title: Singlet oxygen induced products of linoleates, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE), can be potential biomarkers for early detection of type 2 diabetes.
abstract: Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F2α (8-iso-PGF2α), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF2α, HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), "high-normal" (fasting plasma glucose, 100-109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-α, high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)- HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10- and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and "high-normal" type without OGTT.
authors.affiliation: National Institute of Advanced Industrial Science and Technology, Takamatsu, Kagawa, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Umeno
authors.forename: Mototada
authors.initials: M
authors.lastname: Shichiri
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishida
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Abe
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kataoka
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Yoshino
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Hagihara
authors.forename: Nanako
authors.initials: N
authors.lastname: Aki
authors.forename: Makoto
authors.initials: M
authors.lastname: Funaki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Asada
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
mesh_terms: D054392:Adipokines / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D042241:Early Diagnosis; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005951:Glucose Tolerance Test; D006801:Humans; D008041:Linoleic Acids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D026082:Singlet Oxygen / Q000378:metabolism*
chemical_list: D054392:Adipokines; D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; C495366:hydroxyoctadecadienoic acid; D026082:Singlet Oxygen