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Portable urine glucose sensor
Portable urine glucose sensor
1
Narushi Ito1, Mariko Miyashita2 and Satoshi Ikeda2 1 PROVIGATE Inc., Tokyo, Japan, 2TANITA Corporation, Tokyo, Japan
1.1
Introduction
Development of a noninvasive blood glucose monitoring system is based on measurement of near infrared light passing through fingers and arms [1,2], measurement of interstitial fluid collected from the skin surface with a micro glucose sensor [3,4], and measurement of contact lens type tears [5,6], etc. It has been done over the past 30 years and enormous amount of research and development has been published, however, there are still no practical products. A series of products that have succeeded in development include a continuous blood glucose monitor and a flash glucose monitor that place small needles in the abdomen and the like. These are minimally invasive, and continuous monitoring for 2 weeks is possible. Meanwhile, as a noninvasive measurement, a portable urine glucose meter that makes it possible to quantitatively measure urine glucose levels correlated with blood glucose levels has been put to practical use. In this section, we describe the principle and structure of the microplanar type urine glucose sensor and examples of application of commercialized urine glucose meter to healthcare.
1.2
Significance of urine glucose measurement
In the urine glucose tests, diabetes screening tests are being conducted to test positive (1) or negative (2) by measuring fasting urine such as common in medical examinations. Positive (1) is based on 100 mg/dL as the urine glucose concentration. Medically urine glucose positivity is considered as a suspicious indicator of diabetes first. Then further inspections are necessary, because there are transient cases such as renal diabetes, stress, pregnancy, etc., in addition to other findings for diagnosis of diabetes. Ultimately diabetes is confirmed by the 75 g oral glucose tolerance test. Urine glucose test is regarded as an auxiliary test and a large number of screening tests are still being carried out at present, due to its advantage of noninvasive measurement. Chemical, Gas, and Biosensors for the Internet of Things and Related Applications. DOI: https://doi.org/10.1016/B978-0-12-815409-0.00001-2 © 2019 Elsevier Inc. All rights reserved.
4
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
Figure 1.1 Relationship between urine glucose concentration and blood glucose concentration after meal.
Changes in urine glucose concentration after meals are shown in Fig. 1.1. The postprandial urine glucose concentration is linked to blood glucose levels, and it is important that it does not overlook postprandial hyperglycemia occurring after meals. When the urine glucose concentration exceeds 50 mg/dL, it means that the blood glucose level exceeds the glucose excretion threshold of 160180 mg/dL in the kidney. Even when blood glucose level rises with the diet, it decreases after 1 hour due to the action of insulin. In other words, the blood glucose level measured at 2 hours after a meal usually returns to the normal range. On the other hand, it is known that the urine glucose concentration 2 hours after a meal reflects the elevated blood glucose level with the meal. As well, it is demonstrated that urine glucose level correlates with the mean blood glucose level.
1.3
Operating principle of urine glucose sensor and laminated structure
1.3.1 Principle of operation Urine glucose sensor is an enzyme electrode method combining glucose oxidase (GOX) and hydrogen peroxide electrode. The electrode is fabricated by photolithography technology. Glucose is enzymatically converted to hydrogen peroxide (H2O2) by GOX, and the yielded H2O2 is electrochemically detected by the electrodes. The enzymatic reaction (1) and the electrode reactions (2) are as follows: 1. Enzymatic reaction GOX: Glucose 1 O2!gluconolactone 1 H2O2 2. Electrochemical reactions at electrodes Working electrode: H2O2!2H1 1 O2 1 2e2
Portable urine glucose sensor
5
Figure 1.2 Perspective view of the sensor. Counter electrode: 2H1 11/2O2 1 2e2!H2O Entire electrode system: H2O2!H2O 1 1/2O2
A perspective view of the sensor is shown in Fig. 1.2. Three electrodes, a working electrode, a counter electrode, and a reference electrode, are formed in the hole of the cartridge. The working electrode and the counter electrode are Pt electrodes, and thin film Ag/AgCl electrodes are formed as reference electrode. The reference electrode has the role of stabilizing the potential after immersion in the solution. The outermost layer of the electrode is coated with a thin film of a fluorinated polymer to prevent contamination due to urine components while protecting the electrode system as a whole and stabilizing the operation of the electrodes for more than 1 year in solution.
