Abstract
To determine the biochemical changes that underlie hypoglycaemia in a healthy control group and in people with type 2 diabetes (T2D). 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 Blood was withdrawn at four time points: at baseline after an overnight fast; after clamping to euglycaemia at 5 mmol/L; after clamping to hypoglycaemia at 2.8 mmol/L; and 24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. 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. 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.
Highlights
In healthy individuals, blood glucose levels are maintained within a narrow range by mechanisms that dynamically respond to starvation, food intake, physical exercise and physiological stresses
Fatty acid metabolism differentiates type 2 diabetes (T2D) from healthy individuals under hypoglycemia We identified 26 metabolites under hypoglycemia, which were differential between T2D and control
We have shown that insulin is the main trigger of the molecular responses, influencing predominantly fatty acid metabolism, which was impaired in T2D
Summary
Blood glucose levels are maintained within a narrow range by mechanisms that dynamically respond to starvation, food intake, physical exercise and physiological stresses. The objective of our study was to determine, for the first time, biochemical changes occurring in healthy individuals and patients with T2D under insulin induced euglycemic and hypoglycemic conditions as well as 24 hours after the challenge, using state-of-theart metabolomics based on a non-targeted profiling and proteomics approach enabling quantification of 1,125 proteins levels in blood plasma samples.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
