A minimally invasive system for glucose area under the curve measurement using interstitial fluid extraction technology: evaluation of the accuracy and usefulness with oral glucose tolerance tests in subjects with and without diabetes.

BACKGROUND: Recent studies have highlighted the importance of managing postprandial hyperglycemia, but adequate monitoring of postprandial glucose remains difficult because of wide variations in levels. We have therefore developed a minimally invasive system to monitor postprandial glucose area under the curve (AUC). This system involves no blood sampling and uses interstitial fluid glucose (IG) AUC (IG-AUC) as a surrogate marker of postprandial glucose. This study aimed to evaluate the usefulness of this system by comparing data with the findings of oral glucose tolerance tests (OGTTs) in subjects with and without diabetes. SUBJECTS AND METHODS: The glucose AUC monitoring system was validated by OGTTs in 37 subjects with and 10 subjects without diabetes. A plastic microneedle array was stamped on the forearm to extract IG. A hydrogel patch was then placed on the pretreated area to accumulate IG. Glucose and sodium ion concentrations in the hydrogel were measured to calculate IG-AUC at 2-h postload glucose. Plasma glucose (PG) levels were measured every 30 min to calculate reference PG-AUC. RESULTS: IG-AUC correlated strongly with reference PG-AUC (r=0.93) over a wide range. The level of correlation between IG-AUC and maximum PG level was also high (r=0.86). The painless nature of the technique was confirmed by the response of patients to questionnaires. CONCLUSIONS: The glucose AUC monitoring system using IG provided good estimates of reference PG-AUC and maximum PG level during OGTTs in subjects with and without diabetes. This system provides easy-to-use monitoring of glucose AUC, which is a good indicator of postprandial glucose.

Measurement of glucose area under the curve using minimally invasive interstitial fluid extraction technology: evaluation of glucose monitoring concepts without blood sampling.

BACKGROUND: Monitoring postprandial hyperglycemia is crucial in treating diabetes, although its dynamics make accurate monitoring difficult. We developed a new technology for monitoring postprandial hyperglycemia using interstitial fluid (ISF) extraction technology without blood sampling. The glucose area under the curve (AUC) using this system was measured as accumulated ISF glucose (IG) with simultaneous calibration with sodium ions. The objective of this study was to evaluate this technological concept in healthy individuals. METHODS: Minimally invasive ISF extraction technology (MIET) comprises two steps: pretreatment with microneedles and ISF accumulation over a specific time by contact with a solvent. The correlation between glucose and sodium ion levels using MIET was evaluated in 12 subjects with stable blood glucose (BG) levels during fasting. BG and IG time courses were evaluated in three subjects to confirm their relationship while BG was fluctuating. Furthermore, the accuracy of glucose AUC measurements by MIET was evaluated several hours after a meal in 30 subjects. RESULTS: A high correlation was observed between glucose and sodium ion levels when BG levels were stable (R=0.87), indicating that sodium ion is a good internal standard for calibration. The variation in IG and BG with MIET was similar, indicating that IG is an adequate substitute for BG. Finally, we showed a strong correlation (R=0.92) between IG-AUC and BG-AUC after a meal. CONCLUSIONS: These findings validate the adequacy of glucose AUC measurements using MIET. Monitoring glucose using MIET without blood sampling may be beneficial to patients with diabetes.

The use of flow cytometry as a diagnostic test for malaria parasites.

A total of 453 clinical blood samples were determined for malaria parasites by flow cytometric assay (FCM) and reagents from Sysmex Corporation, Japan. In this study, the FCM greatly simplified and accelerated parasite detection, with sensitivity of 91.26%, specificity 86.28% and accuracy 87.42%. Overall, the parasite counts by flow cytometric measurement correlated well with the parasitemia measured by microscopic assay (regression coefficient = 0.9409). The detection limit was 0.05-0.1% parasitemia. No evidence of malaria parasites in either blood donor volunteers or other disease patients groups was determined by FCM. However, 48 samples who had been treated with antimalarial drugs and whose parasite microscopic counts were negative, showed false-positive results. When the data of these 48 samples were analyzed, they were found to have high levels of reticulocytes, ranging from 2.0-18.9%. This finding suggested that a high reticulocyte concentration in the blood may interfere with the performance of the FCM. Further improvement, by eliminating this interference, will make the FCM one of the most promising tests for malaria diagnosis.

Capillary blood flow during severe hemodilution observed by a noninvasive transcutaneous technique using flash epi-illumination.

Capillary red blood cell (RBC) flow in the skin of rat tail during an extreme hemodilution with albumin was microscopically observed with a completely noninvasive transcutaneous technique using flash epi-illumination. This illumination with a filter (center wavelength, 550 nm) caused RBC to become darker and contrast well with the background tissue since the light was absorbed by hemoglobin inside the RBC. The recorded videotape showed a clear image of RBC without tailing because of flash (strobe light) illumination, and this allowed accurate analysis of the RBC flow rate and capillary hematocrit. During hemodilution up to a 50% level of blood exchange, the functional capillary density remained unchanged and it started to decline significantly at the 60% level of blood exchange and reached 37 +/- 32% of the basal value at the 80% level of blood exchange. The RBC flow rates monotonously increased up to 294 +/- 110% of the basal value at the 60% level of blood exchange, which was in contrast to the abdominal aortic blood flow increase to 148 +/- 20%. Capillary hematocrit did not appear to fall in the same proportion as the systemic hematocrit, which coincided with the previous observations. These results indicate that microhemodynamic properties during hemodilution can be transcutaneously analyzed with this new technique without surgical preparation of the skin.