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Review
. 2020 Dec 9;6(2):e10201.
doi: 10.1002/btm2.10201. eCollection 2021 May.

A review of biomarkers in the context of type 1 diabetes: Biological sensing for enhanced glucose control

Kelilah L Wolkowicz  1   2 , Eleonora M Aiello  1   2 , Eva Vargas  3 , Hazhir Teymourian  3 , Farshad Tehrani  3 , Joseph Wang  3 , Jordan E Pinsker  2 , Francis J Doyle 3rd  1   2 , Mary-Elizabeth Patti  4 , Lori M Laffel  4 , Eyal Dassau  1   2   4
Affiliations
Review

A review of biomarkers in the context of type 1 diabetes: Biological sensing for enhanced glucose control

Kelilah L Wolkowicz et al. Bioeng Transl Med. .

Abstract

As wearable healthcare monitoring systems advance, there is immense potential for biological sensing to enhance the management of type 1 diabetes (T1D). The aim of this work is to describe the ongoing development of biomarker analytes in the context of T1D. Technological advances in transdermal biosensing offer remarkable opportunities to move from research laboratories to clinical point-of-care applications. In this review, a range of analytes, including glucose, insulin, glucagon, cortisol, lactate, epinephrine, and alcohol, as well as ketones such as beta-hydroxybutyrate, will be evaluated to determine the current status and research direction of those analytes specifically relevant to T1D management, using both in-vitro and on-body detection. Understanding state-of-the-art developments in biosensing technologies will aid in bridging the gap from bench-to-clinic T1D analyte measurement advancement.

Keywords: automated insulin delivery; biosensors; measurement; medical devices; nanobiology; type 1 diabetes.

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Conflict of interest statement

Dr. Dassau reports receiving grants from JDRF, NIH, and Helmsley Charitable Trust, personal fees from Roche and Eli Lilly, patents on artificial pancreas technology, and product support from Dexcom, Insulet, Tandem, and Roche. Dr. Dassau is currently an employee and shareholder of Eli Lilly and Company. The work presented in this manuscript was performed as part of his academic appointment and is independent of his employment with Eli Lilly and Company. Dr. Doyle reports equity, licensed IP and is a member of the Scientific Advisory Board of Mode AGC. Dr. Laffel reports grant support to her institution from NIH, JDRF, Helmsley Charitable Trust, Eli Lilly and Company, Insulet, Dexcom, and Boehringer Ingelheim; she receives consulting fees unrelated to the current report from Johnson & Johnson, Sanofi, NovoNordisk, Roche, Dexcom, Insulet, Boehringer Ingelheim, ConvaTec, Medtronic, Lifescan, Laxmi, and Insulogic. Dr. Patti reports receiving grant support, provided to her institution, from NIH, Helmsely Charitable Trust, Chan Zuckerberg Foundation, and Dexcom, patents related to hypoglycemia and pump therapy for hypoglycemia, and advisory board fees from Fractyl (unrelated to the current report). Dr. Pinsker reports grant support, provided to his institution, consulting fees, and speaker fees from Tandem Diabetes Care, grant support, provided to his institution, and advisory board fees from Medtronic, grant support, provided to his institution, and consulting fees from Eli Lilly, grant support and supplies, provided to his institution, from Insulet, and supplies, provided to his institution, from Dexcom.

Figures

FIGURE 1
FIGURE 1
Primary aspects of glucose regulation in normal physiology. White cubes represent glucose molecules, blue connectors represent insulin pathways, and green connectors represent glucagon pathways. Yellow connectors distinguish counter‐regulatory hormones, such as cortisol, epinephrine, and norepinephrine. Figure redrawn from Holt, Textbook of Diabetes, 2010
FIGURE 2
FIGURE 2
Representative examples of different in‐vitro and on‐body sensing approaches to measure diabetes‐related biomarkers. (a) Self‐monitoring blood glucose (SMBG) meter. Reprinted by permission from Reference 112. (b) Schematic illustration of the working principle of enzyme‐linked immunosorbent assay (ELISA) method for analyzing protein biomarkers. (c) Dual‐analyte glucose‐insulin (G/I) detection chip. Copyright (2019) Wiley. Used with permission from Reference 70, John Wiley and Sons. (d) Free CGM, Dexcom G6. Reproduced by permission from Dexcom, 75 Copyright (2020). (e) Microneedle‐based glucose monitoring system by Biolinq. Reprinted by permission from Biolinq, 84 Copyright (2020). (f) Microneedle‐based CKM coupled with CGM. Reprinted from American Chemical Society, 85 Copyright (2020). (g) Tattoo‐based noninvasive glucose monitoring. Reprinted by permission from American Chemical Society, 91 Copyright (2020). Further permissions related to the material excerpted should be directed to the ACS. (h) Fully‐integrated wristband sensor consisting of glucose, lactate, sodium, potassium, and temperature sensors. Reprinted by permission from Springer Nature: Nature, 98 Copyright (2016). (i) Epidermal tattoo‐based patch for simultaneous measurement of interstitial fluid (ISF) glucose and sweat alcohol. Reprinted from John Wiley and Sons, 99 Copyright (2018). (j) NovioSense tear glucose sensor. Reprinted by permission from References 105, 113. Further permissions related to the material excerpted should be directed to the ACS. (k) Cortisol sensor patch based on laser‐engraved graphene electrodes for analyzing cortisol in sweat. Reprinted from Reference 106, Copyright (2020), with permission from Elsevier. (l) Molecularly imprinted polymer (MIP) recognition‐based cortisol patch for analyzing cortisol in sweat. Reprinted from Reference 107. Copyright The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY‐NC). http://creativecommons.org/licenses/by‐nc/4.0/
See this image and copyright information in PMC

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