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High-resolution metabolomics determines the mode of onset of type 2 diabetes in a 3-year prospective cohort study

 Yeseung Lee  ;  Aryo Dimas Pamungkas  ;  Carl Angelo D Medriano  ;  Jinsung Park  ;  Seri Hong  ;  Sun Ha Jee  ;  Youngja H Park 
 International Journal of Molecular Medicine, Vol.41(2) : 1069-1077, 2018 
Journal Title
 International Journal of Molecular Medicine 
Issue Date
Adult ; Age of Onset ; Biomarkers/*blood ; Cholesterol/biosynthesis/*blood ; Type 2/epidemiology/genetics/*metabolism/pathology Diabetes Mellitus ; Female ; Humans ; Male ; Metabolic Networks and Pathways/genetics ; *Metabolomics ; Middle Aged ; Republic of Korea/epidemiology ; Tandem Mass Spectrometry
Type 2 diabetes mellitus (DM) is a progressive disease and the rate of progression from non-diabetes to DM varies considerably between individuals, ranging from a few months to many years. It is important to understand the mechanisms underlying the progression of diabetes. In the present study, a high-resolution metabolomics (HRM) analysis was performed to detect potential biomarkers and pathways regulating the mode of onset by comparing subjects who developed and did not develop type 2 DM at the second year in a 3-year prospective cohort study. Metabolic profiles correlated with progression to DM were examined. The subjects (n=98) were classified into four groups: Control (did not develop DM for 3 years), DM (diagnosed with DM at the start of the study), DM onset at the third year and DM onset at the second year. The focus was on the comparison of serum samples of the DM groups with onset at the second and third year from the first year, where these two groups had not developed DM, yet. Analyses involved sample examination using liquid chromatography-mass spectrometry-based HRM and multivariate statistical analysis of the data. Metabolic differences were identified across all analyses with the affected pathways involved in metabolism associated with steroid biosynthesis and bile acid biosynthesis. In the first year, higher levels of cholesterol {mass-to charge ratio (m/z) 369.35, (M+H-H2O)+}, 25-hydroxycholesterol [m/z 403.36, (M+H)+], 3alpha,7alpha-dihydroxy-5beta-cholestane [m/z 443.33, (M+K)+], 4alpha-methylzymosterol-4-carboxylate [m/z 425.34, (M+HH2O)+], and lower levels of 24,25-dihydrolanosterol [m/z 429.40, (M+H)+] were evident in the group with DM onset at the second year compared with those in the group with DM onset at the third year. These results, with a focus on the cholesterol biosynthesis pathway, point to important aspects in the development of DM and may aid in the development of more effective means of treatment and prevention.
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1. Journal Papers (연구논문) > 4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원)
Yonsei Authors
지선하(Jee, Sun Ha)
홍세리(Hong, Se Ri)
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