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

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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., Ouni, M., Kuxhaus, O., Jähnert, M., Gottmann, P., Teichmann, A., Meidtner, K., Kriebel, J., Grallert, H., Pischon, T., Boeing, H., 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
Source:	Diabetes
ISSN:	0012-1797
Publisher:	American Diabetes Association
Volume:	68
Number:	1
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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