Article pubs.acs.org/ac
Evaluation of Commercial Glucometer Test Strips for Potential Measurement of Glucose in Tears Kyoung Ha Cha,† Gary C. Jensen,† Anant S. Balijepalli,† Bruce E. Cohan,‡ and Mark E. Meyerhoff*,† †
Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109-1055, United States EyeLab Group LLC, 2350 Washtenaw Avenue No. 4, Ann Arbor, Michigan, 48104-4525, United States
‡
ABSTRACT: Tear glucose measurements have been suggested as a potential alternative to blood glucose monitoring for diabetic patients. While previous work has reported that there is a correlation between blood and tear glucose levels in humans, this link has not been thoroughly established and additional clinical studies are needed. Herein, we evaluate the potential of using commercial blood glucose test strips to measure glucose in tears. Of several blood glucose strips evaluated, only one brand exhibits the low detection limit required for quantitating glucose in tears. Calibration of these strips in the range of 0−100 μM glucose with an applied potential of 150 mV to the working electrode yields a sensitivity of 0.127 nA/μM and a limit of quantitation (LOQ) of 9 μM. The strips also exhibit ≤13% error (n = 3) for 25, 50, and 75 μM glucose in the presence of 10 μM acetaminophen, 100 μM ascorbic acid, and 100 μM uric acid. Measurements of glucose in tears from nine normal (nondiabetic) fasting human subjects using strips yielded glucose values within the range of 5−148 μM (mean = 47 μM, median = 43 μM), similar to those for human tears reported by others with more complex LC−MS methods. The glucometer strip method could facilitate more clinical studies to determine whether tear glucose and blood glucose levels sufficiently correlate for application to routine measurements in tears to supplement blood glucose testing. This would be especially helpful for children, adolescents, other Type 1 diabetics, and also for Type 2 diabetics who require treatment with insulin and cannot tolerate multiple finger sticks per day.
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spectroscopy,7,8 optical coherence tomography, and measurement of tissue metabolic heat conformation;9 however, none are currently proven to be useful clinically.10 In addition, several in vivo sensing approaches have been proposed, including fluorescence spectroscopy,11,12 surface plasmon resonance of nanoparticles,13,14 electrical impedance measurements, and implantable/subcutaneous amperometric glucose sensors.15 Among these, only subcutaneous electrochemical glucose sensors are available commercially, although frequent calibration, short in vivo lifetimes, limited accuracy, and high cost have prevented their widespread use.15 Measurement of tear glucose concentrations is an emerging area of research and several studies have reported that there may be a clinically useful correlation between blood and tear glucose levels.16−19 Baca et al. recently reviewed studies of this correlation using different detection methods,20 concluding that there is evidence of a correlation; however, further studies are needed to determine the potential utility of tear glucose measurements to help achieve tight, yet safe, glycemic control. Methods for tear glucose measurement mandate a low micromolar range LOQ, high selectivity over potential interferences (e.g., ascorbic acid and uric acid), and measure-
he World Health Organization (WHO) reports that more than 347 million people worldwide live with diabetes. Over 1.1 million deaths in 2005 were caused by diabetes, and deaths attributed to diabetes are estimated to double by 2030.1 Regular measurement and control of blood glucose is essential to avoid life-threatening hyper- and hypoglycemic events and associated serious long-term complications.2 Normally, a personal blood glucometer with a test strip allows diabetics to monitor their blood glucose level by obtaining a small sample of capillary blood with a lancet, either from the fingertip or forearm. Optimal metabolic control is possible for these patients with a minimum of four checks per day.3 However, for children and adolescents with Type 1 diabetes on insulin therapy, this method of glucose monitoring is often recommended up to eight times a day.4 The resulting discomfort can limit patient compliance and lead to suboptimal blood glucose control4 as well as the risk of hypoglycemia. Although the recent availability of glucometer test strips with lower sample volume requirements (i.e.,
