Tear Glucose Dynamics in Diabetes Mellitus

Lane, Jennifer D.; Krumholz, David M.; Sack, Robert A.; Morris, Carol A.

doi:10.1080/02713680600976552

Cited by 140 publications

(108 citation statements)

References 25 publications

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“…Given that aqueous tear film contains approximately 7 µL of tear fluid and the average rate of tear fluid production is 1.2 µL/min at baseline 18 , collecting larger volumes of tear fluid can cause a significant amount of irritation and induce mechanical stress on the ocular surface. Studies have also shown that lower tear fluid volume collected generally results in lower median glucose concentrations and less eye irritation 12,19 . Elevated TG levels can be prolonged for up to 30 minutes, further skewing the correlation with BG 14 .…”

Section: Significance Of Tear Fluid Collection Methodsmentioning

confidence: 99%

Self-monitoring of tear glucose: the development of a tear based glucose sensor as an alternative to self-monitoring of blood glucose

et al. 2016

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Tear glucose sensing for diabetes management has long been sought as an alternative to more invasive self-monitoring of blood glucose (SMBG). However, tear glucose sensors were known to have limitations, including correlation issues with blood glucose due to low sample volume, low concentration of glucose in the tear fluid, and evaporation of the tear sample. An engineering design approach to solve these problems led to the development of an integrated device capable of collecting the tear sample from the ocular surface with little to no stress on the eye, with an extremely low limit of detection, broad dynamic range, and rapid detection and analysis of sample. Here we present the development of a prototypical self-monitoring of tear glucose (SMTG) sensor, summarizing bench studies on the enzymes and their specificity, the development of the fluid capture device and its manufacture and performance and results of system testing in an animal study where safety, lag time and tear glucose to blood glucose correlation were assessed.

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Section: Significance Of Tear Fluid Collection Methodsmentioning

confidence: 99%

Self-monitoring of tear glucose: the development of a tear based glucose sensor as an alternative to self-monitoring of blood glucose

et al. 2016

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“…Changes in tear production and composition have been associated with diabetes, including elevated glucose levels, 31 an increase in advanced glycation end product modified proteins, 32 and a reduction in reflex tearing. 33 In this study, we investigated the expression levels of IGFBP3 and IGF-1 in human tears of normal and diabetic patients in vivo and following in vitro culture of telomerase-immortalized human corneal epithelial cells in elevated glucose.…”

Section: Introductionmentioning

confidence: 99%

Elevated IGFBP3 Levels in Diabetic Tears: A Negative Regulator of IGF-1 Signaling in the Corneal Epithelium

Buckner

Zhu

et al. 2012

The Ocular Surface

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Purpose To determine the ratio of IGFBP3:IGF-1 in normal and diabetic human tears, and in telomerase-immortalized human corneal epithelial cells (hTCEpi) cultured under elevated glucose conditions and to correlate these changes with total and phosphorylated levels of IGF-1R. Methods Tear samples were collected noninvasively from diabetic subjects and non-diabetic controls; corneal sensitivity was assessed using a Cochet-Bonnet Aesthesiometer. Conditioned media were collected following culture of hTCEpi cells in normal (5 mM) and elevated (25 mM) glucose conditions; mannitol was used as an osmotic control. IGFBP3, IGF-1, and phosphorylated IGF-1R levels were assessed by ELISA. IGFBP3 and IGF-1R mRNA were assessed by real time polymerase chain reaction (PCR). Total and phosphorylated IGF-1R expression in whole cell lysates was assessed by western blot. Results There was a 2.8-fold increase in IGFBP3 in diabetic tears compared to non-diabetic controls (P=0.006); IGF-1 levels were not significantly altered. No difference in corneal sensitivity was detected between groups. The concentration of IGFBP3 in tears was independent of IGF-1. Consistent with human tear measurements in vivo, IGFBP3 secretion was increased 2.2 fold (P<0.001) following culture of hTCEpi cells under elevated glucose conditions in vitro. Treatment with glucose and the mannitol control reduced IGFBP3 mRNA (P<0.001). Total IGF-1R levels were unchanged. The increase in the IGFBP3:IGF-1 ratio detected in diabetic tears compared to normal controls blocked phosphorylation of the IGF-1R by IGF-1 (P<0.001) when tested in vitro. Conclusions Taken together, these in vivo and confirmatory in vitro findings suggest that the observed increase in IGFBP3 found in human tears may attenuate IGF-1R signaling in the diabetic cornea. A long-term increase in IGFBP3 may contribute to epithelial compromise and the pathogenesis of ocular surface complications reported in diabetes.

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“…33 Other studies indicate that diabetic and nondiabetic tear glucose mean values were 6.34 ± 0.7 mg/dl and 2.9 ± 0.5 mg/dl, respectively. 34 It should be noted that the discrepancy of the correlation coefficient (r) between blood glucose and tear glucose is caused by the different tear collection methods, e.g., filter paper or microcapillary. 35 Obviously, the development of an in situ ocular glucose sensor for diabetes control is heavily limited by the following factors: (1) it takes time to collect enough tear sample, i.e., at least 10 minutes is required to collect 10 µl of tear sample by using glass capillaries; 36 (2) the concentration of the glucose in tears is lower than that in blood; 37 and (3) very few suitable devices are able to compete against commercial blood glucose testers to quantitatively measure tear glucose in a short period of time.…”

Section: -28mentioning

confidence: 99%

Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose

Zhang

Hodge

Hutnick

et al. 2011

J Diabetes Sci Technol

136

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This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4-5 times a day to check blood glucose levels-almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently.

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Tear Glucose Dynamics in Diabetes Mellitus

Cited by 140 publications

References 25 publications

Self-monitoring of tear glucose: the development of a tear based glucose sensor as an alternative to self-monitoring of blood glucose

Self-monitoring of tear glucose: the development of a tear based glucose sensor as an alternative to self-monitoring of blood glucose

Elevated IGFBP3 Levels in Diabetic Tears: A Negative Regulator of IGF-1 Signaling in the Corneal Epithelium

Noninvasive Diagnostic Devices for Diabetes through Measuring Tear Glucose

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