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Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Kahal, Hassan; Halama, Anna; Aburima, Ahmed; Bhagwat, Aditya M.; Butler, Alexandra E.; Grauman, Johannes; Suhre, Karsten; Sathyapalan, Thozhukat; Atkin, Stephen L.


Hassan Kahal

Anna Halama

Aditya M. Bhagwat

Alexandra E. Butler

Johannes Grauman

Karsten Suhre

Stephen L. Atkin


Intensive diabetes control has been associated with increased mortality in type 2 diabetes (T2DM); this has been suggested to be due to increased hypoglycemia. We measured hypoglycemia-induced changes in endothelial parameters, oxidative stress markers and inflammation at baseline and after a 24-hour period in type 2 diabetic (T2DM) subjects versus age-matched controls. Case-control study: 10 T2DM and 8 control subjects. Blood glucose was reduced from 5 (90 mg/dl) to hypoglycemic levels of 2.8 mmol/L (50 mg/dl) for 1 hour by incremental hyperinsulinemic clamps using baseline and 24 hour samples. Measures of endothelial parameters, oxidative stress and inflammation at baseline and at 24-hours post hypoglycemia were performed: proteomic (Somalogic) analysis for inflammatory markers complemented by C-reactive protein (hsCRP) measurement, and proteomic markers and urinary isoprostanes for oxidative measures, together with endothelial function. Between baseline and 24 -hours after hypoglycemia, 15 of 140 inflammatory proteins differed in T2DM whilst only 1 of 140 differed in controls; all returned to baseline at 24-hours. However, elevated hsCRP levels were seen at 24-hours in T2DM (2.4 mg/L (1.2–5.4) vs. 3.9 mg/L (1.8–6.1), Baseline vs 24-hours, P < 0.05). In patients with T2DM, between baseline and 24-hour after hypoglycemia, only one of 15 oxidative stress proteins differed and this was not seen in controls. An increase (P = 0.016) from baseline (73.4 ng/mL) to 24 hours after hypoglycemia (91.7 ng/mL) was seen for urinary isoprostanes. Hypoglycemia resulted in inflammatory and oxidative stress markers being elevated in T2DM subjects but not controls 24-hours after the event.


Kahal, H., Halama, A., Aburima, A., Bhagwat, A. M., Butler, A. E., Grauman, J., …Atkin, S. L. (2020). Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects. Scientific reports, 10(1), Article 4750.

Journal Article Type Article
Acceptance Date Feb 28, 2020
Online Publication Date Mar 16, 2020
Publication Date 2020-12
Deposit Date Mar 24, 2020
Publicly Available Date Mar 25, 2020
Journal Scientific Reports
Print ISSN 2045-2322
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 10
Issue 1
Article Number 4750
Keywords Diabetes complications; Type 2 diabetes
Public URL
Publisher URL
Additional Information Received: 20 November 2019; Accepted: 28 February 2020; First Online: 16 March 2020; : The authors declare no competing interests.


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