1.3.2 Laminated structure of urine glucose sensor To accurately measure postprandial urine, means to eliminate the influence of vitamin C (ascorbic acid) among substances released from foods are required. Ascorbic acid has a reaction that gives electrons to an electrode and another reaction decomposing hydrogen peroxide, and it is typical of an interfering substance of an amperometric sensor. Furthermore, it is necessary to fabricate a membrane structure so that interfering substances other than ascorbic acid contained in the urine do not affect the measured values. Fig. 1.3 shows a laminated structure of the urine glucose sensor. This sensor is composed of four layers: a restricted permeable layer, an enzyme immobilized layer, a cation-exchanging layer, and an adhesive layer. 1. The restricted permeable layer has a wide measurement range from 10 to 2000 mg/dL, limiting the diffusion of molecules larger than glucose. It has the role of preventing the influence of adhered substances in urine. 2. The enzyme immobilized layer is the one where enzyme (GOX) and bovine serum albumin are crosslinked and immobilized so as not to inactivate the enzyme; as a result, repetition of the sensor is possible.
6
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
Figure 1.3 Laminated structure of the urine glucose sensor. 3. The cation-exchanging layer has the role of permeating hydrogen peroxide and limiting the diffusion of molecules larger than hydrogen peroxide. Furthermore, it has the function of preventing permeation of ionized molecules. 4. The adhesive layer has the role of covalently bonding the selectively permeable film, which is an organic material, to the surface of the glass substrate or the electrode and stably adhering for a long time in water.
This sensor is formed of a thin film of four layers with a total thickness of 1 µm or less, effectively eliminating the influence of interfering substances in the urine and an early time response [7].
1.4
Development of portable urine glucose meter
1.4.1 Composition of urine glucose meter This urine glucose meter consists of a body and a sensor. Portability is designed so that the sensor section is folded down to be compact, and at the time of measurement it is extended. Photo 1.1 shows a urine glucose meter in a stored state. Photo 1.2 shows the urine glucose meter extended at the time of measurement. The urine glucose meter sensor section is composed of a preservation solution bottle, which makes the sensor wet. The preservation solution is reserved to hold the sensor, which can cause optimal enzymatic reaction with pH buffer and physiological saline. After the sensor is taken out, it becomes possible to measure instantly. Photo 1.2 shows a urine glucose meter at the time of measurement. When measured, total length 210 mm of the meter can be directly applied to urine with one hand. The urine glucose sensor at the tip is equipped with a thermistor for detecting the water temperature so that the output can be corrected. The sensor needs to be
Portable urine glucose sensor
7
Photo 1.1 Urine glucose meter folded (closed).
Photo 1.2 Urine glucose meter extended (opened).
replaced either after 200 measurements or within 60 days due to the removable socket structure. The main body measures the minute current and controls the device. It also has a liquid crystal display that indicates urine glucose concentration, and switches for calibration and measurement value recall. It also operates for 8 months with one lithium battery.
1.4.2 Performance evaluation of urine glucose meter The final test of the urine glucose meter requires performance evaluation by the urine of patients. The results of simultaneous measurement of patients’ urine specimens with urine glucose meter and clinical urine glucose analyzer (A&T GA03R) and correlation evaluation are shown in Fig. 1.4. The primary equation obtained by the method of least squares is urine glucose meter ① Y 5 0.925 X 1 53.3, R 5 0.987, urine glucose meter ② Y 5 0.939 X 1 62.9, R 5 0.987, urine glucose meter ③ Y 5 0.968 X 1 40.4, R 5 0.99, showing a high correlation with the conventional clinical urine glucose analyzer. Especially, the deviation of the measured values in the low concentration region is small, although the deviation is medically regarded as a problem. However, Fig. 1.4 demonstrates sufficient results for performance of a compact and simple measuring instrument. As well, those results showed that as a self-measuring tool at home, its portability is a plus, and it can measure urine glucose with high accuracy with a small size of 210 mm in total length [8].
8
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
Figure 1.4 Correlation between urine glucose meter and clinical urine glucose analyzer.
