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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Most cited references 39

Record: found
Abstract: found
Article: not found

Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis

Marta Guasch-Ferré, Adela Hruby, Estefanía Toledo … (2016)

OBJECTIVE To conduct a systematic review of cross-sectional and prospective human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on prediabetes and type 2 diabetes. RESEARCH DESIGN AND METHODS We searched MEDLINE and EMBASE databases through August 2015. We conducted a qualitative review of cross-sectional and prospective studies. Additionally, meta-analyses of metabolite markers, with data estimates from at least three prospective studies, and type 2 diabetes risk were conducted, and multivariable-adjusted relative risks of type 2 diabetes were calculated per study-specific SD difference in a given metabolite. RESULTS We identified 27 cross-sectional and 19 prospective publications reporting associations of metabolites and prediabetes and/or type 2 diabetes. Carbohydrate (glucose and fructose), lipid (phospholipids, sphingomyelins, and triglycerides), and amino acid (branched-chain amino acids, aromatic amino acids, glycine, and glutamine) metabolites were higher in individuals with type 2 diabetes compared with control subjects. Prospective studies provided evidence that blood concentrations of several metabolites, including hexoses, branched-chain amino acids, aromatic amino acids, phospholipids, and triglycerides, were associated with the incidence of prediabetes and type 2 diabetes. We meta-analyzed results from eight prospective studies that reported risk estimates for metabolites and type 2 diabetes, including 8,000 individuals of whom 1,940 had type 2 diabetes. We found 36% higher risk of type 2 diabetes per study-specific SD difference for isoleucine (pooled relative risk 1.36 [1.24–1.48]; I 2 = 9.5%), 36% for leucine (1.36 [1.17–1.58]; I 2 = 37.4%), 35% for valine (1.35 [1.19–1.53]; I 2 = 45.8%), 36% for tyrosine (1.36 [1.19–1.55]; I 2 = 51.6%), and 26% for phenylalanine (1.26 [1.10–1.44]; I 2 = 56%). Glycine and glutamine were inversely associated with type 2 diabetes risk (0.89 [0.81–0.96] and 0.85 [0.82–0.89], respectively; both I 2 = 0.0%). CONCLUSIONS In studies using high-throughput metabolomics, several blood amino acids appear to be consistently associated with the risk of developing type 2 diabetes.

0 comments Cited 334 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Adult weight change and risk of postmenopausal breast cancer.

Bernard A Rosner, G. A. Colditz, A. Eliassen … (2006)

Endogenous hormones are a primary cause of breast cancer. Adiposity affects circulating hormones, particularly in postmenopausal women, and may be a modifiable risk factor for breast cancer. To assess the associations of adult weight change since age 18 years and since menopause with the risk of breast cancer among postmenopausal women. Prospective cohort study within the Nurses' Health Study. A total of 87,143 postmenopausal women, aged 30 to 55 years and free of cancer, were followed up for up to 26 years (1976-2002) to assess weight change since age 18 years. Weight change since menopause was assessed among 49,514 women who were followed up for up to 24 years. Incidence of invasive breast cancer. Overall, 4393 cases of invasive breast cancer were documented. Compared with those who maintained weight, women who gained 25.0 kg or more since age 18 years were at an increased risk of breast cancer (relative risk [RR], 1.45; 95% confidence interval [CI], 1.27-1.66; P<.001 for trend), with a stronger association among women who have never taken postmenopausal hormones (RR,1.98; 95% CI, 1.55-2.53). Compared with weight maintenance, women who gained 10.0 kg or more since menopause were at an increased risk of breast cancer (RR, 1.18; 95% CI, 1.03-1.35; P = .002 for trend). Women who had never used postmenopausal hormones, lost 10.0 kg or more since menopause, and kept the weight off were at a lower risk than those who maintained weight (RR, 0.43; 95% CI, 0.21-0.86; P = .01 for weight loss trend). Overall, 15.0% (95% CI, 12.8%-17.4%) of breast cancer cases in this population may be attributable to weight gain of 2.0 kg or more since age 18 years and 4.4% (95% CI, 3.6%-5.5%) attributable to weight gain of 2.0 kg or more since menopause. Among those who did not use postmenopausal hormones, the population attributable risks are 24.2% (95% CI, 19.8%-29.1%) for a weight gain since age 18 years and 7.6% (95% CI, 5.9%-9.7%) for weight gain since menopause. These data suggest that weight gain during adult life, specifically since menopause, increases the risk of breast cancer among postmenopausal women, whereas weight loss after menopause is associated with a decreased risk of breast cancer. Thus, in addition to other known benefits of healthy weight, our results provide another reason for women approaching menopause to maintain or lose weight, as appropriate.

