- Email: [email protected]
The ExacTech blood glucose testing system
Diabetes Research and Clinical Practice,
10 (1990) 85-90
85
Elsevier DIABET 00421
The ExacTech blood glucose testing system Kirsten Ohm Kyvik, .Jette Traulsen, Departments
Birgitte Reinholdt
of Medicine and Clinical Chemistry, Fredericia
and Anders Fwland
Hospital, Denmark
(Received 17 October 1989) (Revision received 29 March 1990) (Accepted 30 March 1990)
Summary The ExacTech system, a new device for home measurement of blood glucose was tested in the laboratory, in the out-patient clinic, and by diabetic patients. The system is based on an electrochemical principle, and consists of specially impregnated strips and a small, pencil-shaped meter. (1) Six meters were tested in the laboratory at blood glucose concentrations of 4, 10 and 20 mmol/l. Low coefficients of variation were found at 10 and 20 mmol/l, but those at 4 mmol/l were rather high (approximately 10%). Analysis of variances showed no difference in the between and the within variation of the meters. (2) The blood glucose concentrations of 50 consecutive out-patients were determined by the ExacTech system and a standard laboratory method. Correlation analysis showed an I value of 0.95 (P < 0.001). (3) The results obtained by 13 patients repeating the correlation experiment were in agreement with the second part of the study. The ExacTech system is very simple to operate by the patients, and can be recommended for home monitoring of blood glucose. Key words: Diabetes mellitus; Home monitoring
of blood glucose; Glucose meter
Introduction Home monitoring of blood glucose (HMBG) is recommended as a means to improve metabolic control in diabetes mellitus [ l-31. The most commonly used systems are based on reagent strips impregnated with glucose oxidase and a dye. The procedure includes timing, wiping and rinsing of the strip [ 1,4,5]. Less complicated systems have now been developed [ 6,7]. One new system is the Address for correspondence: Anders Freland, M.D., Department of Medicine, Fredericia Hospital, DK 7000 Fredericia, Denmark. 0168-8227/90/$03.50
0 1990 Elsevier Science Publishers
ExacTech blood glucose testing system based on an electrochemical reaction. We wanted to test the system both when used by skilled personnel and by patients. The protocol included three separate studies: (1) A laboratory investigation with repeated measurements at different blood glucose concentrations on a number of instruments operated by experienced laboratory technicians. (2) Comparison by correlation analysis of measurements on blood samples tested by the ExacTech system and a standard laboratory glucose dehydrogenase method. (3) Comparison by correlation analyses of
B.V. (Biomedical
Division)
measurements done by the patients at HMBG with the ExacTech system, and samples collected by the patients and later analysed in the laboratory. Finally, the patients were asked to answer a questionary on their opinion on the ExacTech system.
Materials and Methods The ExacTech system The ExacTech meter (Fig. 1) is 136 mm long, has a diameter of 15 mm, and the form of a pen. At one end there is an on/off switch, at the other a slit for the insertion of a reagent strip. On the side there is a digital display showing the BGC in mmol/l or mg/dl. The reagent area of the strips is impregnated with glucose oxidase, which catalyzes the conversion of the glucose of the blood specimen into glucuronic acid [ 81. The electrons generated by this process are transferred by a ferrocene mediator to the underlying electrodes [ 91. The current is proportional to the BGC of the test specimen. The result is shown on the display after 30 s. The meter is calibrated with a special test strip for each new batch of reagent strips. Two control solutions of low and high BGC are also available, permitting the patients to perform a quality control. At BGCs higher than 16 mmol/l (280 mg/dl), the display shows a request for checking the urine for ketone bodies. The patients Fifty patients with insulin-treated diabetes mellitus took part in the second section of the study.