1.5
Clinical application of urine glucose meter
1.5.1 Relationship between the amount of boiled rice and urine glucose concentration in impaired glucose tolerance Meal load test was conducted on subjects judged to have impaired glucose tolerance by 75 g oral glucose tolerance test. In the method, blood glucose level and urine glucose level up to 3 hours after starting a meal were measured for 320 kcal salad and meat, boiled rice with different amount of 100300 g (145435 kcal). The blood glucose level was measured using a self-monitoring blood glucose meter (GLUCOCARD: ARKRAY), and the urine glucose concentration was measured with a developed urine glucose meter. Fig. 1.5 (A) shows changes in blood glucose concentration, and (B) shows changes in urine glucose concentration. The results confirmed an increase in urine glucose concentration with the rise in blood glucose concentration reflecting the difference in the amount of boiled rice. In particular, differences in urine glucose concentrations of 400 and 600 mg/dL are difficult to determine with conventional urine glucose test paper. The above results indicate that the quantitative measurement using the urine glucose meter can accurately capture postprandial hyperglycemia that changes depending on the carbohydrate intake [9].
1.5.2 Results of urine glucose monitoring on impaired glucose tolerance case The results of urine glucose measurement before and after a meal for 7 days are shown in Fig. 1.6. In this impaired glucose tolerance case, self-monitoring of
Portable urine glucose sensor
9
Figure 1.5 Blood glucose concentration (BG) and urine glucose concentration (UG) differ by changing the volume of rice (In case of impaired glucose tolerance). (A) BG changes after meal; (B) UG changes after meal.
Figure 1.6 Results of urine glucose measurement before and after meal for 7 days (In case of impaired glucose tolerance).
urine glucose (SMUG) was carried out by instructing the user to pay attention to the relationship between urine glucose concentration after meals and meal contents. The meal content ingested was recorded at the same time. As a result, it was revealed that dietary control becomes possible by monitoring the urine glucose concentration after meals. Also, over the next 8 months, as a result of eating meals that did not raise the urine glucose concentration after meals, weight decreased from 63.9 to 59.0 kg, body fat decreased from 20.5% to 13.7%, and it was also effective to reduce body weight. In conclusion, postprandial hyperglycemia that occurs from early stage of diabetes can be controlled by urine glucose meter [9].
10
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
1.5.3 Results of a case of self-monitoring of urine glucose in diabetes SMUG was conducted for 6 months on a voluntary type 2 diabetes patient (woman aged 69 years, height 153.2 cm, weight 51.8 kg, BMI 22.1 kg/m2). The method was to measure urine glucose concentration 8 times a day (before morning, before breakfast, after breakfast, before lunch, after lunch, before dinner, after dinner, before going to bed). Also, meal contents were recorded at the same time. The doctor monitored the feedback of the relationship between the urine glucose concentration and meal contents after meals. Meanwhile, at a hospital every month, HbA1c and body weight were measured. The results of SMUG are shown in Fig. 1.7 The transition of measured values over 100 mg/dL during 4 months from the start of urine glucose measurement was 9 times in the first 2 weeks after SMUG began, 5 times in the next 2 weeks, 6 times in the next 2 weeks, then 3 times, 1 time, 0 times, 3 times, 0 times, and 3 times, all 2-week periods. HbA1c and body weight change are shown in Fig. 1.8. During the 5 months before SMUG, HbA1c had been in the 8% range, but it decreased from 8.7% (glycemic control status: unacceptable) to 5.8% (glycemic control status: excellent) in about 3 months after starting urine glucose measurement. Therefore, glycemic control improved. As a result, a decrease in HbA1c was observed 1 month after starting measurement of postprandial urine glucose concentration, and it was effective for blood glucose control of type 2 diabetic patients. The finding of the interview after use is that urine glucose measurement is easy to introduce and continue because it is noninvasive and the measured value changes dynamically in the range of 102000 mg/dL, so the results show it was easy to understand, and it was thought that the motivation for the patient’s blood glucose control was improved.
Figure 1.7 Results of SMUG during 4 months.
Portable urine glucose sensor
11
Figure 1.8 Results of HbA1c(JDS) and body weight change.
