Glucose lowering strategies with insulin

M Joan Taylor, Krishan P Chauhan, Tarsem S Sahota

Abstract


People with type 1 diabetes must use insulin and a large fraction of those with type 2 condition also do so. Many therefore struggle with the unpredictable balancing of insulin dose with calorie intake and utility. A healthy pancreas makes meticulous adjustment on a continuous basis that present therapeutic insulin administration cannot match. However, much progress has been made to make it simpler to inject both background and fast-acting boost insulins with a view to better mimicking normal pancreatic output. The present fast insulins are reviewed with accent on the primary amino acid structures of the biosynthetic types that diffuse more quickly than regular insulin that associates in hexamers. This makes boost doses kinetically and clinically more effective, allowing people to inject better estimated boost and corrective doses. Formulation advances are discussed for their present and potential contributions. The newer slow-acting insulins are also described and compared, their advantage also being kinetic with a lower likelihood of inducing overnight hypoglycaemia when used optimally. Finally, the appreciation of the advantages of alternative routes of administration such as oral and peritoneal are included in this review because of the possibility of altering the hepatic to peripheral ratio, the reasons for which are more effective but less obesogenic insulin activity. The logistics of oral insulin are summarised in terms of the risks to the insulin structure, the facilitation of paracellular uptake at the apical surface and the paradoxically advantageous hepatic first pass. Other non-invasive routes are also included in the review.

Keywords


new insulins, insulin amino acid modifications, conjugations, formulatory changes, unfolding and aggregation protection, closed loop, delivery routes, hepatic to peripheral ratio

Full Text:

PDF HTML

References


Campbell MS, Schatz DA, Chen V, and T1D Exchange Clinic Network. A contrast between children and adolescents with excellent and poor control: the T1D Exchange Clinic Registry experience. Pediatr Diabetes 2014;15(2):110–17. https://doi.org/10.1111/pedi.12067

Christie D, Thompson R, Sawtell, M, et al. Effectiveness of a structured educational intervention using psychological delivery methods in children and adolescents with poorly controlled type 1 diabetes: a cluster- randomized controlled trial of the CASCADE intervention. BMJ Open Diabetes Res Care 2016;4(1):e000165. https://doi.org/10.1136/bmjdrc-2015-000165

Pinhas-Hamiel O, Hamiel U, Boyko V, Graph-Barel C, Reichman B, Lerner-Geva L. Trajectories of HbA1c levels in children and youth with type 1 diabetes. PloS One 2014;9(10):e109109. https://doi.org/10.1371/journal.pone.0109109

McCall AL, Farhy LS. Treating type 1 diabetes: from strategies for insulin delivery to dual hormonal control. Minerva Endocrinol 2013;38(2):145–63.

Bailey CJ. Glucose-lowering therapies in type 2 diabetes: opportunities and challenges for peptides. Peptides 2018;100:9–17. https://doi.org/10.1016/j.peptides.2017.11.012

Jayakrishnapillai P, Nair SV, Kamalasanan K. Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes. Colloids and Surfaces B: Biointerfaces 2017;53:123–31. https://doi.org/10.1016/j.colsurfb.2017.02.017

Reno CM, Litvin M, Clark AL, Fisher SJ. Defective counterregulation and hypoglycemia unawareness in diabetes: mechanisms and emerging treatments. Endocrinol Metab Clin North Am 2013;42(1):15–38. https://doi.org/10.1016/j.ecl.2012.11.005

Weiss MA. Design of ultra-stable insulin analogues for the developing world. J Health Spec 2013;1(2):59–70. https://doi.org/10.4103/1658-600X.114683

Woo VC. New insulins and new aspects in insulin delivery. Can J Diabetes 2015;39(4):335–43. https://doi.org/10.1016/j.jcjd.2015.04.006

Weiss MA, Lawrence MC. A thing of beauty: structure and function of insulin's "aromatic triplet". Diabetes Obes Metab 2018;20(Suppl 2):51–63. https://doi.org/10.1111/dom.13402

Gast K, Schüler A, Wolff M, et al. Rapid-acting and human insulins: hexamer dissociation kinetics upon dilution of the pharmaceutical formulation. Pharmaceut Res 2017;34(11):2270–86. https://doi.org/10.1007/s11095-017-2233-0

Mitchell DE, Fayter AER, Deller RC, Hasan M, Gutierrez-Marcos J, Gibson MI. Ice-recrystallization inhibiting polymers protect proteins against freeze-stress and enable glycerol-free cryostorage. Materials Horizons 2019;6(2):364–8. https://doi.org/10.1039/C8MH00727F

Mathieu C, Bode BW, Franek E, et al. Efficacy and safety of fast-acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): a 52-week, randomized, treat-to-target, phase III trial. Diabetes Obes Metab 2018;20(5):1148–55. https://doi.org/10.1111/dom.13205

Heise T, Zijlstra E, Nosek L, Rikte T, Haahr H. Pharmacological properties of faster-acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: a randomized, double-blind, crossover trial. Diabetes Obes Metab 2017;19(2): 208–15. https://doi.org/10.1111/dom.12803

Kildegaard J, Buckley ST, Nielsen RH, et al. Elucidating the mechanism of absorption of fast-acting insulin aspart: the role of niacinamide. Pharm Res 2019;36(3):49. https://doi.org/10.1007/s11095-019-2578-7

Walter HM, Timmler R, Mehnert H. Stabilized human insulin prevents catheter occlusion during continuous subcutaneous insulin infusion. Diabetes Res (Edinburgh, Scotland) 1990;13(2):75–7.

