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This change in longevity and duration of diabetes coupled with significant advances in therapeutic options for patients has fundamentally changed the landscape of diabetes management, particularly in patients with type 1 diabetes mellitus. However, hypoglycemia remains a major barrier to achieving optimal glycemic control. Current understanding of the mechanisms of hypoglycemia has expanded to include not only counter\u2010regulatory hormonal responses but also direct changes in brain glucose, fuel sensing, and utilization, as well as changes in neural networks that modulate behavior, mood, and cognition. Different strategies to prevent and treat hypoglycemia have been developed, including educational strategies, new insulin formulations, delivery devices, novel technologies, and pharmacologic targets. This review article will discuss current literature contributing to our understanding of the myriad of factors that lead to the development of clinically meaningful hypoglycemia and review established and novel therapies for the prevention and treatment of hypoglycemia.<\/jats:p>","DOI":"10.1111\/nyas.14904","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T22:15:31Z","timestamp":1665094531000},"page":"25-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pathophysiology and management of hypoglycemia in diabetes"],"prefix":"10.1111","volume":"1518","author":[{"given":"Elizabeth","family":"Sanchez\u2010Rangel","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Section of Endocrinology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelani","family":"Deajon\u2010Jackson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Endocrinology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice Jin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Endocrinology Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Division of Endocrinology, Department of Internal Medicine University of North Carolina \u2013 Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"issue":"3","key":"e_1_2_7_2_1","first-page":"141","article-title":"Pancreatic extracts in the treatment of diabetes mellitus","volume":"12","author":"Banting F. 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