Mass spectral determination of fasting tear glucose concentrations in nondiabetic volunteers.

BACKGROUND There is considerable disagreement regarding the concentration of glucose in tears and its relationship to the concentration in blood. Improved sampling and analysis methods may resolve these discrepancies and possibly provide a basis for in situ tear glucose sensors. METHODS We used liquid chromatography (LC) with electrospray ionization mass spectrometry (ESI-MS) to determine glucose in 1-muL tear fluid samples obtained from 25 fasting study participants. Tear fluid was collected with microcapillaries and a slitlamp microscope. RESULTS The median (range) of fasting tear glucose concentrations was 28 (7-161) micromol/L or 0.50 (0.13-2.90) mg/dL. The SD of tear glucose measurements for individuals varied linearly with the mean tear glucose concentration and was approximately half of the mean. We found no significant difference in tear glucose concentrations between contact lens users and nonusers (P = 0.715). We observed significant correlations between fasting blood and tear glucose concentrations (R = 0.50, P = 0.01). CONCLUSIONS Our tear fluid collection and analysis method enables reliable measurement of equilibrium, fasting tear glucose concentrations. These concentrations are lower than those previously reported for nondiabetic persons. Larger population studies are required to determine correlations between blood and tear glucose concentrations and to determine the utility of contact lens-based sensors for the monitoring of diabetes. Our methods are applicable for study of other tear fluid analytes and may prove useful for monitoring other disease states.

[1]  P. Jackson,et al.  Genetic comparison of Bacillus anthracis and its close relatives using amplified fragment length polymorphism and polymerase chain reaction analysis , 1999, Journal of applied microbiology.

[2]  R. Heim,et al.  Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel , 2001, Genetics in medicine : official journal of the American College of Medical Genetics.

[3]  Joanne Slavin,et al.  Whole grains and human health , 2004, Nutrition Research Reviews.

[4]  J. SantaLucia,et al.  The thermodynamics of DNA structural motifs. , 2004, Annual review of biophysics and biomolecular structure.

[5]  David D. Clark,et al.  Direct visualization of cystic fibrosis transmembrane regulator mutations in the clinical laboratory setting. , 2004, Clinical chemistry.

[6]  Milan Macek,et al.  Cystic fibrosis: A worldwide analysis of CFTR mutations—correlation with incidence data and application to screening , 2002, Human mutation.

[7]  G. Smith,et al.  Metabolism of apigenin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. , 1972, The Biochemical journal.

[8]  G. Castaldo,et al.  Molecular Diagnosis of Cystic Fibrosis: Comparison of Four Analytical Procedures , 2003, Clinical chemistry and laboratory medicine.

[9]  M. Mock,et al.  Diversity among French Bacillus anthracis Isolates , 2002, Journal of Clinical Microbiology.

[10]  A. Carattoli,et al.  Anthrax in animals and a farmer in Alto Adige, Italy. , 2006, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[11]  M. Weiner,et al.  Flow cytometric platform for high-throughput single nucleotide polymorphism analysis. , 2001, BioTechniques.

[12]  Angelika Domschke,et al.  Initial clinical testing of a holographic non-invasive contact lens glucose sensor. , 2006, Diabetes technology & therapeutics.

[13]  M. Rugge,et al.  Origin of spurious multiple bands in the amplification of microsatellite sequences. , 1999, Molecular pathology : MP.

[14]  B. Danielsson,et al.  Application of supercritical carbon dioxide for the extraction of alkylresorcinols from rye bran , 2005 .

[15]  H. Adlercreutz,et al.  Human plasma kinetics and relative bioavailability of alkylresorcinols after intake of rye bran. , 2006, The Journal of nutrition.

[16]  T. Fotsis.  The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS--II. Fractionation and quantitation of the main groups of estrogen conjugates. , 1987, Journal of steroid biochemistry.

[17]  M. Hugh-jones,et al.  Characterization of the variable-number tandem repeats in vrrA from different Bacillus anthracis isolates , 1997, Applied and environmental microbiology.

