Jumana Y Al-Aama,1,2 Hadiah B Al Mahdi,1 Mohammed A Salama,1 Khadija H Bakur,1,2 Amani Alhozali,3 Hala H Mosli,3 Suhad M Bahijri,4 Ahmed Bahieldin,5,6 Lothar Willmitzer,7 Sherif Edris1,5,6

1King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSA; 2King Abdulaziz University Faculty of Medicine, Department of Genetic Medicine, Jeddah, KSA; 3King Abdulaziz University, Faculty of Medicine, Department of Endocrinology and Metabolism, Jeddah, KSA; 4King Abdulaziz University, Faculty of Medicine, Department of Clinical Biochemistry, Jeddah, KSA; 5King Abdulaziz University, Faculty of Science, Biological Sciences Department, Jeddah, KSA; 6Ain Shams University, Department of Genetics, Cairo, Egypt; 7Max-Planck-Institut Fr Molekulare Pflanzenphysiologie, Molecular Physiology, Golm, DE, Germany

Correspondence: Sherif Edris; Jumana Y Al-AamaKing Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSATel +966 593 66 23 84Email seedris@kau.edu.sa; jalama@kau.edu.sa

Background: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D.Methods: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC.Results: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely glucagon signaling, glycine, serine and threonine and bile secretion. Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study.Conclusion: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.

Keywords: glucagon signaling, glycine production, bile secretion, insulin sensitivity/resistance

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