Identification of serum metabolome signatures associated with retinal and renal complications of type 2 diabetes
Yoshihiko Tomofuji, Ken Suzuki, Toshihiro Kishikawa, Nobuhiro Shojima, Jun Hosoe, Kyoko Inagaki, Sunao Matsubayashi, Hisamitsu Ishihara, Hirotaka Watada, Yasushi Ishigaki, The BioBank Japan Project, Yuji Yamanashi, Yoichi Furukawa, Takayuki Morisaki, Yoichiro Kamatani, Kaori Muto, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Daisuke Obata, Masahiko Higashiyama, Akihide Masumoto, Yukihiro Koretsune, Hidenori Inohara, Yoshinori Murakami, Koichi Matsuda, Yukinori Okada, Toshimasa Yamauchi, Takashi Kadowaki
Abstract
BACKGROUND: Type 2 diabetes is a common disease around the world and its major complications are diabetic retinopathy (DR) and diabetic kidney disease (DKD). Persons with type 2 diabetes with complications, especially who have both DR and DKD, have poorer prognoses than those without complications. Therefore, prevention and early identification of the complications of type 2 diabetes are necessary to improve the prognosis of persons with type 2 diabetes. The aim of this study is to identify factors associated with the development of multiple complications of type 2 diabetes. METHODS: We profiled serum metabolites of persons with type 2 diabetes with both DR and DKD (N = 141) and without complications (N = 159) using a comprehensive non-targeted metabolomics approach with mass spectrometry. Based on the serum metabolite profiles, case-control comparisons and metabolite set enrichment analysis (MSEA) were performed. RESULTS: ) are significantly increased in those with the complications. MSEA identifies fatty acid biosynthesis as the type 2 diabetes complications-associated biological pathway (P = 0.0020). CONCLUSIONS: Our metabolome analysis identifies the serum metabolite features of the persons with type 2 diabetes with multiple complications, which could potentially be used as biomarkers.