1.6
Conclusions
In conclusion, (1) urine glucose concentration at 2 hours after a meal is higher in proportion to the amount of ingested carbohydrate; and (2) SMUG is available for control of the meal contents, which suppresses postprandial hyperglycemia, indicating that HbA1c and body weight can be reduced. Recently, clinical trials comparing SMBG and SMUG levels of type 2 diabetes revealed that there is no difference in diet therapy effectiveness [10]. Postprandial hyperglycemia stimulates glucose spikes to vascular endothelial cells. As a result, it has been clarified that not only diabetes but also arteriosclerosis causing stroke and myocardial infarction can be incubated. As well, it is one of risk factors for dementia. Monitoring postprandial hyperglycemia with a urine glucose meter from the earliest stage of diabetes is recommended as a noninvasive healthcare tool that helps modify lifestyle of diet and exercise. Furthermore, a portable urine glucose meter integrating IoT and AI not only supports meals and exercise, but is thought to become an effective diabetes prevention tool customized to characteristics of individuals.
References [1] H.M. Heise, et al., Noninvasive blood glucose sensors based on near-infrared spectroscopy, Artif Organs 18 (1994) 439. [2] US Patent 5,553,616, Determination of concentrations of biological substances using raman spectroscopy and artificial neural network discriminator.
12
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
[3] US Patent 2005/0215872, Monitoring of physiological analytes. [4] N. Ito, et al., Development of a transcutaneous blood-constituent monitoring method using a suction effusion fluid collection technique and an ion-sensitive field-effect transistor glucose sensor, Med. Biol. Comput. 32 (1994) 242. [5] W.F. March, et al., Ocular glucose sensor, Trans. Am. Soc. Artif. Intern. Organs 28 (1982) 232. [6] WO2014/113174, Encapsulated electronics. [7] M. Miyashita, et al., Development of urine glucose meter based on micro-planer amperometric biosensor and its clinical application for self-monitoring of urine glucose, Biosensors Bioelectr. 24 (2009) 1336. [8] I. Yamaguchi, et al., Performance evaluation of urine glucose meter: repeatability, effects of interferential substances, and comparison with clinical glucose analyzer, Rinsyoukensa. 53 (2009) 237. [9] A. Ohashi, et al., Effect of food intake and its contents on postprandial urine glucose in diabetes candidates by digital urine glucose meter, Japan. Soc. Med. Biol. Eng. 42 (2004) 280. [10] J. Lu, et al., Comparable efficacy of self-monitoring of quantitative urine glucose with seif-monitoring of blood glucose on glycemic control in non-insulin-treated type 2 diabetes, Diab. Res. Clin. Pract. 93 (2011) 179.
1
Narushi Ito1, Mariko Miyashita2 and Satoshi Ikeda2 1 PROVIGATE Inc., Tokyo, Japan, 2TANITA Corporation, Tokyo, Japan
1.1
Introduction
Development of a noninvasive blood glucose monitoring system is based on measurement of near infrared light passing through fingers and arms [1,2], measurement of interstitial fluid collected from the skin surface with a micro glucose sensor [3,4], and measurement of contact lens type tears [5,6], etc. It has been done over the past 30 years and enormous amount of research and development has been published, however, there are still no practical products. A series of products that have succeeded in development include a continuous blood glucose monitor and a flash glucose monitor that place small needles in the abdomen and the like. These are minimally invasive, and continuous monitoring for 2 weeks is possible. Meanwhile, as a noninvasive measurement, a portable urine glucose meter that makes it possible to quantitatively measure urine glucose levels correlated with blood glucose levels has been put to practical use. In this section, we describe the principle and structure of the microplanar type urine glucose sensor and examples of application of commercialized urine glucose meter to healthcare.
1.2
Significance of urine glucose measurement
In the urine glucose tests, diabetes screening tests are being conducted to test positive (1) or negative (2) by measuring fasting urine such as common in medical examinations. Positive (1) is based on 100 mg/dL as the urine glucose concentration. Medically urine glucose positivity is considered as a suspicious indicator of diabetes first. Then further inspections are necessary, because there are transient cases such as renal diabetes, stress, pregnancy, etc., in addition to other findings for diagnosis of diabetes. Ultimately diabetes is confirmed by the 75 g oral glucose tolerance test. Urine glucose test is regarded as an auxiliary test and a large number of screening tests are still being carried out at present, due to its advantage of noninvasive measurement. Chemical, Gas, and Biosensors for the Internet of Things and Related Applications. DOI: https://doi.org/10.1016/B978-0-12-815409-0.00001-2 © 2019 Elsevier Inc. All rights reserved.
4
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
Figure 1.1 Relationship between urine glucose concentration and blood glucose concentration after meal.
