TY - JOUR
T1 - Sustained pro-inflammatory effects of hypoglycemia in people with type 2 diabetes and in people without diabetes
AU - Verhulst, Clementine E. M.
AU - van Heck, Julia I. P.
AU - Fabricius, Therese W.
AU - Stienstra, Rinke
AU - Teerenstra, Steven
AU - McCrimmon, Rory j.
AU - Tack, Cees J.
AU - Pedersen-Bjergaard, Ulrik
AU - de Galan, Bastiaan E.
AU - Hypo-RESOLVE Consortium
N1 - Funding Information:
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.
Publisher Copyright:
© 2022 by the American Diabetes Association.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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/m
2) underwent a hyperinsulinemiceuglycemic (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 1week. 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-a and interleukin 1b, 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.
AB - 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/m
2) underwent a hyperinsulinemiceuglycemic (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 1week. 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-a and interleukin 1b, 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.
KW - Hypoglycemia
KW - clamp
KW - T2DM
KW - diabetes
KW - inflammatory
KW - atherosclerosis
UR - http://www.scopus.com/inward/record.url?scp=85142403140&partnerID=8YFLogxK
U2 - 10.2337/db22-0246
DO - 10.2337/db22-0246
M3 - Article
C2 - 35848804
SN - 0012-1797
VL - 71
SP - 2716
EP - 2727
JO - Diabetes
JF - Diabetes
IS - 12
ER -