Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

Haya Al-Sulaiti, Ilhame Diboun, Maha V. Agha, Fatima F.S. Mohamed, Stephen Atkin, Alex S. Dömling, Mohamed A. Elrayess, Nayef A. Mazloum

Research output: Contribution to journalArticle

Abstract

Background: Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods: In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results: Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion: This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

Original languageEnglish
Article number348
JournalJournal of translational medicine
Volume17
Issue number1
DOIs
Publication statusPublished - 22 Oct 2019

Fingerprint

Medical problems
Type 2 Diabetes Mellitus
Insulin Resistance
Obesity
Insulin
Metabolites
Phospholipids
Glycerylphosphorylcholine
Metabolomics
Choline
Metabolic Networks and Pathways
Vascular Diseases
Comorbidity
Liver Diseases
Biomarkers
Liver
Serum
Association reactions

Keywords

  • Blood metabolites
  • Insulin resistance
  • Insulin sensitivity
  • Metabolomics
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Metabolic signature of obesity-associated insulin resistance and type 2 diabetes. / Al-Sulaiti, Haya; Diboun, Ilhame; Agha, Maha V.; Mohamed, Fatima F.S.; Atkin, Stephen; Dömling, Alex S.; Elrayess, Mohamed A.; Mazloum, Nayef A.

In: Journal of translational medicine, Vol. 17, No. 1, 348, 22.10.2019.

Research output: Contribution to journalArticle

Al-Sulaiti, Haya ; Diboun, Ilhame ; Agha, Maha V. ; Mohamed, Fatima F.S. ; Atkin, Stephen ; Dömling, Alex S. ; Elrayess, Mohamed A. ; Mazloum, Nayef A. / Metabolic signature of obesity-associated insulin resistance and type 2 diabetes. In: Journal of translational medicine. 2019 ; Vol. 17, No. 1.
@article{2501ff8f76314ba1b1674ade203c8411,
title = "Metabolic signature of obesity-associated insulin resistance and type 2 diabetes",
abstract = "Background: Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods: In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results: Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion: This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.",
keywords = "Blood metabolites, Insulin resistance, Insulin sensitivity, Metabolomics, Type 2 diabetes mellitus",
author = "Haya Al-Sulaiti and Ilhame Diboun and Agha, {Maha V.} and Mohamed, {Fatima F.S.} and Stephen Atkin and D{\"o}mling, {Alex S.} and Elrayess, {Mohamed A.} and Mazloum, {Nayef A.}",
year = "2019",
month = "10",
day = "22",
doi = "10.1186/s12967-019-2096-8",
language = "English",
volume = "17",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Metabolic signature of obesity-associated insulin resistance and type 2 diabetes

AU - Al-Sulaiti, Haya

AU - Diboun, Ilhame

AU - Agha, Maha V.

AU - Mohamed, Fatima F.S.

AU - Atkin, Stephen

AU - Dömling, Alex S.

AU - Elrayess, Mohamed A.

AU - Mazloum, Nayef A.

PY - 2019/10/22

Y1 - 2019/10/22

N2 - Background: Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods: In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results: Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion: This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

AB - Background: Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods: In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results: Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion: This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

KW - Blood metabolites

KW - Insulin resistance

KW - Insulin sensitivity

KW - Metabolomics

KW - Type 2 diabetes mellitus

UR - http://www.scopus.com/inward/record.url?scp=85073746865&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073746865&partnerID=8YFLogxK

U2 - 10.1186/s12967-019-2096-8

DO - 10.1186/s12967-019-2096-8

M3 - Article

C2 - 31640727

AN - SCOPUS:85073746865

VL - 17

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 348

ER -