Sang-Guk Lee (Presenter)
Yonsei University College of Medicine
Authorship: John Hoon Rim, Jong Rak Choi, Sang-Guk Lee
Department of Laboratory Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, South Korea
| Short Abstract We measured 188 metabolites including acylcarnitines, amino acids, biogenic amines, glycerophospho- and sphingolipids, and hexose with the AbsoluteIDQ p180 kit from Biocrates Life Science using Agilent HPLC 1260 and AB Sciex 5500 QTrap in five patients with T2DM and five healthy controls. Each 188 metabolites were compared by Mann-Whitney test. We found eighteen statistically different metabolites, six metabolites increased and twelve metabolites decreased in patients with T2DM. In addition, the patients with T2DM and healthy controls were separated with little over-lap using principal component analysis. Especially branched chain amino acid, leucine, isoleucine and valine were increased in patients with T2DM. |
Long Abstract
Introduction
Diabetes mellitus (DM) is a complex endocrine and metabolic disorder characterised by hyperglycemia [1]. It is one of the most rapidly increasing diseases worldwide, in Korea about 9.9% of the population (2.8 million people) suffered from DM according to the KNHANES 2007-2009 [2]. Type 2 DM (T2DM), the most common type of DM, is a heterogeneous and progressive disorder with variable degrees of insulin resistance and pancreatic β cells dysfunction, which resulted from several genetic and environmental factors such as obesity, low exercise, high calorie intake and stress [3].
In contrast to high prevalence of T2DM, significant proportions of individuals with T2DM are unaware of their hyperglycemia. The duration of T2DM is recognized as an important predictor of complication, early screening and detection is important to decrease risk of complication. Recently, several studies have reported some metabolites are correlated with insulin resistance and T2DM, and these metabolomic shifts have been identified 10-15 years before the onset of the disease. Therefore, more early markers of T2DM even before the occurrence of hyperglycemia are needed. Emerging metabolomics technologies allow metabolites involved in disease pathophysiology to be discovered by monitoring metabolites level changes in predisposed individuals compared with healthy controls. Thus we tried to find metabolomic signature of T2DM compared with healthy controls using a commercial metabolomics platform and mass spectrometry.
Methods and Results
We measured 188 metabolites from five analyte groups: acylcarnitines, amino acids, biogenic amines, glycerophospho- and sphingolipids, and hexose with the AbsoluteIDQ p180 kit from Biocrates Life Science using Agilent HPLC 1260 and AB Sciex 5500 QTrap in five patients with T2DM and five healthy controls. Each 188 metabolites were compared by Mann-Whitney test. We found eighteen statistically different metabolites, six metabolites (hexose, leucine, valine, isoleucine, phosphatidylcholine diacyl C36:5, and phosphatidylcholine diacyl C40:5) increased and twelve metabolites (hydroxypropionyl-L-carnitine, methylmalonyl-L-carnitine/hydroxyvaleryl-L-carnitine, propenyl-L-carnitine, glycine, threonine, phosphatidylcholine diacyl C30:2, phosphatidylcholine acyl-alkyl C44:5, sphingomyeline C22:3, methylglutaryl-L-carnitine, glutaconyl-L-carnitine, lysophosphatidylcholine acyl C18:2 and hydroxysphingomyeline C14:1) decreased in patients with T2DM. In addition, the patients with T2DM and healthy controls were separated with little over-lap using principal component analysis. Especially branched chain amino acid (BCAA), leucine, isoleucine, valine and tyrosine were increased in patients with T2DM. Elevated levels of the BCAA as well as some aromatic amino acids (tyrosine and phenylalanine) were also reported by other previous studies [4,5]. Decrease of glycine and lysophophatidylcholine acyl C18:2 in patients with T2DM also consistent with previous reports [5,6]. However, we observed decrease of C3 and C5 acylcarnitines levels in T2DM although previous studies reported the significant and specific increase of C3 and C5 acylcarnitines levels in T2DM [7,8].
Conclusions
We found BCAA and tyrosine were increased in T2DM while glycine and lysophophatidylcholine acyl C18:2 were decreased in T2DM. Further large population studies including T2DM, pre-diabetes, and healthy controls are needed to determined metabolic signature of insulin resistance and T2DM.
References & Acknowledgements:
References
[1] Tahrani AA, Bailey CJ, Del Prato S, Barnett AH. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011;378:182-197.
[2] Kim DJ. The epidemiology of diabetes in Korea. Diabetes Metab J 2011;35:303-308.
[3] Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 2005;365:1333-1346.
[4] Wang TJ, Larson MG, Vasan RS, et al. Metabolite profiles and the risk of developing diabetes. Nat Med 2011;17:448-453.
[5] Sas KM, Karnovsky A, Michailidis G, Pennathur S. Metabolomics and diabetes: analytical and computational approaches. Diabetes 2015;64:718-732.
[6] Wang-Sattler R, Yu Z, Herder C, et al. Novel biomarkers for pre-diabetes identified by metabolomics. Mol Syst Biol 2012;8:615.
[7] Newgard CB, An J, Bain JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009;9:311-326.
[8] Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab 2012;15:606-614.
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