Nischay K Rege1, Nelson F B Phillips, Michael A Weiss. 1. aDepartment of Biochemistry and Medical Scientist Training Program bDepartment of Biochemistry cDepartment of Biomedical Engineering dDepartment of Biochemistry eDepartment of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Abstract
PURPOSE OF REVIEW: The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. RECENT FINDINGS: Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. SUMMARY: Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.
PURPOSE OF REVIEW: The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsivepolymer encapsulation of insulin, and molecular modification of insulin itself. RECENT FINDINGS: Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. SUMMARY: Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.
Authors: Mary Courtney Moore; David E Kelley; Raul C Camacho; Peter Zafian; Tian Ye; Songnian Lin; Niels C Kaarsholm; Ravi Nargund; Terri M Kelly; Margaret Van Heek; Stephen F Previs; Christopher Moyes; Marta S Smith; Ben Farmer; Phil Williams; Alan D Cherrington Journal: Diabetes Date: 2018-03-14 Impact factor: 9.461
Authors: Mark A Jarosinski; Balamurugan Dhayalan; Nischay Rege; Deepak Chatterjee; Michael A Weiss Journal: Diabetologia Date: 2021-03-12 Impact factor: 10.122