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Sustained pro-inflammatory effects of hypoglycemia in people with type 2 diabetes and in people without diabetes

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posted on 18.07.2022, 12:41 authored by 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

Iatrogenic hypoglycaemia 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. Fifteen adults with type 2 diabetes and 16 matched controls (M/F 17/14, 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 one week. The proportion of CD16+-monocytes increased, and the proportion of CD14+-monocytes decreased, which sustained for a week in people without diabetes. During hypoglycemia, ex vivo stimulated, monocytes released more TNF-α and IL-1β, and less IL-10, particularly in people with diabetes. Hs-CRP and 25 circulating inflammatory proteins increased, remaining significantly elevated one 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 pro-inflammatory response at the cellular and protein level that is sustained for one week in people with type 2 diabetes and controls.  


This study has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777460. The JU receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and T1D Exchange, JDRF, International Diabetes Federation (IDF), The Leona M. and Harry B. Helmsley Charitable Trust.