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Insulin-like growth factor binding protein 2 (IGFBP-2) and the risk of developing type 2 diabetes

Item Type:Article
Title:Insulin-like growth factor binding protein 2 (IGFBP-2) and the risk of developing type 2 diabetes
Creators Name:Wittenbecher, C. and Ouni, M. and Kuxhaus, O. and Jähnert, M. and Gottmann, P. and Teichmann, A. and Meidtner, K. and Kriebel, J. and Grallert, H. and Pischon, T. and Boeing, H. and Schulze, M.B. and Schürmann, A.
Abstract:Recent studies suggest that insulin-like growth factor binding protein-2 (IGFBP-2) may protect against type 2 diabetes but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk. Within the EPIC-Potsdam cohort (n=27,548), circulating IGFBP-2 concentration was assessed in a nested case-cohort (random subcohort, n=2500, all incident type 2 diabetes cases, n=820). A nested 1:1 matched case-control sample (300 incident type 2 diabetes cases, 300 controls) was constructed for DNA-methylation profiling. Longitudinal associations were evaluated in Cox models (case-cohort) and conditional logistic models (case-control), adjusting for age, sex, anthropometry, lifestyle and a large set of type 2 diabetes-related biomarkers. Higher circulating IGFBP-2 concentrations (median 92 ng/mL) were cross-sectional linked to lower BMI, waist circumference, fatty liver index, triglycerides, fetuin A, ALT and γ-GT, and longitudinal associated with lower type 2 diabetes risk (HR per SD 0.65, 95%CI 0.53, 0.8). A methylation score based on seven type 2 diabetes-related CpGs in the IGFBP-2 gene was associated with higher type 2 diabetes risk (OR per SD 2.7, 95%CI 2.1, 3.5). Our results are consistent with a type 2 diabetes-protective effect of high circulating IGFBP-2 concentration, and suggest that epigenetic silencing of the IGFBP-2 gene might predispose for type 2 diabetes.
Keywords:Blood Glucose, DNA Methylation, Diabetes Mellitus Type 2, Insulin-Like Growth Factor Binding Protein 2, Phenotype, Prospective Studies
Publisher:American Diabetes Association
Page Range:188-197
Date:1 January 2019
Official Publication:https://doi.org/10.2337/db18-0620
PubMed:View item in PubMed

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