title: Epigenetic analyses of the insulin-like growth factor binding protein 1 gene in type 1 diabetes and diabetic nephropathy.
abstract: BACKGROUND
  Clinical observations have demonstrated that high levels of circulating insulin-like growth factor binding protein-1 (IGFBP-1) are associated with type 1 diabetes (T1D), whereas low serum IGFBP-1 levels are associated with the risk of type 2 diabetes (T2D). Recently, we reported that increased DNA methylation levels in the IGFBP1 gene were associated with T2D. In the present study, we evaluated the epigenetic changes of IGFBP1 in T1D and diabetic nephropathy (DN).
  
  
  RESULTS
  In total, 778 Swedish individuals, including T1D patients with or without DN and subjects with the normal glucose tolerance (NGT), were involved in the study. IGFBP1 methylation levels in genomic DNA extracted from peripheral blood were analyzed with bisulfite pyrosequencing. Serum IGFBP-1 levels were measured with radioimmunoassay. We found that DNA methylation levels in the IGFBP1 gene were decreased (15.6% versus 16.9%; P < 0.001), whereas serum IGFBP-1 levels were increased (31 versus 24 μg/L, P = 0.003) in T1D patients compared with NGT subjects. Furthermore, T1D patients with DN had increased circulating IGFBP-1 concentration compared with the patients without DN (52 versus 28 μg/L; P = 0.006). However, no difference of the IGFBP1 DNA methylation levels between T1D patients with and without DN was observed.
  
  
  CONCLUSIONS
  This study shows for the first time that T1D patients had decreased DNA methylation levels in the IGFBP1 gene and further implies that increased circulating IGFBP-1 levels are associated with T1D and DN.
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Gu
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden ; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Falhammar
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden ; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Harvest F
authors.initials: HF
authors.lastname: Gu
authors.affiliation: Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden ; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
keywords: DNA methylation; Diabetic nephropathy; IGFBP1; Type 1 diabetes