They all attended the out-patient clinic of the Fredericia Hospital, Denmark. The participants were between 18 and 79 years old. No special inclusion or exclusion criteria were applied. Eighteen patients, aged 17-61 years, took part in section 3 of the study. They were all familiar with HMBG and with collecting blood samples in microvettesTM (for HbA,, determinations). Patients with known anaemia, polycythaemia, high values of s-urate, s-cholesterol, and s-triglycerides were excluded, as were patients with known abuse of salicylates. All patients accepted to participate on the basis of written and verbal information. The study was approved by the local ethical committee. Reference blood samples For part 2 of the study, samples of whole capillary blood for reference glucose estimations were collected in test tubes containing heparin and a haemolysing agent. The glucose content of the haemolysate is stable during 1 week at room temperature. For part 3 the blood was collected in small plastic vessels (microvettesTM, Sarstedt, F.R.G.). The microvettes contain sodium fluoride and heparin. The glucose concentration has been reported to be stable for 28 days [ lo]. Blood glucose was determined in the laboratory by a standard glucose dehydrogenase method (Cobas MiraTM, Merck). Study design (1) The laboratory study. Three samples of heparinized venous blood with BGCs of approximately 4, 10 and 20 mmol/l (72, 180 and 360 mg/dl) were measured with six ExacTech
CllP /
Fig. 1. The ExacTech blood glucose meter and reagent strips.
On/Off Button /
87
instruments. All reagent strips were from the same batch. Twenty-five ,ul of blood were used for each test. The button switch was activated immediately after application of the blood. Approximately 10 determinations were done at each BGC level on each meter, depending on the amount of blood available. (2) Comparison of BGCs measured by the ExacTech system and a standard method. Fifty
patients attending the out-patient clinic for their usual control were asked to participate. A drop of capillary blood from an ear lobe or a finger tip was used for measuring the BGC by the ExacTech system. A further 20 ~1 of blood from the same prick was collected in a test tube for analysis on the same day in the laboratory. Two of the authors did all the blood sampling and BGC measurements with the ExacTech system.
TABLE 1 Results of repeated Experiment A Pen No. No. of tests Max. value mmol/l Min. value mmol/l Mean value mmol/l SD. mmol/l C.V. z Analysis of variances Ratio between/within P value Experiment B Pen No. No. of tests Max. value mmol/l Min. value mmol/l Mean value mmol/l S.D. mmol/l C.V. ;, Analysis of variances Ratio between/within P value Experiment C Pen No. No. of tests Max. value mmol/l Min. value mmol/l Mean value mmol/l SD. mmol/l C.V. “/, Analysis of variances Ratio between/within P value
blood glucose estimations
1 10 4.0 3.2 3.46 0.25 7.36
with six different meters on three blood samples.
2 10 4.3 3.0 3.54 0.34 9.53
3 10 4.0 3.0 3.51 0.27 1.59
5 11 4.0 2.1 3.54 0.40 11.30
6 11 4.4 2.8 3.86 0.50 12.95
meters
All 63 4.4 2.1 3.60 0.37 10.28 1.57 > 0.05
1 8 12.1 10.1 10.80 0.71 6.51
2 8 11.8 10.1 10.75 0.58 5.40
3 8 11.0 10.1 10.50 0.28 2.11
4 7
11.4 10.4 11.00 0.31 2.82
5 7 11.6 10.3 10.90 0.40 3.61
6 7 11.3 10.1 10.81 0.41 3.19
meters
All 45 12.1 10.1 10.79 0.48 4.45 0.95 > 0.05
1 10 21.2 16.8 19.27 1.20 6.23
2 10 21.4 17.8 19.31 0.92 4.16
3 10 21.3 18.5 19.47 0.78 4.01
meters
deviation. C.V. = Coefficient of variation.
