation
measured in venous blood on a nonheated hand was 80%. The oxygen saturation
measured in the heated 'arterialized' venous blood was 94% or approximately 3% below
the average arterial value. Glucose levels also showed equilibration between the two
blood compartments with heating. The difference between fasting arterial glucose levels
and 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 oxygen
saturation between the two blood supplies. The difference between the arterial glucose
levels and 'arterialized' venous glucose levels obtained by heating the hand averaged less
than 2 mg/dL difference, and this glucose difference had a low correlation with the
differences in oxygen saturation between the two blood supplies.
The difference between capillary and venous blood in the postprandial state is due to
muscles removing more glucose from the blood than the liver in the presence of adequate
insulin action [6]. Absolute values of glucose uptake into body organs should follow the
organs metabolism and, in general, the higher an organ’s metabolism, the greater the
blood flow. Table 1 shows the blood flow to different organs and tissues under basal
conditions and gives an indication of their glucose needs. While inactive muscle
constitutes between 30-40 percent of the total body mass it requires only 15% of the
blood flow; however, during heavy exercise, muscle blood flow can increase as much as
20-fold to handle the increased metabolic activity [9]. As more blood is shifted to the
muscle, less blood goes to the tissues where it is not needed at the moment. During
exercise 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 local
blood flow allows the workload on the heart to be minimized while controlling the body’s
temperature and maintaining sufficient nutrients at critical tissue sites.
mL/minute mL/minute/100 % of total blood

grams flow
Brain 700 50 14
Heart 200 70 4
Kidneys 1100 360 22
Liver 1350 95 27
Muscle (inactive) 750 4 15
Bone 250 3 5
Skin (cool weather) 300 3 6
Table 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 most
of the available glucose, the epidermis layer of the skin also has a very high metabolic
activity and thus must have a high rate of glucose assimilation. The entire epidermis
completely 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 arterial
to 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 on
the sensitivity of the tissue to insulin, the circulating insulin level and the local blood
flow. Diabetics may have various degrees of peripheral insulin resistance or various
blood insulin levels or both, so a single patient’s nonfasting difference may not be seen in
other 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 so
closely correlated that most studies refer to arterial glucose measurements even if they
measure fingerstick capillary samples. When studies are performed with the patient under
fasting conditions, glucose levels in fingerstick capillary blood gives reliable quantitative
estimates of the venous glucose concentration as determined in the laboratory for most
patients. 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 venous
value may be anywhere from 2% lower during fasting to 26% lower within one hour after
a glucose load.
Unfortunately, empirical conversion factors have been applied to generate equivalent