Evaluation of Commercial Glucometer Test Strips for Potential Measurement of Glucose in Tears Kyoung Ha Cha,† Gary C. Jensen,† Anant S. Balijepalli,† Bruce E. Cohan,‡ and Mark E. Meyerhoff*,† †
Department of Chemistry, University of Michigan, Ann Arbor, Michigan, 48109-1055, United States EyeLab Group LLC, 2350 Washtenaw Avenue No. 4, Ann Arbor, Michigan, 48104-4525, United States
‡
ABSTRACT: Tear glucose measurements have been suggested as a potential alternative to blood glucose monitoring for diabetic patients. While previous work has reported that there is a correlation between blood and tear glucose levels in humans, this link has not been thoroughly established and additional clinical studies are needed. Herein, we evaluate the potential of using commercial blood glucose test strips to measure glucose in tears. Of several blood glucose strips evaluated, only one brand exhibits the low detection limit required for quantitating glucose in tears. Calibration of these strips in the range of 0−100 μM glucose with an applied potential of 150 mV to the working electrode yields a sensitivity of 0.127 nA/μM and a limit of quantitation (LOQ) of 9 μM. The strips also exhibit ≤13% error (n = 3) for 25, 50, and 75 μM glucose in the presence of 10 μM acetaminophen, 100 μM ascorbic acid, and 100 μM uric acid. Measurements of glucose in tears from nine normal (nondiabetic) fasting human subjects using strips yielded glucose values within the range of 5−148 μM (mean = 47 μM, median = 43 μM), similar to those for human tears reported by others with more complex LC−MS methods. The glucometer strip method could facilitate more clinical studies to determine whether tear glucose and blood glucose levels sufficiently correlate for application to routine measurements in tears to supplement blood glucose testing. This would be especially helpful for children, adolescents, other Type 1 diabetics, and also for Type 2 diabetics who require treatment with insulin and cannot tolerate multiple finger sticks per day.
T
spectroscopy,7,8 optical coherence tomography, and measurement of tissue metabolic heat conformation;9 however, none are currently proven to be useful clinically.10 In addition, several in vivo sensing approaches have been proposed, including fluorescence spectroscopy,11,12 surface plasmon resonance of nanoparticles,13,14 electrical impedance measurements, and implantable/subcutaneous amperometric glucose sensors.15 Among these, only subcutaneous electrochemical glucose sensors are available commercially, although frequent calibration, short in vivo lifetimes, limited accuracy, and high cost have prevented their widespread use.15 Measurement of tear glucose concentrations is an emerging area of research and several studies have reported that there may be a clinically useful correlation between blood and tear glucose levels.16−19 Baca et al. recently reviewed studies of this correlation using different detection methods,20 concluding that there is evidence of a correlation; however, further studies are needed to determine the potential utility of tear glucose measurements to help achieve tight, yet safe, glycemic control. Methods for tear glucose measurement mandate a low micromolar range LOQ, high selectivity over potential interferences (e.g., ascorbic acid and uric acid), and measure-
he World Health Organization (WHO) reports that more than 347 million people worldwide live with diabetes. Over 1.1 million deaths in 2005 were caused by diabetes, and deaths attributed to diabetes are estimated to double by 2030.1 Regular measurement and control of blood glucose is essential to avoid life-threatening hyper- and hypoglycemic events and associated serious long-term complications.2 Normally, a personal blood glucometer with a test strip allows diabetics to monitor their blood glucose level by obtaining a small sample of capillary blood with a lancet, either from the fingertip or forearm. Optimal metabolic control is possible for these patients with a minimum of four checks per day.3 However, for children and adolescents with Type 1 diabetes on insulin therapy, this method of glucose monitoring is often recommended up to eight times a day.4 The resulting discomfort can limit patient compliance and lead to suboptimal blood glucose control4 as well as the risk of hypoglycemia. Although the recent availability of glucometer test strips with lower sample volume requirements (i.e.,
