International Journal of Diabetes and Endocrinology

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Sulfonylureas Induced Hypoglycemia in Diabetics - A Review

Received: Nov. 14, 2019    Accepted: Nov. 26, 2019    Published: Dec. 04, 2019
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Abstract

Diabetes is a metabolic disorder of glucose characterized by glucotoxicity, lipotoxicity and insulin resistance. In insulin resistance states, a higher level of insulin is needed to generate the usual body response to keep plasma glucose at physiologic level. The type 2 diabetics with insulin resistance cannot keep plasma glucose normal not because of absolute insulin deficiency but due to a relative deficiency as insulin is now required at a higher plasma level to achieve a near physiological or physiological plasma glucose level. Hence the need for a chemical agent to increase insulin secretion from the pancreatic beta cells at pharmacological dose (insulin secretagogues) was conceptualized and arrived at. Sulfonylureas are insulin secretagogues. Two generations of sulfonylurea’s are in use. The first and second. The class effects of sulfonylurea include weight gain, allergic reaction and hypoglycemia. But not enough emphasis is placed on the severity and grading of the hypoglycemia complicating use of sulfonylureas. Meanwhile hypoglycemia induced by sulfonylurea use is of various degree, severity and duration. The classification of hypoglycemia into grades in ADEMOLUS CLASSIFICATION OF HYPOGLYCEMIA makes it easier for scientist to understand, compare and monitor the severity of sulfonylureas. Mrs KFO is a 67 years old diabetic diagnosed over 8 years ago. She had asymptomatic hypoglycemia with a glucometer reading low (ADEMOLUS PHENOMENON) on a clinic day visit. She had been on glimepiride for three years. Mrs A. F. is a 75 years old diabetic diagnosed 4 years prior to presentation. She had a glucometer reading of low during a random blood sugar check at 8pm on day 2 of admission with associated general body weakness. She was on metformin and glibenclamide. Mrs. I E is a 72 years old diabetic who had a glucometer reading of low during her outpatient clinic visit. She was on gliclazide. Sulfonylureas use has been shown by these cases to be associated with symptomatic and asymptomatic very severe hypoglycemia. A possibility of synthesizing a new equally potent third generation of sulfonylureas with minimal or no hypoglycemic effect should be looked into.

DOI 10.11648/j.ijde.20190404.14
Published in International Journal of Diabetes and Endocrinology ( Volume 4, Issue 4, December 2019 )

This article belongs to the Special Issue Hypoglycemia in Diabetes

Page(s) 108-112
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Sulfonylureas, Hypoglycemia, Diabetes Mellitus

