Modeling Glucose Transport From Systemic Circulation to Sweat.

Sweat sensing may provide a noninvasive means of estimating blood biomarker levels if a number of technological hurdles can be overcome. This report describes progress on a physiologically based transport model relating sweat glucose and key electrolyte concentrations to those in blood. Iontophoretically stimulated sweat glucose and fasted blood glucose were simultaneously measured in 2 healthy human subjects. Sweat glucose was measured with a novel, prototype skin sweat collection/analysis system and blood glucose with a commercial fingerstick glucometer. These data, in combination with data from 3 published studies, were used to calibrate a dynamic mathematical model for glucose transport and uptake in human skin, followed by extraction into sweat. Model simulations revealed that experimental and literature sweat glucose values were well represented under varying physiologic conditions. The glucose model, calibrated under a variety of experimental conditions including electrical enhancement, revealed a 10 min blood-to-sweat lag time and a sweat/blood glucose level ranging from 0.001 to 0.02, depending on the sweat rate. These values are consistent with those reported in the literature. The developed model satisfactorily described the sweat-to-blood relationship for glucose concentrations measured under different conditions in 4 human studies including the present pilot study. The algorithm may be used to facilitate sweat biosensor development.

[1]  Jason Heikenfeld,et al.  Prolonged and localized sweat stimulation by iontophoretic delivery of the slowly-metabolized cholinergic agent carbachol. , 2018, Journal of dermatological science.

[2]  R. Frizzell,et al.  Physiology of epithelial chloride and fluid secretion. , 2012, Cold Spring Harbor perspectives in medicine.

[3]  K. Sato,et al.  The electrolyte composition of pharmacologically and thermally stimulated sweat: a comparative study. , 1970, The Journal of investigative dermatology.

[4]  S. K. Vashist Non-invasive glucose monitoring technology in diabetes management: a review. , 2012, Analytica chimica acta.

[5]  D. Klonoff Continuous glucose monitoring: roadmap for 21st century diabetes therapy. , 2005, Diabetes care.

[6]  Christopher J. Harvey,et al.  Formulation and stability of a novel artificial human sweat under conditions of storage and use. , 2010, Toxicology in vitro : an international journal published in association with BIBRA.

[7]  R. Latta,et al.  General method for the derivation and numerical solution of epithelial transport models , 2005, The Journal of Membrane Biology.

[8]  Yuri Dancik,et al.  Design and performance of a spreadsheet-based model for estimating bioavailability of chemicals from dermal exposure. , 2013, Advanced drug delivery reviews.

[9]  R O Potts,et al.  Electrical properties of skin at moderate voltages: contribution of appendageal macropores. , 1998, Biophysical journal.

[10]  V. Dua,et al.  Increased apical Na+ permeability in cystic fibrosis is supported by a quantitative model of epithelial ion transport , 2013, The Journal of physiology.

[11]  D. Accili,et al.  Glucose effects on skin keratinocytes: implications for diabetes skin complications. , 2001, Diabetes.

[12]  S. Cushman,et al.  The effects of insulin on the level and activity of the GLUT4 present in human adipose cells , 1995, Diabetologia.

[13]  R. Guy,et al.  Reverse Iontophoresis: Noninvasive Glucose Monitoring in Vivo in Humans , 1995, Pharmaceutical Research.

[14]  G. Kasting,et al.  Mathematical Models of Skin Permeability: Microscopic Transport Models and Their Predictions , 2014 .

[15]  Hye Rim Cho,et al.  A graphene-based electrochemical device with thermoresponsive microneedles for diabetes monitoring and therapy. , 2016, Nature nanotechnology.

[16]  R. Stern,et al.  The diagnosis of cystic fibrosis. , 1997, The New England journal of medicine.

[17]  Jason Heikenfeld,et al.  Enhancing glucose flux into sweat by increasing paracellular permeability of the sweat gland , 2018, PloS one.

[18]  K. Sato,et al.  A modified anaerobic method of sweat collection. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[19]  N P Smith,et al.  Development of models of active ion transport for whole-cell modelling: cardiac sodium-potassium pump as a case study. , 2004, Progress in biophysics and molecular biology.

[20]  J Heikenfeld,et al.  The microfluidics of the eccrine sweat gland, including biomarker partitioning, transport, and biosensing implications. , 2015, Biomicrofluidics.

[21]  R O Potts,et al.  Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes. , 2001, Biosensors & bioelectronics.

[22]  Jason Heikenfeld,et al.  Integrated sudomotor axon reflex sweat stimulation for continuous sweat analyte analysis with individuals at rest. , 2017, Lab on a chip.

[23]  F. Hariri,et al.  Interstitial fluid glucose dynamics during insulin-induced hypoglycaemia , 2005, Diabetologia.

[24]  Amay J Bandodkar,et al.  Non-invasive wearable electrochemical sensors: a review. , 2014, Trends in biotechnology.

[25]  D. Bovell The human eccrine sweat gland: Structure, function and disorders , 2015 .

[26]  E. Wilder,et al.  Human Subjects Testing of Sweat Stimulation Technologies , 2016 .

[27]  P J Stout,et al.  Comparison of glucose levels in dermal interstitial fluid and finger capillary blood. , 2001, Diabetes technology & therapeutics.

[28]  R. Potts,et al.  Physiological differences between interstitial glucose and blood glucose measured in human subjects. , 2003, Diabetes care.

[29]  Johannes M Nitsche,et al.  Dermal clearance model for epidermal bioavailability calculations. , 2012, Journal of pharmaceutical sciences.

[30]  N A W van Riel,et al.  Modeling glucose and water dynamics in human skin. , 2008, Diabetes technology & therapeutics.

[31]  L. Elsas,et al.  Increased glucose transport by human fibroblasts with a heritable defect in insulin binding. , 1989, Metabolism: clinical and experimental.

[32]  Dr. Morton H. Friedman Principles and Models of Biological Transport , 1986, Springer Berlin Heidelberg.

[33]  R. Potts,et al.  Correlation between sweat glucose and blood glucose in subjects with diabetes. , 2012, Diabetes technology & therapeutics.

[34]  J. Tamada,et al.  Effect of formulation factors on electroosmotic glucose transport through human skin in vivo. , 2005, Journal of pharmaceutical sciences.