4 10 18.9 18.1 18.57 0.28 1.51
5 10 20.0 17.2 18.95 0.86 4.54
6 10 19.2 18.0 18.64 0.51 2.14
All 60 21.4 16.8 19.04 0.85 4.46 2.11 > 0.05
SD. = Standard
4 11 4.1 3.0 3.60 0.35 9.12
(3) Correlation of patients’ own testing with the ExacTech system and laboratory determinations of BGC. Eighteen patients took part in this investigation. Five did not complete the study, three for various personal reasons, two because they could not obtain sufficient amounts of blood for the reference samples. None dropped out because of difficulties in handling the ExacTech system. The ExacTech meters were used by the patients for 2 weeks, during which time they attempted to make three BGC profiles of seven measurements each. Control blood samples were collected in microvettesTM, and kept in the refrigerator until the next day when they were analysed in the laboratory. Statistical methods (1) The laboratory study. At each of the three BGCs (approximately 4, 10 and 20 mmol/l) the means, standard deviations and ranges of blood glucose concentrations were estimated by repeated measurements with six different ExacTech meters. An analysis of variances was performed to test whether the variance within the distributions of measurements assigned to the meters differed from variance between these distributions. Also, coefficients of variance (estimated standard deviation divided by estimated mean at each BGC, in percent) were calculated. (2) Comparison of 50pairs of observations of BGC made with the ExacTech system and a standard method. A coefficient of correlation was estimated using linear regression analysis. (3) Comparison of the patients’ own BGC measurements with ExacTech meters and a standard laboratory method. The measurements made by the patients with the ExacTech system were correlated by Spearman rank correlation tests to the results obtained in the laboratory on samples collected by the patients. Slopes and intercepts on the y-axis were calculated by a linear regression analysis.
Results Table 1 shows the results of the laboratory study. At each BGC, each of the six meters contributed with 7-11 measurements. The estimated coefficient of variation was highest for the lowest BGC. None of the variance ratios were statistically significant, indicating that no systematical variation attributable to the meters per se was observed. In Fig. 2 are shown the results of the linear regression analysis done on 50 pairs of measurements performed with the ExacTech system and the standard laboratory method. The coefficient of correlation was 0.95 (P < 0.001, df = 48), the slope 0.96, and the intercept on the y-axis 1.14 mmol/l. Thirteen patients completed HMBG with the ExacTech system and collected sufficient amounts of blood for later laboratory measurements of blood glucose. The results are seen in Table 2. The r values ranged from 0.03 to 0.98, in seven it was 0.90 or above. In two the Yvalue was not significantly different from zero. Slopes and intercepts on the y-axis were calculated for the remaining 11 patients by a parametric regression analysis. In all but one case the slope was less
ul 8
& 15 D 0
.;.,,,,;.: ...+
z
fl 10. t”
s
w
.; . ,,,’
’
I
;‘.; . . ,;: ..f . .’
,..‘.
. ,,,I... _ /.,. 5. :,.:’ I’ ,I ..,I ,.,’ ,,,’ ,/ ,,I’ ,.: ,,”
Fig. 2. Comparison of 50 pairs of glucose determinations by the ExacTech system and a standard laboratory method (Cobas Mira). r = 0.95 (P < 0.001).
89 TABLE 2 Correlation Patient No.
1 2 3 4 5 6 7 8 9 10 11 12 13
analysis of BGC determined
by the patients
by the ExacTech system and by a standard
laboratory
method
No. of measurements
r value
P value
Slope
Intercept
17 14 16 21 16 17 17 20 19 14 20 19 16
0.524 0.941 0.946 0.729 0.796 0.573 0.936 0.983 0.980 0.897 0.927 0.038 0.252
0.03 < 0.000 1 < 0.0001 0.0002 0.0002 0.0145 < 0.000 1 < 0.000 1 < 0.000 1 < 0.000 1 < 0.000 1 > 0.05 > 0.05
0.2748 0.7575 0.8539 0.6347 0.8140 0.5557 0.8732 0.8828 0.8741 1.0411 0.9128
6.5940 3.3619 1.5792 2.0972 2.4015 2.4716 2.2234 0.3370 0.4047 2.2131 2.1641
The r values are calculated
by Spearman
tests, the slopes and intercepts
than unity, and in all the intercept on the y-axis was positive, indicating a higher reading at low blood glucose levels with the ExacTech system than with the standard dehydrogenase method. Fourteen patients completed the questionary on their opinion on the ExacTech system. They all felt that it was just as good or better than their usual meter. They all stated that it was less complicated to operate. Six patients found the display somewhat difficult to read.