Lee HJ, McAuley A, Schilke KF, McGuire J. Molecular origins of surfactant-mediated stabilization of protein drugs. Adv Drug Deliv Rev 2011; 63(13):1160–71. https://doi.org/10.1016/j.addr.2011.06.015

Leelarathna L, Ashley D, Fidler C, Parekh W. The value of fast-acting insulin aspart compared with insulin aspart for patients with diabetes mellitus treated with bolus insulin from a UK health care system perspective. Ther Adv Endocrinol Metab 2018;9(7):187–97. https://doi.org/10.1177/2042018818766816

Tambascia MA, Eliaschewitz FG. Degludec: the new ultra-long insulin analogue. Diabetol Metab Syndr 2015;7:57. https://doi.org/10.1186/s13098-015-0037-0

Ma Z, Christiansen JS, Laursen T, Lauritzen T, Frystyk J. Short-term effects of NPH insulin, insulin detemir, and insulin glargine on the GH-IGF1-IGFBP axis in patients with type 1 diabetes. Eur J Endocrinol 2014; 171(4):471–9. https://doi.org/10.1530/EJE-14-0258

Madsbad S. LY2605541: a preferential hepato-specific insulin analogue. Diabetes 2014;63(2):390–2. https://doi.org/10.2337/db13-1646

Hirose T. Development of new basal insulin peglispro (LY2605541) ends in a disappointing result. Diabetol Int 2016;7(1):16–17. https://doi.org/10.1007/s13340-016-0255-1

Munoz-Garach A, Molina-Vega M, Tinahones FJ. How can a good idea fail? Basal insulin Peglispro [LY2605541] for the treatment of type 2 diabetes. Diabetes Ther 2017;8(1):9–22. https://doi.org/10.1007/s13300-016-0214-7

Battelino T, Omladič JŠ, Phillip M. Closed loop insulin delivery in diabetes. Best Pract Res Clin Endocrinol Metab 2015;29(3):315–25. https://doi.org/10.1016/j.beem.2015.03.001

Uduku C, Oliver N. Pharmacological aspects of closed loop insulin delivery for type 1 diabetes. Curr Opin Pharmacol 2017;36:29–33. https://doi.org/10.1016/j.coph.2017.07.006

Satin LS, Butler PC, Ha J, Sherman AS. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes. Mol Aspects Med 2015; 42:61–77. https://doi.org/10.1016/j.mam.2015.01.003

Priya G, Kalra S. A review of insulin resistance in type 1 diabetes: is there a place for adjunctive metformin? Diabetes Ther 2018;9(1):349–61. https://doi.org/10.1007/s13300-017-0333-9

Taylor MJ, Gregory R, Tomlins P, Jacob D, Hubble J, Sahota TS. Closed-loop glycaemic control using an implantable artificial pancreas in diabetic domestic pig (Sus scrofa domesticus). Int J Pharm 2016;500(1–2):371–8. https://doi.org/10.1016/j.ijpharm.2015.12.024

Dassau E, Renard E, Place J, et al. Intraperitoneal insulin delivery provides superior glycaemic regulation to subcutaneous insulin delivery in model predictive control-based fully-automated artificial pancreas in patients with type 1 diabetes: a pilot study. Diabetes Obes Metab 2017; 19(12):1698–705. https://doi.org/10.1111/dom.12999

Huyett LM, Dassau E, Zisser HC, Doyle FJ 3rd. Design and evaluation of a robust PID controller for a fully implantable artificial pancreas. Ind Eng Chem Res 2015;54(42):10311–21. https://doi.org/10.1021/acs.iecr.5b01237

Renard E. New modes of insulin delivery and new modes of monitoring of type 1 diabetes mellitus. Rev Prat 2018;68(6):620–7.

