Sustained Proinflammatory Effects of Hypoglycemia in People With Type 2 Diabetes and in People Without Diabetes

Clementine E.M. Verhulst*, Julia I.P. van Heck, Therese W. Fabricius, Rinke Stienstra, Steven Teerenstra, Rory J. McCrimmon, Cees J. Tack, Ulrik Pedersen-Bjergaard, Bastiaan E. de Galan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

Iatrogenic hypoglycemia activates the immune system and is associated with an increased risk for atherosclerotic disease. We determined acute and long-term effects of insulin-induced hypoglycemia on inflammatory markers in humans with or without type 2 diabetes. A total of 15 adults with type 2 diabetes and 16 matched control subjects (17 men and 14 women, age 59.6 ± 7.1 years, BMI 28.5 ± 4.3 kg/m2) underwent a hyperinsulinemic-euglycemic (5.31 ± 0.32 mmol/L) hypoglycemic (2.80 ± 0.12 mmol/L) glucose clamp. Blood was drawn during euglycemia and hypoglycemia and 1, 3, and 7 days later to determine circulating immune cell composition, function, and inflammatory proteins. In response to hypoglycemia, absolute numbers of circulating lymphocytes and monocytes significantly increased and remained elevated for 1 week. The proportion of CD16+ monocytes increased, and the proportion of CD14+ monocytes decreased, which was sustained for 1 week in people without diabetes. During hypoglycemia, ex vivo stimulated monocytes released more tumor necrosis factor-α and interleukin 1β, and less interleukin 10, particularly in people with diabetes. hs-CRP and 25 circulating inflammatory proteins increased, remaining significantly elevated 1 week after hypoglycemia. While levels at euglycemia differed, responses to hypoglycemia were broadly similar in people with or without type 2 diabetes. We conclude that hypoglycemia induces a proinflammatory response at the cellular and protein level that is sustained for 1 week in people with type 2 diabetes and control subjects.

Original languageEnglish
Pages (from-to)2716-2727
Number of pages12
JournalDiabetes
Volume71
Issue number12
DOIs
Publication statusPublished - Dec 2022

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