Discussion The ExacTech system, a new device for home monitoring of blood glucose, differs both in design and technique from hitherto known systems. The system was assessed in a number of ways in order to estimate the reliability under laboratory conditions and to compare readings with measurements done with a standard dehydrogenase method, with special reference to operation of the instrument by patients under conditions of daily life. In the laboratory the performance of the ExacTech system was found acceptable, as ex-
on the y-axis by linear regression
analysis.
pressed by low coefficients of variation, except perhaps for low values where it was approximately 10%. From the analysis of variances we may conclude, that the reliability of the ExacTech system is independent on the individual meter used. In the out-patient part of the study, readings with the ExacTech meters were done by two of the authors and compared to measurements made in the laboratory. A coefficient of correlation of 0.95 was found on 50 pairs of observation. The intercept on the y-axis was 1.14 and the slope 0.96, indicating that the ExacTech meter may give higher readings at low blood glucose values than the ordinary laboratory method used by us. The part of the study concerned with home measurements of blood glucose confirmed these observations. The slope was less than unity in all but one experiment, and the intercept on the y-axis positive in all. There was a number of methodological and technical problems involved in this part of the protocol. Firstly, very well regulated patients have a narrow range of blood glucose concentrations leading to a low coefficient of correlation and giving information only on a small interval of possible blood glucose
90
concentrations. Secondly, collecting blood samples in small plastic vessels for laboratory determinations is not very easy, and should probably be practiced more by the patients, if such experiments are to be repeated. The overall performance of the ExacTech system was in accordance with the results found with reflectance meters [4,5,11,12], and since the patients judged that the meter was easy to operate, we feel that the ExacTech system can be recommended for daily use by patients interested in HMBG. It should be noted, that higher results may be obtained by the ExacTech system at very low blood glucose concentrations. Among the advantages of the ExacTech system are the very simple operation, the omission of wiping of the reagent strips, and absence of the risk of contaminating the meter with blood. The reaction time is short (30 s), and the patients do not need to care about the timing, except for pressing the on/off switch immediately upon insertion of the strip into the meter. Further, the meter is very small and handy. A new model with a larger digital display has recently been marketed.
Acknowledgements The authors wish to thank Aase Odfeldt, Reamed, Denmark, for providing the meters and strips used in the study, and Anders Green, M.D. for help with the statistical analyses.
