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. 2019 Oct 22;17(1):348.
doi: 10.1186/s12967-019-2096-8.

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

Haya Al-Sulaiti  1 , Ilhame Diboun  2 , Maha V Agha  3 , Fatima F S Mohamed  3 , Stephen Atkin  3   4 , Alex S Dömling  1 , Mohamed A Elrayess  5 , Nayef A Mazloum  6
Affiliations

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

Haya Al-Sulaiti et al. J Transl Med. .

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.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Boxplot of metabolites that belong to the enriched phospholipid pathway differentiating OIS and OIR + T2DM groups. Linear regression was performed to identify significant metabolites differentiating OIS from OIR and T2DM using the R statistical package after correcting for age, gender, BMI and principle components (PC1 and PC2). Y-axis indicates levels of metabolites (log2). *p-value significance level of 0.05 was used
Fig. 2
Fig. 2
Boxplot of metabolites that belong to the enriched pathways associated with increased risk of obesity-associated insulin resistance and T2DM. Linear regression was performed to identify significant metabolites associated with disease progression using the R statistical package after correcting for age, gender, BMI and principle components (PC1 and PC2). Y-axis indicates levels of metabolites (log2). A p-value significance level of 0.05 was used
Fig. 3
Fig. 3
OPLS-DA model comparing metabolites from lean, OIS, OIR and T2DM individuals. a A score plot showing the class-discriminatory component 1 (x-axis) versus class-discriminatory component 2 (y-axis). b The corresponding loading plot showing enriched pathways’ associated metabolites differentiating OIS and OIR + T2DM groups or those associated with disease progression
See this image and copyright information in PMC

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