Diabetes Metab J.  2017 Aug;41(4):265-274. 10.4093/dmj.2017.41.4.265.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients

• Uemura M
• Yano Y
• Suzuki T
• Yasuma T
• Sato T
• Morimoto A
• Hosoya S
• Suminaka C
• Nakajima H
• Gabazza EC
• Takei Y

• KMID: 2392467
• DOI: http://doi.org/10.4093/dmj.2017.41.4.265

Abstract

BACKGROUND
Continuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference.
METHODS
Thirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard.
RESULTS
A significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity.
CONCLUSION
We showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Keyword

Continuous glucose monitoring; Diabetes mellitus; Glucose area under the curve; Hyperglycemia; Nocturnal blood glucose; Post-prandial blood glucose

MeSH Terms

Area Under Curve
Blood Glucose
Diabetes Mellitus
Extracellular Fluid*
Glucose*
Humans
Hydrogel
Hyperglycemia
Inpatients
Mass Screening
Plastics
Sensitivity and Specificity
Sodium
Blood Glucose
Glucose
Hydrogel
Plastics
Sodium

Figure

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  Fig. 1 The process of minimally invasive interstitial fluid (ISF) extraction technology from pretreatment with a microneedle array to ISF glucose accumulation. Accumulated glucose corresponds to glucose area under the curve (AUC) during 8 hours.

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  Fig. 2 Correlation between glucose area under the curve (AUC) measured by continuous glucose monitoring (CGM) and interstitial fluid glucose AUC measured by minimally invasive interstitial fluid extraction technology (MIET) examined at (A) daytime (y=x, r=0.76) and (B) nighttime (y=x, r=0.82).

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  Fig. 3 The area under the receiver operating characteristics curves showed a positive discrimination threshold for interstitial fluid glucose of minimally invasive interstitial fluid extraction technology (MIET) area under the curve (AUC) of glucose level over 200 mg/dL by continuous glucose monitoring in all patients. The optimal cutoff value of MIET AUC to predict over 200 mg/dL of blood glucose level was 1,067.3 mg·hr/dL (sensitivity of 88.2% and specificity of 81.5%).

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  Fig. 4 No correlation between serum Na+ level and ratio of interstitial fluid glucose area under the curve (AUC) measured by minimally invasive interstitial fluid extraction technology (MIET) to glucose AUC measured by continuous glucose monitoring (CGM) in all patients.

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  Fig. 5 Response of the patients to a questionnaire about minimally invasive interstitial fluid extraction technology in all patients. (A) Pain at stamping. (B) Impression at stamped area.

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