References 1 Sonksen, P.H., Judd, S. and Lowy, C. (1980) Home monitoring of blood glucose. New approach to management of insulin dependent diabetic patients in Great Britain. Diabet. Care 3, 100-107. 2 Mazze, RX, Pasmantier, R., Murphy, J.A. and Shamon, H. (1985) Self-monitoring of capillary blood glucose. Changing the performance of individuals with diabetes. Diabet. Care 8, 207-213. 3 Consensus statement on self-monitoring ofblood glucose. (1987) Diabet. Care 10, 95-99. 4 Reeves, M.L., Forhan, S.E., Skyler, J.S. and Peterson, C.M. (1981) Comparison of methods for blood glucose monitoring. Diabet. Care 4, 404-406. 5 Schersten, B., Ktihl, C., Hollender, A. and Ekman, R. (1974) Blood glucose measurement with dextrostix and a new reflectance meter. Br. Med. J. 3, 384-387. 6 Updike, S.J., Schults, M.C., Capelli, C.C. et al. (1988) Laboratory evaluation of a new reusable blood glucose sensor. Diabet. Care 11, 801-807. L., Peterson, C.M., Dudley, J.D., I Jovanovic-Peterson, Kilo, C. and Ellis B. (1988) Identifying sources of error in self-monitoring of blood glucose. Diabet. Care 11, 791-794. the Molecular 8 Lehninger, A.L. (1975) Biochemistry: Basis of Cell Structure and Function. 2nd Edn., pp. 258-259, Worth Publishers, New York. 9 Matthews, D.R., Holman, R.R., Bown E. et al. (1987) Pen-sized digital 30-second blood glucose meter. Lancet i, 778-779. 10 Wiles, P.G. and Watkins, P.J. (1983) Capillary blood collecting system for glucose determination. Postgrad. Med. J. 59,288-290. K.M. and 11 North, D.S., Steiner, SF., Woodhouse, Maddy, J.A. (1987) Home monitors of blood glucose: comparison of precision and accuracy. Diabet. Care 10, 360-366. L.A., Carter, 12 Clarke, W.L., Cox, D., Gonder-Frederick, W. and Pohl, S.L. (1987) Evaluating clinical accuracy of systems for self-monitoring of blood glucose. Diabet. Care 10, 622-628.
10 (1990) 85-90
85
Elsevier DIABET 00421
The ExacTech blood glucose testing system Kirsten Ohm Kyvik, .Jette Traulsen, Departments
Birgitte Reinholdt
of Medicine and Clinical Chemistry, Fredericia
and Anders Fwland
Hospital, Denmark
(Received 17 October 1989) (Revision received 29 March 1990) (Accepted 30 March 1990)
Summary The ExacTech system, a new device for home measurement of blood glucose was tested in the laboratory, in the out-patient clinic, and by diabetic patients. The system is based on an electrochemical principle, and consists of specially impregnated strips and a small, pencil-shaped meter. (1) Six meters were tested in the laboratory at blood glucose concentrations of 4, 10 and 20 mmol/l. Low coefficients of variation were found at 10 and 20 mmol/l, but those at 4 mmol/l were rather high (approximately 10%). Analysis of variances showed no difference in the between and the within variation of the meters. (2) The blood glucose concentrations of 50 consecutive out-patients were determined by the ExacTech system and a standard laboratory method. Correlation analysis showed an I value of 0.95 (P < 0.001). (3) The results obtained by 13 patients repeating the correlation experiment were in agreement with the second part of the study. The ExacTech system is very simple to operate by the patients, and can be recommended for home monitoring of blood glucose. Key words: Diabetes mellitus; Home monitoring
of blood glucose; Glucose meter
Introduction Home monitoring of blood glucose (HMBG) is recommended as a means to improve metabolic control in diabetes mellitus [ l-31. The most commonly used systems are based on reagent strips impregnated with glucose oxidase and a dye. The procedure includes timing, wiping and rinsing of the strip [ 1,4,5]. Less complicated systems have now been developed [ 6,7]. One new system is the Address for correspondence: Anders Freland, M.D., Department of Medicine, Fredericia Hospital, DK 7000 Fredericia, Denmark. 0168-8227/90/$03.50
0 1990 Elsevier Science Publishers
ExacTech blood glucose testing system based on an electrochemical reaction. We wanted to test the system both when used by skilled personnel and by patients. The protocol included three separate studies: (1) A laboratory investigation with repeated measurements at different blood glucose concentrations on a number of instruments operated by experienced laboratory technicians. (2) Comparison by correlation analysis of measurements on blood samples tested by the ExacTech system and a standard laboratory glucose dehydrogenase method. (3) Comparison by correlation analyses of
B.V. (Biomedical
Division)
measurements done by the patients at HMBG with the ExacTech system, and samples collected by the patients and later analysed in the laboratory. Finally, the patients were asked to answer a questionary on their opinion on the ExacTech system.