Changes in urine glucose concentration after meals are shown in Fig. 1.1. The postprandial urine glucose concentration is linked to blood glucose levels, and it is important that it does not overlook postprandial hyperglycemia occurring after meals. When the urine glucose concentration exceeds 50 mg/dL, it means that the blood glucose level exceeds the glucose excretion threshold of 160180 mg/dL in the kidney. Even when blood glucose level rises with the diet, it decreases after 1 hour due to the action of insulin. In other words, the blood glucose level measured at 2 hours after a meal usually returns to the normal range. On the other hand, it is known that the urine glucose concentration 2 hours after a meal reflects the elevated blood glucose level with the meal. As well, it is demonstrated that urine glucose level correlates with the mean blood glucose level.
1.3
Operating principle of urine glucose sensor and laminated structure
1.3.1 Principle of operation Urine glucose sensor is an enzyme electrode method combining glucose oxidase (GOX) and hydrogen peroxide electrode. The electrode is fabricated by photolithography technology. Glucose is enzymatically converted to hydrogen peroxide (H2O2) by GOX, and the yielded H2O2 is electrochemically detected by the electrodes. The enzymatic reaction (1) and the electrode reactions (2) are as follows: 1. Enzymatic reaction GOX: Glucose 1 O2!gluconolactone 1 H2O2 2. Electrochemical reactions at electrodes Working electrode: H2O2!2H1 1 O2 1 2e2
Portable urine glucose sensor
5
Figure 1.2 Perspective view of the sensor. Counter electrode: 2H1 11/2O2 1 2e2!H2O Entire electrode system: H2O2!H2O 1 1/2O2
A perspective view of the sensor is shown in Fig. 1.2. Three electrodes, a working electrode, a counter electrode, and a reference electrode, are formed in the hole of the cartridge. The working electrode and the counter electrode are Pt electrodes, and thin film Ag/AgCl electrodes are formed as reference electrode. The reference electrode has the role of stabilizing the potential after immersion in the solution. The outermost layer of the electrode is coated with a thin film of a fluorinated polymer to prevent contamination due to urine components while protecting the electrode system as a whole and stabilizing the operation of the electrodes for more than 1 year in solution.
1.3.2 Laminated structure of urine glucose sensor To accurately measure postprandial urine, means to eliminate the influence of vitamin C (ascorbic acid) among substances released from foods are required. Ascorbic acid has a reaction that gives electrons to an electrode and another reaction decomposing hydrogen peroxide, and it is typical of an interfering substance of an amperometric sensor. Furthermore, it is necessary to fabricate a membrane structure so that interfering substances other than ascorbic acid contained in the urine do not affect the measured values. Fig. 1.3 shows a laminated structure of the urine glucose sensor. This sensor is composed of four layers: a restricted permeable layer, an enzyme immobilized layer, a cation-exchanging layer, and an adhesive layer. 1. The restricted permeable layer has a wide measurement range from 10 to 2000 mg/dL, limiting the diffusion of molecules larger than glucose. It has the role of preventing the influence of adhered substances in urine. 2. The enzyme immobilized layer is the one where enzyme (GOX) and bovine serum albumin are crosslinked and immobilized so as not to inactivate the enzyme; as a result, repetition of the sensor is possible.
6
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
Figure 1.3 Laminated structure of the urine glucose sensor. 3. The cation-exchanging layer has the role of permeating hydrogen peroxide and limiting the diffusion of molecules larger than hydrogen peroxide. Furthermore, it has the function of preventing permeation of ionized molecules. 4. The adhesive layer has the role of covalently bonding the selectively permeable film, which is an organic material, to the surface of the glass substrate or the electrode and stably adhering for a long time in water.
This sensor is formed of a thin film of four layers with a total thickness of 1 µm or less, effectively eliminating the influence of interfering substances in the urine and an early time response [7].
1.4
Development of portable urine glucose meter
1.4.1 Composition of urine glucose meter This urine glucose meter consists of a body and a sensor. Portability is designed so that the sensor section is folded down to be compact, and at the time of measurement it is extended. Photo 1.1 shows a urine glucose meter in a stored state. Photo 1.2 shows the urine glucose meter extended at the time of measurement. The urine glucose meter sensor section is composed of a preservation solution bottle, which makes the sensor wet. The preservation solution is reserved to hold the sensor, which can cause optimal enzymatic reaction with pH buffer and physiological saline. After the sensor is taken out, it becomes possible to measure instantly. Photo 1.2 shows a urine glucose meter at the time of measurement. When measured, total length 210 mm of the meter can be directly applied to urine with one hand. The urine glucose sensor at the tip is equipped with a thermistor for detecting the water temperature so that the output can be corrected. The sensor needs to be
Portable urine glucose sensor
7
Photo 1.1 Urine glucose meter folded (closed).
