Biomarkers of Morbid Obesity and Prediabetes by Metabolomic Profiling of Human Discordant Phenotypes

Metabolomic studies aimed to dissect the connection between the development of type 2 diabetes and obesity are still scarce. In the present study, fasting serum from sixty-four adult individuals classified into four sex matched groups by their BMI [non-obese versus morbid obese] and the increased risk of developing diabetes [prediabetic insulin resistant state versus non-prediabetic non-insulin resistant] was analyzed by LC- and FIA-ESI-MS/MS-driven metabolomic approaches. Altered levels of [lyso]glycerophospholipids was the most specific metabolic trait associated to morbid obesity, particularly lysophosphatidylcholines acylated with margaric, oleic and linoleic acids [lysoPC C17:0: R = -0.56, p = 0.0003; lysoPC C18:1: R = -0.61, p = 0.0001; lysoPC C18:2 R = -0.64, p < 0.0001] Several amino acids were biomarkers of risk of diabetes onset associated to obesity. For instance, glutamate significantly associated with fasting insulin [R = 0.5,p = 0.0019] and HOMA-IR [R = 0.46,p = 0.0072], while glycine showed negative associations [fasting insulin: R = -0.51, p = 0.0017; HOMA-IR: R = -0.49, p = 0.0033], and the branched chain amino acid valine associated to prediabetes and insulin resistance in a BMI-independent manner [fasting insulin: R = 0.37,p = 0.0479; HOMA-IR: R = 0.37,p = 0.0468]. Minority sphingolipids including specific [dihydro]ceramides and sphingomyelins also associated with the prediabetic insulin resistant state, hence deserving attention as potential targets for early diagnosis or therapeutic intervention. (C) 2016 Elsevier B.V. All rights reserved.