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

Abstract

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)+], 3α,7α-dihydroxy-5β-cholestane [m/z 443.33, (M+K)+], 4α-methylzymosterol-4-carboxylate [m/z 425.34, (M+H‑H2O)+], 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.

Progress in Metabonomics of Type 2 Diabetes Mellitus

“…Although the clear relationships between phospholipids and T2DM have not been elucidated, current studies suggest that the change in phospholipids may be an early factor in the pathogenesis of T2DM. Lee Y et al [ 80 ] found that the cholesterol biosynthetic pathway was important in the development of T2DM. The T2DM group had a higher cholesterol level.…”

Acute aerobic exercise reveals that FAHFAs distinguish the metabolomes of overweight and normal-weight runners

“…Therefore, untargeted metabolomics provides a unique opportunity to discover new biomarkers (34)(35)(36)(37).…”

Application of Metabolomics in Various Types of Diabetes

“… 31 Among them, the cholesterol synthesis pathway occupies an important position in T2D. 32 Both systemic and local lipid metabolisms are altered. 6 Li et al used gas chromatography/time-of-flight mass spectrometry (GC´GC-TOFMS) combined with pattern recognition to analyze the plasma of diabetic patients and normal people in a control experiment.…”