Photo 1.2 Urine glucose meter extended (opened).
replaced either after 200 measurements or within 60 days due to the removable socket structure. The main body measures the minute current and controls the device. It also has a liquid crystal display that indicates urine glucose concentration, and switches for calibration and measurement value recall. It also operates for 8 months with one lithium battery.
1.4.2 Performance evaluation of urine glucose meter The final test of the urine glucose meter requires performance evaluation by the urine of patients. The results of simultaneous measurement of patients’ urine specimens with urine glucose meter and clinical urine glucose analyzer (A&T GA03R) and correlation evaluation are shown in Fig. 1.4. The primary equation obtained by the method of least squares is urine glucose meter ① Y 5 0.925 X 1 53.3, R 5 0.987, urine glucose meter ② Y 5 0.939 X 1 62.9, R 5 0.987, urine glucose meter ③ Y 5 0.968 X 1 40.4, R 5 0.99, showing a high correlation with the conventional clinical urine glucose analyzer. Especially, the deviation of the measured values in the low concentration region is small, although the deviation is medically regarded as a problem. However, Fig. 1.4 demonstrates sufficient results for performance of a compact and simple measuring instrument. As well, those results showed that as a self-measuring tool at home, its portability is a plus, and it can measure urine glucose with high accuracy with a small size of 210 mm in total length [8].
8
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
Figure 1.4 Correlation between urine glucose meter and clinical urine glucose analyzer.
1.5
Clinical application of urine glucose meter
1.5.1 Relationship between the amount of boiled rice and urine glucose concentration in impaired glucose tolerance Meal load test was conducted on subjects judged to have impaired glucose tolerance by 75 g oral glucose tolerance test. In the method, blood glucose level and urine glucose level up to 3 hours after starting a meal were measured for 320 kcal salad and meat, boiled rice with different amount of 100300 g (145435 kcal). The blood glucose level was measured using a self-monitoring blood glucose meter (GLUCOCARD: ARKRAY), and the urine glucose concentration was measured with a developed urine glucose meter. Fig. 1.5 (A) shows changes in blood glucose concentration, and (B) shows changes in urine glucose concentration. The results confirmed an increase in urine glucose concentration with the rise in blood glucose concentration reflecting the difference in the amount of boiled rice. In particular, differences in urine glucose concentrations of 400 and 600 mg/dL are difficult to determine with conventional urine glucose test paper. The above results indicate that the quantitative measurement using the urine glucose meter can accurately capture postprandial hyperglycemia that changes depending on the carbohydrate intake [9].
1.5.2 Results of urine glucose monitoring on impaired glucose tolerance case The results of urine glucose measurement before and after a meal for 7 days are shown in Fig. 1.6. In this impaired glucose tolerance case, self-monitoring of
Portable urine glucose sensor
9
Figure 1.5 Blood glucose concentration (BG) and urine glucose concentration (UG) differ by changing the volume of rice (In case of impaired glucose tolerance). (A) BG changes after meal; (B) UG changes after meal.
Figure 1.6 Results of urine glucose measurement before and after meal for 7 days (In case of impaired glucose tolerance).
urine glucose (SMUG) was carried out by instructing the user to pay attention to the relationship between urine glucose concentration after meals and meal contents. The meal content ingested was recorded at the same time. As a result, it was revealed that dietary control becomes possible by monitoring the urine glucose concentration after meals. Also, over the next 8 months, as a result of eating meals that did not raise the urine glucose concentration after meals, weight decreased from 63.9 to 59.0 kg, body fat decreased from 20.5% to 13.7%, and it was also effective to reduce body weight. In conclusion, postprandial hyperglycemia that occurs from early stage of diabetes can be controlled by urine glucose meter [9].