Materials and Methods The ExacTech system The ExacTech meter (Fig. 1) is 136 mm long, has a diameter of 15 mm, and the form of a pen. At one end there is an on/off switch, at the other a slit for the insertion of a reagent strip. On the side there is a digital display showing the BGC in mmol/l or mg/dl. The reagent area of the strips is impregnated with glucose oxidase, which catalyzes the conversion of the glucose of the blood specimen into glucuronic acid [ 81. The electrons generated by this process are transferred by a ferrocene mediator to the underlying electrodes [ 91. The current is proportional to the BGC of the test specimen. The result is shown on the display after 30 s. The meter is calibrated with a special test strip for each new batch of reagent strips. Two control solutions of low and high BGC are also available, permitting the patients to perform a quality control. At BGCs higher than 16 mmol/l (280 mg/dl), the display shows a request for checking the urine for ketone bodies. The patients Fifty patients with insulin-treated diabetes mellitus took part in the second section of the study.
They all attended the out-patient clinic of the Fredericia Hospital, Denmark. The participants were between 18 and 79 years old. No special inclusion or exclusion criteria were applied. Eighteen patients, aged 17-61 years, took part in section 3 of the study. They were all familiar with HMBG and with collecting blood samples in microvettesTM (for HbA,, determinations). Patients with known anaemia, polycythaemia, high values of s-urate, s-cholesterol, and s-triglycerides were excluded, as were patients with known abuse of salicylates. All patients accepted to participate on the basis of written and verbal information. The study was approved by the local ethical committee. Reference blood samples For part 2 of the study, samples of whole capillary blood for reference glucose estimations were collected in test tubes containing heparin and a haemolysing agent. The glucose content of the haemolysate is stable during 1 week at room temperature. For part 3 the blood was collected in small plastic vessels (microvettesTM, Sarstedt, F.R.G.). The microvettes contain sodium fluoride and heparin. The glucose concentration has been reported to be stable for 28 days [ lo]. Blood glucose was determined in the laboratory by a standard glucose dehydrogenase method (Cobas MiraTM, Merck). Study design (1) The laboratory study. Three samples of heparinized venous blood with BGCs of approximately 4, 10 and 20 mmol/l (72, 180 and 360 mg/dl) were measured with six ExacTech
CllP /
Fig. 1. The ExacTech blood glucose meter and reagent strips.
On/Off Button /
87
instruments. All reagent strips were from the same batch. Twenty-five ,ul of blood were used for each test. The button switch was activated immediately after application of the blood. Approximately 10 determinations were done at each BGC level on each meter, depending on the amount of blood available. (2) Comparison of BGCs measured by the ExacTech system and a standard method. Fifty
patients attending the out-patient clinic for their usual control were asked to participate. A drop of capillary blood from an ear lobe or a finger tip was used for measuring the BGC by the ExacTech system. A further 20 ~1 of blood from the same prick was collected in a test tube for analysis on the same day in the laboratory. Two of the authors did all the blood sampling and BGC measurements with the ExacTech system.
TABLE 1 Results of repeated Experiment A Pen No. No. of tests Max. value mmol/l Min. value mmol/l Mean value mmol/l SD. mmol/l C.V. z Analysis of variances Ratio between/within P value Experiment B Pen No. No. of tests Max. value mmol/l Min. value mmol/l Mean value mmol/l S.D. mmol/l C.V. ;, Analysis of variances Ratio between/within P value Experiment C Pen No. No. of tests Max. value mmol/l Min. value mmol/l Mean value mmol/l SD. mmol/l C.V. “/, Analysis of variances Ratio between/within P value
blood glucose estimations
1 10 4.0 3.2 3.46 0.25 7.36
with six different meters on three blood samples.