[18]  L. Braverman,et al.  Tear glucose detection of hyperglycemia. , 1968, American journal of ophthalmology.

[19]  D. Makris,et al.  Comparison of quercetin and a non-orthohydroxy flavonol as antioxidants by competing in vitro oxidation reactions. , 2001, Journal of agricultural and food chemistry.

[20]  C. Seal.  Whole grains and CVD risk , 2006, Proceedings of the Nutrition Society.

[21]  Angelika Domschke,et al.  Clinical Trial of a Non-invasive Ocular Glucose Sensor , 2001 .

[22]  E. Lyon,et al.  Distinguishing different DNA heterozygotes by high-resolution melting. , 2005, Clinical chemistry.

[23]  P R Chatterjee,et al.  Estimation of tear glucose level and its role as a prompt indicator of blood sugar level. , 2003, Journal of the Indian Medical Association.

[24]  Tanja Popovic,et al.  Molecular Subtyping of Bacillus anthracis and the 2001 Bioterrorism-Associated Anthrax Outbreak, United States , 2002, Emerging infectious diseases.

[25]  D. Daffonchio,et al.  Diversity of Bacillus anthracis Strains in Georgia and of Vaccine Strains from the Former Soviet Union , 2006, Applied and Environmental Microbiology.

[26]  H. Adlercreutz,et al.  Whole-grain rye bread consumption by women correlates with plasma alkylresorcinols and increases their concentration compared with low-fiber wheat bread. , 2005, The Journal of nutrition.

[27]  L. Griffiths,et al.  Metabolism of myricetin and related compounds in the rat. Metabolite formation in vivo and by the intestinal microflora in vitro. , 1972, The Biochemical journal.

[28]  T. Trotta,et al.  Detection of anthrax vaccine virulence factors by polymerase chain reaction. , 2001, Vaccine.

[29]  P. Åman,et al.  Dietary alkylresorcinols: absorption, bioactivities, and possible use as biomarkers of whole-grain wheat- and rye-rich foods. , 2004, Nutrition reviews.

[30]  C. Lapierre,et al.  Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. , 2003, The American journal of clinical nutrition.

[31]  L. Price,et al.  Multiple-Locus Variable-Number Tandem Repeat Analysis Reveals Genetic Relationships within Bacillus anthracis , 2000, Journal of bacteriology.

[32]  C. Nusbaum,et al.  Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. , 1998, Science.

[33]  W. Mandecki,et al.  Microtransponders, the miniature RFID electronic chips, as platforms for cell growth in cytotoxicity assays , 2006, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[34]  Paul Keim,et al.  Anthrax molecular epidemiology and forensics: using the appropriate marker for different evolutionary scales. , 2004, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[35]  N. Gerry,et al.  Universal DNA microarray method for multiplex detection of low abundance point mutations. , 1999, Journal of molecular biology.

[36]  Joseph R Lakowicz,et al.  A glucose-sensing contact lens: from bench top to patient. , 2005, Current opinion in biotechnology.

[37]  S. Asher,et al.  Photonic crystal glucose-sensing material for noninvasive monitoring of glucose in tear fluid. , 2004, Clinical chemistry.

[38]  J. Haddow,et al.  Clinical sensitivity of prenatal screening for cystic fibrosis via CFTR carrier testing in a United States panethnic population , 2004, Genetics in Medicine.

[39]  D K Sen,et al.  Tear glucose levels in normal people and in diabetic patients. , 1980, The British journal of ophthalmology.

[40]  N. J. van Haeringen,et al.  Collection method dependant concentrations of some metabolites in human tear fluid, with special reference to glucose in hyperglycaemic conditions , 1977, Albrecht von Graefes Archiv für klinische und experimentelle Ophthalmologie.

[41]  I. Kubo,et al.  Molluscicides from the cashew Anacardium occidentale and their large-scale isolation , 1986 .

[42]  M. Weiner,et al.  Fluorescent microsphere‐based readout technology for multiplexed human single nucleotide polymorphism analysis and bacterial identification , 2001, Human mutation.

