Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes

Anna Halama, Hassan Kahal, Aditya Bhagwat, Jonas Zierer, Thozhukat Sathyapalan, Johannes Graumann, Karsten Suhre, Stephen Atkin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 Blood was withdrawn at four time points: at baseline after an overnight fast; after clamping to euglycaemia at 5 mmol/L; after clamping to hypoglycaemia at 2.8 mmol/L; and 24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.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
DOIs
Publication statusAccepted/In press - 1 Jan 2018

Fingerprint

Hypoglycemia
Proteomics
Type 2 Diabetes Mellitus
Insulin
Constriction
Fatty Acid-Binding Proteins
Control Groups
alpha-Linolenic Acid
Metabolomics
Linoleic Acid
Hypoglycemic Agents
Cyclic AMP
Adenosine
Hydrocortisone
Proteins
Fatty Acids

Keywords

  • clinical physiology
  • glucose metabolism
  • hypoglycaemia
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes. / Halama, Anna; Kahal, Hassan; Bhagwat, Aditya; Zierer, Jonas; Sathyapalan, Thozhukat; Graumann, Johannes; Suhre, Karsten; Atkin, Stephen.

In: Diabetes, Obesity and Metabolism, 01.01.2018.

Research output: Contribution to journalArticle

@article{ac01ef06ea26465d9cb5ad5770c5aeac,
title = "Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes",
abstract = "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.",
keywords = "clinical physiology, glucose metabolism, hypoglycaemia, type 2 diabetes",
author = "Anna Halama and Hassan Kahal and Aditya Bhagwat and Jonas Zierer and Thozhukat Sathyapalan and Johannes Graumann and Karsten Suhre and Stephen Atkin",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/dom.13602",
language = "English",
journal = "Diabetes, Obesity and Metabolism",
issn = "1462-8902",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Metabolic and proteomic signatures of hypoglycaemia in type 2 diabetes

AU - Halama, Anna

AU - Kahal, Hassan

AU - Bhagwat, Aditya

AU - Zierer, Jonas

AU - Sathyapalan, Thozhukat

AU - Graumann, Johannes

AU - Suhre, Karsten

AU - Atkin, Stephen

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - clinical physiology

KW - glucose metabolism

KW - hypoglycaemia

KW - type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85059143809&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059143809&partnerID=8YFLogxK

U2 - 10.1111/dom.13602

DO - 10.1111/dom.13602

M3 - Article

AN - SCOPUS:85059143809

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

SN - 1462-8902

ER -