10
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
1.5.3 Results of a case of self-monitoring of urine glucose in diabetes SMUG was conducted for 6 months on a voluntary type 2 diabetes patient (woman aged 69 years, height 153.2 cm, weight 51.8 kg, BMI 22.1 kg/m2). The method was to measure urine glucose concentration 8 times a day (before morning, before breakfast, after breakfast, before lunch, after lunch, before dinner, after dinner, before going to bed). Also, meal contents were recorded at the same time. The doctor monitored the feedback of the relationship between the urine glucose concentration and meal contents after meals. Meanwhile, at a hospital every month, HbA1c and body weight were measured. The results of SMUG are shown in Fig. 1.7 The transition of measured values over 100 mg/dL during 4 months from the start of urine glucose measurement was 9 times in the first 2 weeks after SMUG began, 5 times in the next 2 weeks, 6 times in the next 2 weeks, then 3 times, 1 time, 0 times, 3 times, 0 times, and 3 times, all 2-week periods. HbA1c and body weight change are shown in Fig. 1.8. During the 5 months before SMUG, HbA1c had been in the 8% range, but it decreased from 8.7% (glycemic control status: unacceptable) to 5.8% (glycemic control status: excellent) in about 3 months after starting urine glucose measurement. Therefore, glycemic control improved. As a result, a decrease in HbA1c was observed 1 month after starting measurement of postprandial urine glucose concentration, and it was effective for blood glucose control of type 2 diabetic patients. The finding of the interview after use is that urine glucose measurement is easy to introduce and continue because it is noninvasive and the measured value changes dynamically in the range of 102000 mg/dL, so the results show it was easy to understand, and it was thought that the motivation for the patient’s blood glucose control was improved.
Figure 1.7 Results of SMUG during 4 months.
Portable urine glucose sensor
11
Figure 1.8 Results of HbA1c(JDS) and body weight change.
1.6
Conclusions
In conclusion, (1) urine glucose concentration at 2 hours after a meal is higher in proportion to the amount of ingested carbohydrate; and (2) SMUG is available for control of the meal contents, which suppresses postprandial hyperglycemia, indicating that HbA1c and body weight can be reduced. Recently, clinical trials comparing SMBG and SMUG levels of type 2 diabetes revealed that there is no difference in diet therapy effectiveness [10]. Postprandial hyperglycemia stimulates glucose spikes to vascular endothelial cells. As a result, it has been clarified that not only diabetes but also arteriosclerosis causing stroke and myocardial infarction can be incubated. As well, it is one of risk factors for dementia. Monitoring postprandial hyperglycemia with a urine glucose meter from the earliest stage of diabetes is recommended as a noninvasive healthcare tool that helps modify lifestyle of diet and exercise. Furthermore, a portable urine glucose meter integrating IoT and AI not only supports meals and exercise, but is thought to become an effective diabetes prevention tool customized to characteristics of individuals.
References [1] H.M. Heise, et al., Noninvasive blood glucose sensors based on near-infrared spectroscopy, Artif Organs 18 (1994) 439. [2] US Patent 5,553,616, Determination of concentrations of biological substances using raman spectroscopy and artificial neural network discriminator.
12
Chemical, Gas, and Biosensors for the Internet of Things and Related Applications
[3] US Patent 2005/0215872, Monitoring of physiological analytes. [4] N. Ito, et al., Development of a transcutaneous blood-constituent monitoring method using a suction effusion fluid collection technique and an ion-sensitive field-effect transistor glucose sensor, Med. Biol. Comput. 32 (1994) 242. [5] W.F. March, et al., Ocular glucose sensor, Trans. Am. Soc. Artif. Intern. Organs 28 (1982) 232. [6] WO2014/113174, Encapsulated electronics. [7] M. Miyashita, et al., Development of urine glucose meter based on micro-planer amperometric biosensor and its clinical application for self-monitoring of urine glucose, Biosensors Bioelectr. 24 (2009) 1336. [8] I. Yamaguchi, et al., Performance evaluation of urine glucose meter: repeatability, effects of interferential substances, and comparison with clinical glucose analyzer, Rinsyoukensa. 53 (2009) 237. [9] A. Ohashi, et al., Effect of food intake and its contents on postprandial urine glucose in diabetes candidates by digital urine glucose meter, Japan. Soc. Med. Biol. Eng. 42 (2004) 280. [10] J. Lu, et al., Comparable efficacy of self-monitoring of quantitative urine glucose with seif-monitoring of blood glucose on glycemic control in non-insulin-treated type 2 diabetes, Diab. Res. Clin. Pract. 93 (2011) 179.