Zisser H. Clinical hurdles and possible solutions in the implementation of closed-loop control in type 1 diabetes mellitus. J Diabetes Sci Technol 2011;5(5):1283–6. https://doi.org/10.1177/193229681100500537

Rhea EM, Salameh TS, Banks WA. Routes for the delivery of insulin to the central nervous system: a comparative review. Exp Neurol 2019; 313:10–15. https://doi.org/10.1016/j.expneurol.2018.11.007

Frid AH, Kreugel G, Grassi G, et al. New insulin delivery recommendations. Mayo Clinic Proc 2016;91(9):1231–55. https://doi.org/10.1016/j.mayocp.2016.06.010

Easa N, Alany RG, Carew M, Vangala A. A review of non-invasive insulin delivery systems for diabetes therapy in clinical trials over the past decade. Drug Discovery Today 2019;24(2):440–51. https://doi.org/10.1016/j.drudis.2018.11.010

Chaturvedi K, Ganguly K, Nadagouda MN, Aminabhavi TM. Polymeric hydrogels for oral insulin delivery. J Control Release 2013;165(2):129–38. https://doi.org/10.1016/j.jconrel.2012.11.005

Grigoras AG. Polymer-lipid hybrid systems used as carriers for insulin delivery. Nanomed Nanotechnol Biol Med 2017;13(8):2425–37. https://doi.org/10.1016/j.nano.2017.08.005

Fonte P, Araújo F, Silva C, et al. Polymer-based nanoparticles for oral insulin delivery: revisited approaches. Biotechnol Adv 2015;33(6, Part 3):1342–54. https://doi.org/10.1016/j.biotechadv.2015.02.010

Anderson JM, Van Itallie CM. Physiology and function of the tight junction. Cold Spring Harb Perspect Biol 2009;1(2):a002584. https://doi.org/10.1101/cshperspect.a002584

Mukhopadhyay P, Mishra R, Rana D, Kundu PP. Strategies for effective oral insulin delivery with modified chitosan nanoparticles: a review. Prog Polymer Sci 2012;37(11):1457–75. https://doi.org/10.1016/j.progpolymsci.2012.04.004

Karavasili C, Fatouros DG. Smart materials: in situ gel-forming systems for nasal delivery. Drug Discovery Today 2016;21(1):157–66. https://doi.org/10.1016/j.drudis.2015.10.016

Tscheik C, Blasig IE, Winkler L. Trends in drug delivery through tissue barriers containing tight junctions. Tissue Barriers 2013;1(2):e24565. https://doi.org/10.4161/tisb.24565

Yeh T, Hsu L, Tseng MT, et al. Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening. Biomaterials 2011;32(26):6164–73. https://doi.org/10.1016/j.biomaterials.2011.03.056

Benediktsdóttir BE, Gudjónsson T, Baldursson Ó, Másson M. N-alkylation of highly quaternized chitosan derivatives affects the paracellular permeation enhancement in bronchial epithelia in vitro. Eur J Pharm Biopharm 2014;86(1):55–63. https://doi.org/10.1016/j.ejpb.2013.04.002

Maher S, Brayden DJ, Casettari L, Illum L. Application of permeation enhancers in oral delivery of macromolecules: an update. Pharmaceutics 2019;11(1):41. https://doi.org/10.3390/pharmaceutics11010041

Taverner A, Dondi R, Almansour K, et al. Enhanced paracellular transport of insulin can be achieved via transient induction of myosin light chain phosphorylation. J Control Release 2015;210:189–97. https://doi.org/10.1016/j.jconrel.2015.05.270

Lin Y, Mi F, Lin P, et al. Strategies for improving diabetic therapy via alternative administration routes that involve stimuli-responsive insulin-delivering systems. Adv Drug Deliv Rev 2019;139:71–82. https://doi.org/10.1016/j.addr.2018.12.001

Iyire A, Alaayedi M, Mohammed AR. Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers. Sci Rep 2016;6:32498. https://doi.org/10.1038/srep32498

Lancina MG, Shankar RK, Yang H. Chitosan nanofibers for transbuccal insulin delivery. J Biomed Mater Res A 2017;105(5):1252–9. https://doi.org/10.1002/jbm.a.35984

Xu Y, Zhang X, Zhang Y, Ye J, Wang HL, Xia X, et al. Mechanisms of deformable nanovesicles based on insulin-phospholipid complex for enhancing buccal delivery of insulin. Int J Nanomedicine 2018;13:7319–31. https://doi.org/10.2147/IJN.S175425

Matteucci E, Giampietro O, Covolan V, Giustarini D, Fanti P, Rossi R. Insulin administration: present strategies and future directions for a noninvasive (possibly more physiological) delivery. Drug Des Devel Ther 2015;9:3109–18. https://doi.org/10.2147/DDDT.S79322

Vernon G. Do insulin injections make you fat? Br J Gen Pract 2018; 68(669):188. https://doi.org/10.3399/bjgp18X695537

Yassin M, Sadowska Z, Tritsaris K, et al. Rectal insulin instillation inhibits inflammation and tumor development in chemically induced colitis. J Crohn's Colitis 2018;12(12):1459–74. https://doi.org/10.1093/ecco-jcc/jjy112

Nakadate Y, Sato T, Sato H, Koeva V, Schricker T. Hypoglycaemia after accidental ocular insulin injection. Br J Anaesth 2017;118(4):640–1. https://doi.org/10.1093/bja/aex065

Nightscout Foundation. We are not waiting. Nightscout support CGM in the cloud. 2019. Available: http://www.nightscout.info/.




DOI: https://doi.org/10.15277/bjd.2019.228

Refbacks

  • There are currently no refbacks.


The Journal of the Association of British Clinical Diabetologists