References
[1] Carey M, Kehlenbrink S. Hawkins M. Evidence for central regulation of glucose metabolism. J Biol Chem. 2013 Dec 6; 288 (49): 34981-8.
[2] Petersen MC, Vatner DF, Shulman GI. Regulation of hepatic glucose metabolism in health and disease. Nat Rev Endocrinol. 2017 Oct; 13 (10): 572-587.
[3] Stephen L. Aronoff, Kathy Berkowitz, Barb Shreiner, and Laura Want. Glucose Metabolism and Regulation: Beyond Insulin and Glucagon. Diabetes Spectrum 2004 Jul; 17 (3): 183-190.
[4] Bulcun E, Ekici M. Ekici A. Disorders of glucose metabolism and insulin resistance in patients with obstructive sleep apnoea syndrome. Int J Clin Pract. 2012 Jan; 66 (1): 91-7.
[5] Dubé MP. Disorders of glucose metabolism in patients infected with human immunodeficiency virus. Clin Infect Dis. 2000 Dec; 31 (6): 1467-75. Epub 2000 Nov 29.
[6] Chou JY, Jun HS, Mansfield BC. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase/glucose-6-phosphate transporter complexes. J Inherit Metab Dis. 2015 May; 38 (3): 511-9.
[7] Kaiser N, Leibowitz G, Nesher R. Glucotoxicity and beta-cell failure in type 2 diabetes mellitus. J Pediatr Endocrinol Metab. 2003 Jan; 16 (1): 5-22.
[8] Shinji Kawahito, Hiroshi Kitahata, and Shuzo Oshita. Problems associated with glucose toxicity: Role of hyperglycemia-induced oxidative stress. World J Gastroenterol. 2009 Sep 7; 15 (33): 4137–4142.
[9] Del Prato S.. Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies. Diabet Med. 2009 Dec; 26 (12): 1185- 92.
[10] Gisela Wilcox. Insulin and Insulin Resistance. Clin Biochem Rev. 2005 May; 26 (2): 19–39.
[11] Andrew M. Freeman; Kristina Soman-Faulkner; Nicholas Pennings. Insulin Resistance. May 10, 2019.
[12] Daniele Sola, Luca Rossi, Gian Piero Carnevale Schianca, Pamela Maffioli, Marcello Bigliocca, Roberto Mella, Francesca Corlianò, Gian Paolo Fra, Ettore Bartoli, and Giuseppe Derosa. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015 Aug 12; 11 (4): 840–848.
[13] Ryan A. Costello; Abhijit Shivkumar. Sulfonylureas. Last Update: September 24, 2019.
[14] Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs. 2004; 64 (12): 1339-58.
[15] Sanjay Kalra, Silver Bahendeka, Rakesh Sahay, Sujoy Ghosh, Fariduddin Md, Abbas Orabi et al. Consensus Recommendations on Sulfonylurea and Sulfonylurea Combinations in the Management of Type 2 Diabetes Mellitus – International Task Force. Indian J Endocrinol Metab. 2018 Jan-Feb; 22 (1): 132–157.
[16] Antonios Douros, Hui Yin, Oriana Hoi Yun Yu, Kristian B. Filion, Laurent Azoulay and Samy Suissa. Pharmacologic Differences of Sulfonylureas and the Risk of Adverse Cardiovascular and Hypoglycemic Events. Diabetes Care 2017 Nov; 40 (11): 1506-1513.
[17] Oriana Yu, Laurent Azoulay, Hui Yin, Kristian B. Filion, Samy Suissa. Sulfonylureas as Initial Treatment for Type 2 Diabetes and the Risk of Severe Hypoglycemia. The American Journal of Medicine. March 2018 Volume 131, Issue 3, Pages 317.
[18] Judith van Dalem, Martijn C G J Brouwers, Coen D A Stehouwer, André Krings, Hubert G M Leufkens, Johanna H M Driessen, Frank de Vries, Andrea M Burden. Risk of hypoglycaemia in users of sulphonylureas compared with metformin in relation to renal function and sulphonylurea metabolite group: population based cohort study BMJ 2016; 354: i3625.
[19] Schloot NC, Haupt A, Schütt M, Badenhoop K, Laimer M, Nicolay C, Reaney M et al. Risk of severe hypoglycemia in sulfonylurea-treated patients from diabetes centers in Germany/Austria: How big is the problem? Which patients are at risk? Diabetes Metab Res Rev. 2016 Mar; 32 (3): 316-24.
[20] Won Chul Ha, Su Jin Oh, Ji Hyun Kim, Jung Min Lee, Sang Ah Chang, Tae Seo Sohn et \ al. Severe Hypoglycemia Is a Serious Complication and Becoming an Economic \ Burden \ in Diabetes. Diabetes Metab J. 2012 Aug; 36 (4): 280–284.
[21] Nicola N. Zammitt, and Brian M. Frier. Hypoglycemia in Type 2 Diabetes Pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care 2005 Dec; 28 (12): 2948-2961.
[22] Ademolu AB, Ademolu AO, Ogbera AO, Fasanmade OA. (2015) Hypoglycemia in lkorodu. Journal of Asian Health.
[23] Ademolu AB (2017) Role of Ademolus Classification of Hypoglycemia in Blood Glucose and Diabetes Mellitus Management. Gastroenterol Liver Clin Med (2017) 1: 1 003.
[24] Adegbenga B Ademolu (2019) Analysis of Hypoglycemic Episodes in Diabetics in Africans Using Ademolus Classification of Hypoglycemia (ACH). Acta Scientific Medical Sciences 3 (3): 138-145.
[25] Iciar Martín-Timón and Francisco Javier del Cañizo-Gómez. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes. 2015 Jul 10; 6 (7): 912–926.
[26] Peter R. Shewry and Sandra J. Hey. The contribution of wheat to human diet and health. Food Energy Secur. 2015 Oct; 4 (3): 178–202.
[27] Clemens KK, McArthur E, Dixon SN, Fleet JL, Hramiak I, Garg AX. The Hypoglycemic Risk of Glyburide (Glibenclamide) Compared with Modified-Release Gliclazide. Can J Diabetes. 2015 Aug; 39 (4): 308-16.
[28] Bo Ahrén, James Edward Foley, Sylvie Dejager, Mouna Akacha, Qing Shao, Guenter Heimann, Markus Dworak, and Anja Schweizer. Higher Risk of Hypoglycemia with Glimepiride Versus Vildagliptin in Patients with Type 2 Diabetes is not Driven by High Doses of Glimepiride: Divergent Patient Susceptibilities? Diabetes Ther. 2014 Dec; 5 (2): 459–469.
[29] Arshad Hussain, Iftikhar Ali, Aziz Ullah Khan, and Tahir Mehmood Khan. Glibenclamide-induced profound hypoglycaemic crisis: a case report. Ther Adv Endocrinol Metab. 2016 Apr; 7 (2): 84–87.
[30] FDA approves first treatment for severe hypoglycemia that can be administered without an injection. July 24, 2019.
[31] Pilar I Beato-Víbora, and Francisco J Arroyo-Díez, New uses and formulations of glucagon for hypoglycaemia. Drugs Context. 2019; 8: 212599.
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  • APA Style

