title: Urine metabolomics combined with the personalized diagnosis guided by Chinese medicine reveals subtypes of pre-diabetes.
abstract: The prevalence of type 2 diabetes continuously increases globally. A personalized strategy applied in the pre-diabetic stage is vital for diabetic prevention and management. The personalized diagnosis of Chinese Medicine (CM) may help to stratify the diabetics. Metabolomics is regarded as a potential platform to provide biomarkers for disease-subtypes. We designed an explorative study of 50 pre-diabetic males, combining GC-MS urine metabolomics with CM diagnosis in order to identify diagnostic biomarkers for pre-diabetic subtypes. Three CM physicians reached 85% diagnosis consistency resulting in the classification of 3 pre-diabetic groups. The urine metabolic patterns of groups 1 'Qi-Yin deficiency' and 2 'Qi-Yin deficiency with dampness' (subtype A) and group 3 'Qi-Yin deficiency with stagnation' (subtype B) were clearly discriminated. The majority of metabolites (51%), mainly sugars and amino acids, showed higher urine levels in subtype B compared with subtype A. This indicated more disturbances of carbohydrate metabolism and renal function in subtype B compared with subtype A. No differences were found for hematological and biochemical parameters except for levels of glucose and γ-glutamyltransferase that were significantly higher in subtype B compared with subtype A. This study proved that combining metabolomics with CM diagnosis can reveal metabolic signatures for pre-diabetic subtypes. The identified urinary metabolites may be of special clinical relevance for non-invasive screening for subtypes of pre-diabetes, which could lead to an improvement in personalized interventions for diabetics.
authors.affiliation: Department of Earth, Environmental and Life Science, TNO and Sino-Dutch Center for Preventive and Personalized Medicine, Utrechtseweg 48, P.O. Box 360, 3700 AJ, Zeist, The Netherlands.
authors.forename: Heng
authors.initials: H
authors.lastname: Wei
authors.forename: Wilrike
authors.initials: W
authors.lastname: Pasman
authors.forename: Carina
authors.initials: C
authors.lastname: Rubingh
authors.forename: Suzan
authors.initials: S
authors.lastname: Wopereis
authors.forename: Marc
authors.initials: M
authors.lastname: Tienstra
authors.forename: Jan
authors.initials: J
authors.lastname: Schroen
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.forename: Elwin
authors.initials: E
authors.lastname: Verheij
authors.forename: Jan
authors.initials: J
authors.lastname: van der Greef
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000145:classification / Q000175:diagnosis / Q000652:urine; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D057285:Precision Medicine; D011236:Prediabetic State / Q000145:classification / Q000175:diagnosis* / Q000652:urine*; D025341:Principal Component Analysis; D013577:Syndrome