2 10 4.3 3.0 3.54 0.34 9.53
3 10 4.0 3.0 3.51 0.27 1.59
5 11 4.0 2.1 3.54 0.40 11.30
6 11 4.4 2.8 3.86 0.50 12.95
meters
All 63 4.4 2.1 3.60 0.37 10.28 1.57 > 0.05
1 8 12.1 10.1 10.80 0.71 6.51
2 8 11.8 10.1 10.75 0.58 5.40
3 8 11.0 10.1 10.50 0.28 2.11
4 7
11.4 10.4 11.00 0.31 2.82
5 7 11.6 10.3 10.90 0.40 3.61
6 7 11.3 10.1 10.81 0.41 3.19
meters
All 45 12.1 10.1 10.79 0.48 4.45 0.95 > 0.05
1 10 21.2 16.8 19.27 1.20 6.23
2 10 21.4 17.8 19.31 0.92 4.16
3 10 21.3 18.5 19.47 0.78 4.01
meters
deviation. C.V. = Coefficient of variation.
4 10 18.9 18.1 18.57 0.28 1.51
5 10 20.0 17.2 18.95 0.86 4.54
6 10 19.2 18.0 18.64 0.51 2.14
All 60 21.4 16.8 19.04 0.85 4.46 2.11 > 0.05
SD. = Standard
4 11 4.1 3.0 3.60 0.35 9.12
(3) Correlation of patients’ own testing with the ExacTech system and laboratory determinations of BGC. Eighteen patients took part in this investigation. Five did not complete the study, three for various personal reasons, two because they could not obtain sufficient amounts of blood for the reference samples. None dropped out because of difficulties in handling the ExacTech system. The ExacTech meters were used by the patients for 2 weeks, during which time they attempted to make three BGC profiles of seven measurements each. Control blood samples were collected in microvettesTM, and kept in the refrigerator until the next day when they were analysed in the laboratory. Statistical methods (1) The laboratory study. At each of the three BGCs (approximately 4, 10 and 20 mmol/l) the means, standard deviations and ranges of blood glucose concentrations were estimated by repeated measurements with six different ExacTech meters. An analysis of variances was performed to test whether the variance within the distributions of measurements assigned to the meters differed from variance between these distributions. Also, coefficients of variance (estimated standard deviation divided by estimated mean at each BGC, in percent) were calculated. (2) Comparison of 50pairs of observations of BGC made with the ExacTech system and a standard method. A coefficient of correlation was estimated using linear regression analysis. (3) Comparison of the patients’ own BGC measurements with ExacTech meters and a standard laboratory method. The measurements made by the patients with the ExacTech system were correlated by Spearman rank correlation tests to the results obtained in the laboratory on samples collected by the patients. Slopes and intercepts on the y-axis were calculated by a linear regression analysis.
Results Table 1 shows the results of the laboratory study. At each BGC, each of the six meters contributed with 7-11 measurements. The estimated coefficient of variation was highest for the lowest BGC. None of the variance ratios were statistically significant, indicating that no systematical variation attributable to the meters per se was observed. In Fig. 2 are shown the results of the linear regression analysis done on 50 pairs of measurements performed with the ExacTech system and the standard laboratory method. The coefficient of correlation was 0.95 (P < 0.001, df = 48), the slope 0.96, and the intercept on the y-axis 1.14 mmol/l. Thirteen patients completed HMBG with the ExacTech system and collected sufficient amounts of blood for later laboratory measurements of blood glucose. The results are seen in Table 2. The r values ranged from 0.03 to 0.98, in seven it was 0.90 or above. In two the Yvalue was not significantly different from zero. Slopes and intercepts on the y-axis were calculated for the remaining 11 patients by a parametric regression analysis. In all but one case the slope was less
ul 8
& 15 D 0
.;.,,,,;.: ...+
z
fl 10. t”
s
w
.; . ,,,’
’
I
;‘.; . . ,;: ..f . .’
,..‘.