glucose values for different blood sample compartments without adequate data to show
equivalence. One such conversion is that fingerstick capillary blood has a glucose
concentration that is 7-8% higher than the concurrently drawn venous concentration [11].
Others have presented charts showing the equivalence of venous and capillary glucose
levels 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 differences
between capillary and venous blood glucose values are too great to allow for a
meaningful transformation to be applied [13,14]. It can be reasonably concluded that there
is no simple conversion factor available to explain differences between glucose values in
the various blood compartments.
2. Glucose test values may not match because the body is consuming oxygen
Like glucose concentration, the oxygenation of venous blood is dependent on three main
factors: the oxygen saturation of arterial blood, the oxygen consumption of the tissue
drained by the vein concerned, and the rate of blood flow through the tissue. Oxygen
sensors measure the partial pressure or tension (pO2) of oxygen, and this is simply the
saturated density of free oxygen in blood.
The analytical methods that measure for glucose must be capable of dealing with oxygen
variation in the blood sample. However, some SMBG meters have been shown to be
sensitive to the large oxygen variation seen between fingerstick capillary (arterial) and
venous blood samples, and there are warnings in the package inserts against venous blood
use. Many analytical procedures are used to measure blood glucose but the most
common techniques are enzymatic. Enzymes commonly used in commercial test strips
are 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 oxygen
dependence problem in certain measurement systems. Electrochemical measurement
combined with glucose oxidase involves a mediator to transfer electrons between the
electrodes. The mediator attempts to replace oxygen in the reaction sequence. This
makes oxygen in the blood sample a competitor in the reaction and produces varying
results with varying oxygen concentrations (oxygen dependence). A Glucometer™
Elite™ test strip labeling stated: "A venous whole blood sample usually reads higher
than a (fingerstick) capillary sample from the same person (approximately 7% higher on
average with normal glucose samples) due to the unique electrochemical properties of the
test 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% lower
pO2 values [15]. A similar situation exists with some optical reflectance methods.
Generally, atmospheric oxygen is sufficient to meet the glucose oxidase reaction
requirements, but different test strip design can block the diffusion of oxygen to the
reaction site. To get around poor oxygen diffusion, a dye system has been utilized that
essentially takes the place of oxygen in the reaction. This replacement gives very fast
color development, but the oxygen content in the sample competes with the intended
reactant in the oxidation reaction creating oxygen dependence. Commercial analyzers
attempt to circumvent oxygen effects by pre-dilution of the sample into an oxygenated
buffer. Instruments that use a glucose oxidase reaction include optical measurement
devices OneTouch™ SureStep™, AccuChek™ Easy™ system, AccuChek Instant™
system and electrochemical measurement devices Glucometer Elite, and the laboratory
systems Beckman™ Glucose Analyzer and YSI™ Glucose Analyzer [16].
Glucose dehydrogenase can be made oxygen independent when it is combined with a

cofactor called pyrroloquiniline quinone (PQQ). Using this enzyme combination
effectively eliminates oxygen competition and enables the use of venous or arterial
samples where extremes of pO2 may occur. The trade-off is reduced specificity for
glucose in that it also detects maltose, galactose, and metabolites of maltodextrins. There
is also reduced operational stability when compared to glucose oxidase. The
electrochemical measurements by the AccuChek Advantage™ system and TheraSense
FreeStyle previously used this reaction mechanism [16], but due to maltose reactions they
have been changed.
Hexokinase combined with glucose-6-phosphate dehydrogenase also avoids oxygen

