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Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes

Halama, Anna; Kahal, Hassan; Bhagwat, Aditya M.; Zierer, Jonas; Sathyapalan, Thozhukat; Grauman, Johannes; Suhre, Karsten; Atkin, Stephen


Anna Halama

Hassan Kahal

Aditya M. Bhagwat

Jonas Zierer

Thozhukat Sathyapalan

Johannes Grauman

Karsten Suhre

Stephen Atkin


Aims: To determine the biochemical changes that underlie hypoglycaemia in a healthy control group and in people with type 2 diabetes (T2D). Materials and methods: We report a hypoglycaemic clamp study in seven healthy controls and 10 people with T2D. Blood was withdrawn at four time points: at baseline after an overnight fast; after clamping to euglycaemia at 5 mmol/L; after clamping to hypoglycaemia at 2.8 mmol/L; and 24 hours later, after overnight fast. Deep molecular phenotyping using non-targeted metabolomics and the SomaLogic aptamer-based proteomics platform was performed on collected samples. Results: A total of 955 metabolites and 1125 proteins were identified, with significant alterations in >90 molecules. A number of metabolites significantly increased during hypoglycaemia, but only cortisol, adenosine-3′,5′-cyclic monophosphate (cyclic AMP), and pregnenolone sulphate, were independent of insulin. By contrast, identified protein changes were triggered by hypoglycaemia rather than insulin. The T2D group had significantly higher levels of fatty acids including 10-nonadecenoate, linolenate and dihomo-linoleate during hypoglycaemia compared with the control group. Molecules contributing to cardiovascular complications such as fatty-acid-binding protein-3 and pregnenolone sulphate were altered in the participants with T2D during hypoglycaemia. Almost all molecules returned to baseline at 24 hours. Conclusions: The present study provides a comprehensive description of molecular events that are triggered by insulin-induced hypoglycaemia. We identified deregulated pathways in T2D that may play a role in the pathophysiology of hypoglycaemia-induced cardiovascular complications.


Graumann, J., Atkin, S. L., Halama, A., Kahal, H., Bhagwat, A. M., Zierer, J., …Atkin, S. (2019). Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes. Diabetes, Obesity and Metabolism, 21(4), 909-919.

Journal Article Type Article
Acceptance Date Nov 20, 2018
Online Publication Date Dec 7, 2018
Publication Date 2019-04
Deposit Date Dec 9, 2018
Publicly Available Date Dec 8, 2019
Journal Diabetes, Obesity and Metabolism
Print ISSN 1462-8902
Electronic ISSN 1463-1326
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 21
Issue 4
Pages 909-919
Keywords Internal Medicine; Endocrinology, Diabetes and Metabolism; Endocrinology
Public URL
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