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

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

doi:10.1186/s12967-019-2096-8

Abstract

BackgroundObesity 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.MethodsIn 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.ResultsOur 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.ConclusionThis 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.

Highlights

Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM)
Previous studies have suggested that lower levels of inflammatory mediators play a role in the protective phenotype of obese insulin sensitive (OIS) individuals compared to their pathologically obese counterparts, known as obese insulin resistant (OIR) individuals [6,7,8]
General characteristics of participants Thirty-two lean (BMI = 22.7 ± 2.5 kg/m2, all females) and seventy-five obese and morbidly obese (BMI = 45 ± 6.7 kg/m2, 45 females and 30 males) individuals were recruited at Hamad Medical Corporation and Al Emadi hospital, respectively

Summary

Introduction

Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Previous studies have suggested that lower levels of inflammatory mediators play a role in the protective phenotype of obese insulin sensitive (OIS) individuals compared to their pathologically obese counterparts, known as obese insulin resistant (OIR) individuals [6,7,8]. Other reports have suggested that OIS individuals show fewer markers of oxidative stress [8, 9] These two mediators (inflammation and oxidative stress) could potentially be influenced by various genetic and environmental factors [10]. Evidence of the genetic component remains limited, the environmental effect of certain pollutants and various medications has been previously established [11, 12]

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