dependence, but the test strip is inherently more sensitive to heat and moisture, and
therefore special attention is paid to packaging. The Bayer™ Encore™ product uses this
mechanism [16].
Glucose comparison studies between arterial, capillary, and venous blood must consider
the significant differences in oxygen tension between the blood compartments when
using analytical systems that are oxygen dependent. Ideally, the effect of pO2 needs to
be examined by monitoring oxygen concentrations and determining if a correlation exists
for 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 forearm
The first two sections in this paper (glucose consumption and oxygen variation) concern
physiological parameters that would lead to a bias between glucose test results taken
simultaneously from two different blood compartments during either fasting or the meal
cycle.
A third physiological parameter that would cause glucose in one blood compartment to
lag or lead another is flow or circulation problems in a capillary bed. Many medical and
physical conditions can affect capillary blood flow with the problem being either
systemic or localized. Localized variations in blood flow associated with the capillary
beds would be a major contributing factor to erroneous comparison data between two
capillary blood supplies such as within the finger and forearm. A localized variation in
blood flow would also be a contributing factor in glucose differences measured within
capillary, arterial, and venous blood.
Blood flow to skin capillary beds is controlled by two major mechanisms: autonomic
nerve control of metarteriole and muscle control of capillaries through a precapillary
sphincter. The metarteriole is a preferential shunt around the capillary bed that directly
connects the arteriole to the venule and is under the control of the nervous system. In the
skin, opening or closing of these shunts is important in heat regulation of the body, and
the blood flow in these shunts does not participate in transfer of gases, nutrients, or
wastes. The precapillary sphincter is a band of smooth muscle at the junction of each
capillary vessel and arteriole. These sphincters regulate the amount of blood that enters
into the capillary bed, and as a result, blood does not flow continuously through the
capillaries, but intermittently in a series of pulses. This alteration of blood flow through
the capillaries is termed vasomotion. Vasomotion is a subtle and esoteric concept that can
globally result in lower blood flow. The frequency of vasomotion translates into more or
less flow. With these phenomena in mind, only an average rate of blood flow, capillary
pressure, and transfer of substances can be discussed. These average functions are in
reality the functions of literally billions of individual capillaries, each operating
intermittently in response to the local conditions of the tissue. This physiological
temporal variation in flow has also been described as regular rhythmic changes in flux
that 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) vasodilators
regulated by the rate of tissue metabolism or 2) lack of nutrient availability [9]. As an
example, a local drop in pO2 is the most important factor in the lack of nutrient theory
because oxygen is usually the rate-limiting metabolite delivered by the blood. As
explained by Guyton and Hall [9]:
“Because smooth muscle requires oxygen to remain contracted, one might
assume that the strength of contraction of the sphincters would increase
with an increase in oxygen concentration. Consequently, when the oxygen
concentration in the tissue rises above a certain level, the pre-capillary and
metarteriole sphincters presumably would close until the tissue cells
consume the excess oxygen. But when the excess oxygen is gone and the
oxygen concentration then falls low enough, the sphincters would open
once more to begin the cycle again.”
Closed capillaries provide a reserve flow capacity and can open quickly in response to
local conditions such as higher metabolic rates, a fall in pO2 or a fall in glucose when
additional flow is required. Additionally, the amplitude of blood flow can also be
sensitive to external stimuli such as ambient temperature and pain, and internal stimuli
such 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 the
consuming 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 only
20% - 30% of capillaries are normally open [18]. As an example, it is possible that only
70% of the forearm capillaries are flowing normally at any one time, and 30% have
slower-moving blood that is being depleted of glucose and oxygen by diffusion into the
cellular space. Lancing into such a location would produce glucose readings lower than
both arterial and venous blood glucose since more glucose consumption would occur in
areas with no flow. If the measurement technique were oxygen sensitive, then the
measurement would also be lower because of oxygen consumption by the surrounding
tissue. Ideally, blood collection from sites such as the forearm and thigh should target a
highly perfused capillary bed, and either compensate for or be independent of temporal
changes in blood flow. Research papers have not been found that investigate how
glucose levels vary under these situations. Two published studies focusing on other
measurement parameters noted that the capillary glucose level lags behind the venous
level in returning to normal [3,19]. In both these papers, a discernible lag was noted but no
explanation was attempted.
Amira Medical™ conducted a time-based study measuring venous, fingerstick capillary,