    Adegbenga Bolanle Ademolu. (2019). Sulfonylureas Induced Hypoglycemia in Diabetics - A Review. International Journal of Diabetes and Endocrinology, 4(4), 108-112. https://doi.org/10.11648/j.ijde.20190404.14

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    ACS Style

    Adegbenga Bolanle Ademolu. Sulfonylureas Induced Hypoglycemia in Diabetics - A Review. Int. J. Diabetes Endocrinol. 2019, 4(4), 108-112. doi: 10.11648/j.ijde.20190404.14

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    AMA Style

    Adegbenga Bolanle Ademolu. Sulfonylureas Induced Hypoglycemia in Diabetics - A Review. Int J Diabetes Endocrinol. 2019;4(4):108-112. doi: 10.11648/j.ijde.20190404.14

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  • @article{10.11648/j.ijde.20190404.14,
      author = {Adegbenga Bolanle Ademolu},
      title = {Sulfonylureas Induced Hypoglycemia in Diabetics - A Review},
      journal = {International Journal of Diabetes and Endocrinology},
      volume = {4},
      number = {4},
      pages = {108-112},
      doi = {10.11648/j.ijde.20190404.14},
      url = {https://doi.org/10.11648/j.ijde.20190404.14},
      eprint = {https://download.sciencepg.com/pdf/10.11648.j.ijde.20190404.14},
      abstract = {Diabetes is a metabolic disorder of glucose characterized by glucotoxicity, lipotoxicity and insulin resistance. In insulin resistance states, a higher level of insulin is needed to generate the usual body response to keep plasma glucose at physiologic level. The type 2 diabetics with insulin resistance cannot keep plasma glucose normal not because of absolute insulin deficiency but due to a relative deficiency as insulin is now required at a higher plasma level to achieve a near physiological or physiological plasma glucose level. Hence the need for a chemical agent to increase insulin secretion from the pancreatic beta cells at pharmacological dose (insulin secretagogues) was conceptualized and arrived at. Sulfonylureas are insulin secretagogues. Two generations of sulfonylurea’s are in use. The first and second. The class effects of sulfonylurea include weight gain, allergic reaction and hypoglycemia. But not enough emphasis is placed on the severity and grading of the hypoglycemia complicating use of sulfonylureas. Meanwhile hypoglycemia induced by sulfonylurea use is of various degree, severity and duration. The classification of hypoglycemia into grades in ADEMOLUS CLASSIFICATION OF HYPOGLYCEMIA makes it easier for scientist to understand, compare and monitor the severity of sulfonylureas. Mrs KFO is a 67 years old diabetic diagnosed over 8 years ago. She had asymptomatic hypoglycemia with a glucometer reading low (ADEMOLUS PHENOMENON) on a clinic day visit. She had been on glimepiride for three years. Mrs A. F. is a 75 years old diabetic diagnosed 4 years prior to presentation. She had a glucometer reading of low during a random blood sugar check at 8pm on day 2 of admission with associated general body weakness. She was on metformin and glibenclamide. Mrs. I E is a 72 years old diabetic who had a glucometer reading of low during her outpatient clinic visit. She was on gliclazide. Sulfonylureas use has been shown by these cases to be associated with symptomatic and asymptomatic very severe hypoglycemia. A possibility of synthesizing a new equally potent third generation of sulfonylureas with minimal or no hypoglycemic effect should be looked into.},
     year = {2019}
    }
    

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Author Information
  • Medicine Department, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria

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