0 comments Cited 172 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Metabolomics: an emerging but powerful tool for precision medicine

Clary Clish (2015)

Metabolomics, which is defined as the comprehensive analysis of metabolites in a biological specimen, is an emerging technology that holds promise to inform the practice of precision medicine. Historically, small numbers of metabolites have been used to diagnose complex metabolic diseases as well as monogenic disorders such as inborn errors of metabolism. Current metabolomic technologies go well beyond the scope of standard clinical chemistry techniques and are capable of precise analyses of hundreds to thousands of metabolites. Consequently, metabolomics affords detailed characterization of metabolic phenotypes and can enable precision medicine at a number of levels, including the characterization of metabolic derangements that underlie disease, discovery of new therapeutic targets, and discovery of biomarkers that may be used to either diagnose disease or monitor activity of therapeutics.

0 comments Cited 171 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Haya Al-Sulaiti: halsulaiti@adlqatar.qa

Ilhame Diboun: idibou01@mail.bbk.ac.uk

Maha V. Agha: mvn2001@qatar-med.cornell.edu

Fatima F. S. Mohamed: ffm2001@qatar-med.cornell.edu

Stephen Atkin: sla2002@qatar-med.cornell.edu

Alex S. Dömling: a.s.s.domling@rug.nl

Mohamed A. Elrayess: melrayess@adlqatar.qa , maelrayess@hotmail.com

Nayef A. Mazloum:

ORCID: http://orcid.org/0000-0002-1199-5272

nam2016@qatar-med.cornell.edu

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 22 October 2019

Publication date PMC-release: 22 October 2019

Publication date Collection: 2019

Volume: 17

Electronic Location Identifier: 348

Affiliations

[1 ]ISNI 0000 0004 0407 1981, GRID grid.4830.f, Department of Drug Design, , University of Groningen, ; A. Deusinglaan 1, 9713 AV Groningen, The Netherlands

[2 ]ISNI 0000 0004 4662 7175, GRID grid.452173.6, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), ; Doha, Qatar

[3 ]Weill Cornell Medicine-Qatar, Doha, Qatar

[4 ]Royal College of Surgeons, Ireland, Bahrain

[5 ]ISNI 0000 0004 0634 1084, GRID grid.412603.2, Biomedical Research Center (BRC), Qatar University, ; Doha, Qatar

Author information

Nayef A. Mazloum http://orcid.org/0000-0002-1199-5272

Article

Publisher ID: 2096

DOI: 10.1186/s12967-019-2096-8

PMC ID: 6805293

PubMed ID: 31640727

SO-VID: db70e3e0-0f78-41c1-a458-7517891a3912

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 3 July 2019

Date accepted : 11 October 2019

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100008982, Qatar National Research Fund;

Award ID: NPRP8-059-1-009

Award Recipient : Nayef A. Mazloum

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: metabolomics,blood metabolites,insulin sensitivity,insulin resistance,type 2 diabetes mellitus

Data availability:

ScienceOpen disciplines: Medicine

Keywords: metabolomics, blood metabolites, insulin sensitivity, insulin resistance, type 2 diabetes mellitus

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

Read this article at

Abstract

Background

Methods

Results

Conclusion

Related collections

Karger: Nutrition and Dietetics

Most cited references 39

Metabolomics in Prediabetes and Diabetes: A Systematic Review and Meta-analysis

Adult weight change and risk of postmenopausal breast cancer.

Metabolomics: an emerging but powerful tool for precision medicine

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 166

Cited by 44

Most referenced authors 887