and forearm capillary blood glucose to determine if forearm capillary blood glucose
values more closely follow fingerstick or venous blood. Ten individuals (5 type-1 and 5
type-2) were tested first under fasting conditions and then after ingestion of a 75-gram
glucose load. Venous and capillary glucose values were monitored for a period of up to
five hours. A 75-gram glucose load was chosen because it is standard in routine
screening for diabetes and is more sensitive than blood glucose determinations after a
meal high in carbohydrate or a mixed meal of carbohydrate and protein. After a mixed
meal, postprandial insulin levels are higher and blood glucose levels are lower than after
a glucose load since glucose and amino acids potentiate each other with respect to insulin
release [6]. It is possible that the amount of glucose time lag between blood compartments
is 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 forearm
capillary blood sample, and a single fingerstick capillary sample were collected within a
10-minute window and measured with the AtLast blood glucose system. A Glucometer
Elite 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 not
graphed in the data sets to avoid clutter. Samples were drawn after an overnight fast at
10-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. At
the 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 blood
glucose analyzer. All blood samples were obtained from the subject while they were
seated. A lag in glucose values over time were calculated using a peak-to-peak method.
This was accomplished by fitting each blood compartment’s glucose values to a 6th order
polynomial, determining the polynomials peak and comparing the peak times for venous,
fingerstick, and forearm. The fingerstick capillary blood was collected from each subject
an average of 0.8 minutes after the venous blood and the forearm capillary blood was
collected from each subject an average of 3 minutes after the venous blood. This should
be kept in mind when reviewing the data because these time lags were not subtracted
from 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-2
diabetic). These three graphs represent the range of time lags seen in the data. Using
fingerstick blood glucose as the marker for the peak time lag, venous blood glucose
lagged 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 blood
leading fingerstick blood). Also, forearm blood glucose lagged fingerstick blood glucose
by 28 minutes, 43 minutes, and 8 minutes for subjects #1, #5, and #7 respectively. YSI
blood glucose measurements confirmed the accuracy of the AtLast blood glucose
measurements at the beginning, middle and end of the tests. When the peak time lags for
all 10 subjects were averaged, venous blood glucose lagged fingerstick blood glucose by
4.9 minutes on average and forearm blood glucose lagged fingerstick blood glucose by
16.2 minutes on average.
10
Subject #1
400
mean venous
AtLast (mg/dL)
350
mean hct. corr.

venous YSI
glucose (mg/dL)
glucose (mg/dL)
300
FS AtLast
Glucose (mg/dL)
250
mean hct corr. FS

glucose (mg/dL)
200
arm blood AtLast

Glucose (mg/dL)
150
8:00 9:00 10:00 11:00 12:00 13:00 14:00 15:00
time
Subject #5
400
mean venous
AtLast (mg/dL)
350
mean hct. corr.

venous YSI
300 glucose (mg/dL)
glucose (mg/dL)
FS AtLast
250 Glucose (mg/dL)
200
mean hct corr.
FS glucose
(mg/dL)
150
arm blood
AtLast Glucose
(mg/dL)
100
9:00 10:00 11:00 12:00 13:00 14:00 15:00
time
11
Subject #7
300
mean venous
AtLast (mg/dL)
250
mean hct. corr.

venous YSI
glucose (mg/dL)
glucose (mg/dL)
200
FS AtLast
Glucose (mg/dL)
150
mean hct corr.

FS glucose
(mg/dL)
100
arm blood
AtLast Glucose
(mg/dL)
50
8:00 9:00 10:00 11:00 12:00 13:00 14:00
time
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 data
from all 10 subjects. Figure 3a shows the correlation between venous and forearm
capillary 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 between
fingerstick capillary and forearm capillary blood glucose measured with the AtLast blood
glucose system that has 73.2% of values in the A-region. For comparison, Figure 3c
shows a correlation between venous and fingerstick capillary blood glucose measured
with 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.
12
600
A 81.1% slope: 0.81
B 16.7% intercept: 38.29
550
C 0.0% Sy.x 29.6
D 2.2% R 0.919
forearm glucose / AtLast (mg/dL)
500 E 0.0% avg. bias (% ): 1.74
MPAE: 12.15
450 N: 228
400
350
300
250
200
150
100
50
0
0
100
200
300
400
500
600
venous glucose / AtLast (mg/dL)
600
A 73.2% slope: 0.77
550 B 24.6% intercept: 44.24
C 0.0% Sy.x 30.7
forearm glucose / AtLast (mg/dL)
500 D 2.2% R 0.913

