title: Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes.
abstract: BACKGROUND
  Insulin-like growth factor-binding protein 7 (IGFBP-7) is able to interact with insulin-like growth factor 1 (IGF-1) as well as insulin. Previous studies have suggested that serum IGFBP-7 levels may be associated with insulin resistance in type 2 diabetes (T2D). This study aimed to evaluate IGFBP-7 serum protein and IGFBP7 DNA methylation levels in the subjects with and without T2D.
  
  
  RESULTS
  A total of 340 Swedish subjects including 100 newly diagnosed T2D patients (50 women/50 men), 100 age-matched nondiabetic control subjects (50/50) and 140 treated T2D patients (54/86) were studied. Serum IGFBP-7 levels were measured with a novel ELISA. IGF1, IGFBP-1, and insulin were determined by in-house radioimmunoassays. DNA methylation levels in the IGFBP7 gene were analyzed with a bisulfite-pyrosequencing technique. Serum IGFBP-7 protein levels were similar among nondiabetic subjects, newly diagnosed, and treated T2D patients and were not correlated with IGFBP7 DNA methylation. However, IGFBP7 DNA methylation was increased in men with newly diagnosed T2D compared with nondiabetic controls (17.6% vs. 12.5%, P < 0.01). Serum IGFBP-7 levels correlated (r = 0.331, P = 0.019) with serum IGFBP-1 levels, a marker of insulin production, in men but not women with newly diagnosed T2D.
  
  
  CONCLUSIONS
  This study demonstrates for the first time that IGFBP7 DNA methylation levels are increased in Swedish men with newly diagnosed T2D. The correlation between IGFBP-7 and IGFBP-1 suggests that low IGFBP-7 may be associated with insulin resistance in T2D.
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm SE-171 76, Sweden. harvest.gu@ki.se.
authors.forename: Harvest F
authors.initials: HF
authors.lastname: Gu
authors.forename: Tianwei
authors.initials: T
authors.lastname: Gu
authors.forename: Agneta
authors.initials: A
authors.lastname: Hilding
authors.forename: Yiming
authors.initials: Y
authors.lastname: Zhu
authors.forename: Lars
authors.initials: L
authors.lastname: Kärvestedt
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Ostenson
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kutsukake
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tamura
authors.forename: Kerstin
authors.initials: K
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