Evaluation of IGFBP-7 DNA methylation changes and serum protein variation in Swedish subjects with and without type 2 diabetes

Clinical Epigenetics

Kerstin Brismar³  Kazuhiro Tamura⁴  Jan Frystyk¹  Masahiko Kutsukake⁴  Maode Lai²  Claes-Göran Östenson³  Lars Kärvestedt³  Yiming Zhu²  Agneta Hilding³  Tianwei Gu³  Harvest F Gu³ 

[1] Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark;Department of Molecular Pathology, School of Medicine, Zhejiang University, Hangzhou, PR China;Rolf Luft Research Center for Diabetes and Endocrinology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm SE-171 76, Sweden;Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan

关键词: Type 2 diabetes;    Insulin;    IGFBP-7;    IGFBP-1;    IGF-1;   

Others  :  790744
DOI  :  10.1186/1868-7083-5-20

 received in 2013-07-04, accepted in 2013-10-05,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Gu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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