E 0.0% avg. bias (% ): 1.70
MPAE: 14.93
450
N: 228
400
350
300
250
200
150
100
50
0
0
50
100
150
200
250
300
350
400
450
500
550
600
fingerstick glucose / AtLast (mg/dL)
13
600
A 89.0% slope: 1.00
550 B 10.1% intercept: 1.90
C 0.0% Sy.x 22.8
fingerstick glucose / AtLast (mg/dL)
500 D 0.9% R 0.966
E 0.0% avg. bias (% ): 1.17
450 MPAE: 9.29
N: 227
400
350
300
250
200
150
100
50
0
0
100
200
300
400
500
600
venous glucose / AtLast (mg/dL)
Figure 3: Glucose correlation between venous, fingerstick, and forearm blood compartments during rapidly
changing glucose levels. Each graph is compiled using data from all 10 subjects in the study.
The study concluded that there is a lag between forearm capillary blood glucose and both
venous and fingerstick capillary blood glucose. There is also significant variability in the
length of lag between people in the study group. It is hypothesized that low blood flow in
the forearm capillary bed is a contributing factor to the observed lag. The rate of glucose
consumption, oxygen consumption and insulin concentration could also be playing a role
in the effect, but their concentration variation will also correlate with low blood flow as
well as diffusion resistance in the capillaries. The correlation graphs indicate that venous
blood glucose is a better reference for forearm capillary glucose measurements in studies
that use nonfasting subjects. However, this is not because forearm capillary blood is
more like venous. Venous blood is 'down stream' from the capillaries and so better
reflects any temporal decreases in the flow from the multitude of capillaries that feed the
vein even as it is affected by the artery shunts and muscle glucose consumption.
Because local blood flow can be increased by either heat or injury, it may be possible to
minimize or eliminate delay times by enhancing circulation. Friction rubbing, resistive
heating, chemical heating, vibration, or repetitive lancing could increase local blood flow
and so minimize glucose variation between blood compartments. Unfortunately,
published data is not available on how any of these variables affect the lags between
blood compartments and what minimal stimulus would be needed for improvement.
14
3b. Glucose test values may not match because of low blood flow in the fingers
Another contributing parameter that combines flow restriction and diffusion can be found
in finger capillary blood, but in this physiological effect the flow stops almost
completely. To restate, glucose consumption in the capillary system goes up as the flow
decreases 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 down
blood flow to the peripheral tissue. In published cases of restricted blood flow to the
fingers, fingerstick capillary blood was not the clinically appropriate sample for
monitoring blood glucose.
Many papers have been found in this category that indicates glucose measurement
problems do occur. Shock or severe hypotension (systolic blood pressure of 80 mm Hg
or 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 results
from inadequate blood flow through the body resulting in limited delivery of oxygen and
nutrients 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 and
almost one third of patients were misidentified as hypoglycemic by the fingerstick
method; two of these patients were actually hyperglycemic [20]. All studies noted that
the test strip measurement was accurate when using venous blood and compared to a
venous laboratory measurement. Also, all studies recommended use of venous blood
when a glucose test strip was used to determine glucose in hypotensive patients.
The administration of vasoactive drugs can influence capillary flow independent of the
shock 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 the
intensive care unit, inhibits the glucose oxidase reaction on a test strip [23]. However,
since the above studies monitored glucose using the same instrument with both
fingerstick capillary and venous blood, the dopamine effect would only come into play if
there were a large dopamine concentration difference between the two blood
compartments. 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 a
factor in the study results although it would not affect their conclusions.
Fingerstick capillary blood may also not be the clinically appropriate sample for patients
in 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 specificity
of fingerstick capillary blood for detection of hypoglycemia were 75% and 38%
respectively; whereas, test strip analysis of venous blood correctly identified all
hypoglycemic patients (sensitivity of 100%), with no patients incorrectly categorized as
hypoglycemic (specificity 100%). An explanation for the low fingerstick glucose
readings was not found, but a combination of increased glucose use and decreased
peripheral blood flow was attributed to be the most likely contributor. This study also
concluded that test strip determination of blood glucose is reliable for cardiac arrest
patients only if done on a sample of venous blood.
15
The major discrepancy in these studies between venous and capillary blood glucose
measurements probably reflects continued glucose utilization by peripheral tissues in the