. ,,,I... _ /.,. 5. :,.:’ I’ ,I ..,I ,.,’ ,,,’ ,/ ,,I’ ,.: ,,”
Fig. 2. Comparison of 50 pairs of glucose determinations by the ExacTech system and a standard laboratory method (Cobas Mira). r = 0.95 (P < 0.001).
89 TABLE 2 Correlation Patient No.
1 2 3 4 5 6 7 8 9 10 11 12 13
analysis of BGC determined
by the patients
by the ExacTech system and by a standard
laboratory
method
No. of measurements
r value
P value
Slope
Intercept
17 14 16 21 16 17 17 20 19 14 20 19 16
0.524 0.941 0.946 0.729 0.796 0.573 0.936 0.983 0.980 0.897 0.927 0.038 0.252
0.03 < 0.000 1 < 0.0001 0.0002 0.0002 0.0145 < 0.000 1 < 0.000 1 < 0.000 1 < 0.000 1 < 0.000 1 > 0.05 > 0.05
0.2748 0.7575 0.8539 0.6347 0.8140 0.5557 0.8732 0.8828 0.8741 1.0411 0.9128
6.5940 3.3619 1.5792 2.0972 2.4015 2.4716 2.2234 0.3370 0.4047 2.2131 2.1641
The r values are calculated
by Spearman
tests, the slopes and intercepts
than unity, and in all the intercept on the y-axis was positive, indicating a higher reading at low blood glucose levels with the ExacTech system than with the standard dehydrogenase method. Fourteen patients completed the questionary on their opinion on the ExacTech system. They all felt that it was just as good or better than their usual meter. They all stated that it was less complicated to operate. Six patients found the display somewhat difficult to read.
Discussion The ExacTech system, a new device for home monitoring of blood glucose, differs both in design and technique from hitherto known systems. The system was assessed in a number of ways in order to estimate the reliability under laboratory conditions and to compare readings with measurements done with a standard dehydrogenase method, with special reference to operation of the instrument by patients under conditions of daily life. In the laboratory the performance of the ExacTech system was found acceptable, as ex-
on the y-axis by linear regression
analysis.
pressed by low coefficients of variation, except perhaps for low values where it was approximately 10%. From the analysis of variances we may conclude, that the reliability of the ExacTech system is independent on the individual meter used. In the out-patient part of the study, readings with the ExacTech meters were done by two of the authors and compared to measurements made in the laboratory. A coefficient of correlation of 0.95 was found on 50 pairs of observation. The intercept on the y-axis was 1.14 and the slope 0.96, indicating that the ExacTech meter may give higher readings at low blood glucose values than the ordinary laboratory method used by us. The part of the study concerned with home measurements of blood glucose confirmed these observations. The slope was less than unity in all but one experiment, and the intercept on the y-axis positive in all. There was a number of methodological and technical problems involved in this part of the protocol. Firstly, very well regulated patients have a narrow range of blood glucose concentrations leading to a low coefficient of correlation and giving information only on a small interval of possible blood glucose
90
concentrations. Secondly, collecting blood samples in small plastic vessels for laboratory determinations is not very easy, and should probably be practiced more by the patients, if such experiments are to be repeated. The overall performance of the ExacTech system was in accordance with the results found with reflectance meters [4,5,11,12], and since the patients judged that the meter was easy to operate, we feel that the ExacTech system can be recommended for daily use by patients interested in HMBG. It should be noted, that higher results may be obtained by the ExacTech system at very low blood glucose concentrations. Among the advantages of the ExacTech system are the very simple operation, the omission of wiping of the reagent strips, and absence of the risk of contaminating the meter with blood. The reaction time is short (30 s), and the patients do not need to care about the timing, except for pressing the on/off switch immediately upon insertion of the strip into the meter. Further, the meter is very small and handy. A new model with a larger digital display has recently been marketed.
Acknowledgements The authors wish to thank Aase Odfeldt, Reamed, Denmark, for providing the meters and strips used in the study, and Anders Green, M.D. for help with the statistical analyses.
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