[43]  Anna-Maria Linko-Parvinen,et al.  Cereal alkylresorcinols as dietary biomarkers - absorption and occurrence in biological membranes , 2006 .

[44]  R. Sack,et al.  Tear Glucose Dynamics in Diabetes Mellitus , 2006, Current eye research.

[45]  R M Hill,et al.  Human tear glucose. , 1982, Investigative ophthalmology & visual science.

[46]  H. Adlercreutz,et al.  Kinetics of the appearance of cereal alkylresorcinols in pig plasma , 2006, British Journal of Nutrition.

[47]  P. Keim,et al.  Molecular Diversity of Bacillus anthracis in Italy , 2005, Journal of Clinical Microbiology.

[48]  Weimin Sun,et al.  Technical validation of a TM Biosciences Luminex-based multiplex assay for detecting the American College of Medical Genetics recommended cystic fibrosis mutation panel. , 2006, The Journal of molecular diagnostics : JMD.

[49]  Carl T Wittwer,et al.  High-resolution genotyping by amplicon melting analysis using LCGreen. , 2003, Clinical chemistry.

[50]  L. Colón,et al.  Evaluation of lacrimal fluid as an alternative for monitoring glucose in critically ill patients , 2005, Intensive Care Medicine.

[51]  J. Haddow,et al.  Updated assessment of cystic fibrosis mutation frequencies in non-Hispanic Caucasians , 2002, Genetics in Medicine.

[52]  Peter Herbrechtsmeier,et al.  Clinical trial of a noninvasive contact lens glucose sensor. , 2004, Diabetes technology & therapeutics.

[53]  Gilles Vergnaud,et al.  Genotyping of Bacillus anthracis strains based on automated capillary 25-loci Multiple Locus Variable-Number Tandem Repeats Analysis , 2006, BMC Microbiology.

[54]  L A Colón,et al.  Analysis of tear fluid by CE/LIF: a noninvasive approach for glucose monitoring. , 1996, Journal of capillary electrophoresis.

[55]  P. Åman,et al.  Identification of cereal alkylresorcinol metabolites in human urine-potential biomarkers of wholegrain wheat and rye intake. , 2004, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[56]  S. Salzberg,et al.  The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria , 2003, Nature.

[57]  A. Rakin,et al.  Intriguing diversity of Bacillus anthracis in eastern Poland--the molecular echoes of the past outbreaks. , 2004, FEMS microbiology letters.

[58]  Justin T. Baca,et al.  Analysis of tear glucose concentration with electrospray ionization mass spectrometry , 2007, Journal of the American Society for Mass Spectrometry.

[59]  C. N. Gundry,et al.  Amplicon melting analysis with labeled primers: a closed-tube method for differentiating homozygotes and heterozygotes. , 2003, Clinical chemistry.

[60]  R. Margraf,et al.  Mutation scanning of the RET protooncogene using high-resolution melting analysis. , 2006, Clinical chemistry.

[61]  Joseph R. Lakowicz,et al.  A Glucose Sensing Contact Lens: A Non-Invasive Technique for Continuous Physiological Glucose Monitoring , 2003, Journal of Fluorescence.

[62]  L A Colón,et al.  Determination of Glucose in Submicroliter Samples by CE-LIF Using Precolumn or On-Column Enzymatic Reactions. , 1997, Analytical chemistry.

[63]  Carl T Wittwer,et al.  Sensitivity and specificity of single-nucleotide polymorphism scanning by high-resolution melting analysis. , 2004, Clinical chemistry.

[64]  L. Price,et al.  Bacillus anthracis Diversity in Kruger National Park , 2000, Journal of Clinical Microbiology.

[65]  J. Cheadle,et al.  Population variation of common cystic fibrosis mutations , 1994 .

[66]  H. Adlercreutz,et al.  Gas chromatographic-mass spectrometric method for the determination of alkylresorcinols in human plasma. , 2002, Analytical biochemistry.

[67]  R. Müller,et al.  Possibility of Bacterial Recruitment of Plant Genes Associated with the Biosynthesis of Secondary Metabolites1 , 2003, Plant Physiology.