presence of vascular stasis. This is likely caused by peripheral vasoconstriction with
shunting of blood from the periphery and continued tissue glucose consumption. Neural
regulation of skin blood flow includes the presence of arteriovenous anastomoses, which
are highly innervated structures involved in thermoregulatory processes. These shunts
provide a low-resistance pathway for blood flow where large volumes of blood can be
partitioned 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 control
of these vessels such that there is increased shunt flow creating a deficit in skin blood
flow at the nutritive capillary level [25].
Peripheral vascular disease or poor peripheral flow is likely to occur in patients when
dehydrated, 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 be
compromised due to vasoconstriction from drug therapy, hypothermia, edema, diabetes,
peripheral vascular disease, cardiovascular disease, or even hemodilution from
cardiopulmonary bypass.
Conclusions
Simultaneous measurements of arterial and venous blood samples should produce
different glucose values in healthy people due to glucose utilization by peripheral tissues.
Unfortunately, the magnitude of this glucose difference cannot be predicted due to the
large number of variables that affect it. Since capillary blood has been expanded to refer
to blood collected from the finger, forearm, ear, heel, calf, and stomach, questions have
arisen if each of these is predominantly arterial or venous. Published studies have
justified equating arterial and fingerstick capillary glucose levels under most conditions
but no other capillary blood source has been equally studied.
Local, rhythmic changes of blood flux within capillary beds play a larger role in the
variation of forearm capillary blood glucose vs. fingerstick capillary blood glucose than
the differences between arterial and venous values. It is not to say that forearm capillary
is more like venous, but that the independent temporal changes in select capillary beds
affect the venous value because it is upstream. An attempt should be made for blood
analysis from sites such as the forearm to be either compensated for or to be made
independent of temporal changes in blood flow. That said, venous blood glucose is a
better reference for arm blood glucose than fingerstick capillary measurements. In the
time course data sets (Figure 3) where glucose excursions were induced by Glucola™ (75
grams of glucose), a reference to venous blood glucose produced 7.9% more values in the
A-region for the AtLast forearm capillary measurement than when compared with
fingerstick capillary samples.
Although it appears that blood flow problems may be linked to the variation between
forearm capillary glucose measurements and either arterial or venous blood glucose
16
measurements, there are a number of other physiological parameters that can affect a
glucose measurement from capillary blood sources. Ideally, it would be advisable to
standardize the analytical chemistry method used to measure glucose and the blood
compartment from which the sample is drawn, and to adopt a uniform method of blood
collection. Unfortunately, such a worldwide standardization would stifle research and
development into new, less painful glucose instruments since it would limit market
acceptance of any technology that did not meet these standards. Therefore it is necessary
to better understand the glucose variation in any biological fluid used to measure glucose
and how they compare to more traditional glucose measurements.
The three physiological parameters presented in this paper could all occur simultaneously
or one at a time. Glucose data collected from a single individual could show a bias only
on 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, blood
flow, 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 the
Liu paper that heating the skin 'arterialized' the venous blood. Both heat and vacuum
may stimulate the skin so that some of these physiological parameters are minimized, but
currently this hypothesis has not been proven. Published studies have narrowed the areas
needing further studies, but additional research is needed. It should remain an exciting
area of research for years to come.
Acknowledgements
I 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 Amira
Medical.
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Glucose concentration difference

between arterial, capillary, and

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

Arterial - venous glucose difference

mL/minute mL/minute/100 % of total blood

Unfortunately, empirical conversion factors have been applied to generate equivalent

Glucose dehydrogenase can be made oxygen independent when it is combined with a

Hexokinase combined with glucose-6-phosphate dehydrogenase also avoids oxygen

Amira Medical™ conducted a time-based study measuring venous, fingerstick capillary,

mean hct. corr.

mean hct corr. FS

arm blood AtLast

mean hct. corr.

mean hct. corr.

mean hct corr.

500 D 2.2% R 0.913

fingerstick glucose / AtLast (mg/dL)

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