Diabetologie und Stoffwechsel 2019; 14(S 01): S43
DOI: 10.1055/s-0039-1688231
Poster
Entzündung und mehr
Georg Thieme Verlag KG Stuttgart · New York

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

M Ouni
1   Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE), Experimentalle Diabetologie, Potsdam, Germany
,
C Wittenbecher
2   German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Department of Molecular Epidemiology, Potsdam, Germany
,
O Kuxhaus
2   German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Department of Molecular Epidemiology, Potsdam, Germany
,
M Jaehnert
2   German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Department of Molecular Epidemiology, Potsdam, Germany
,
M Schulze
2   German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Department of Molecular Epidemiology, Potsdam, Germany
,
A Schürmann
2   German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Department of Molecular Epidemiology, Potsdam, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
07 May 2019 (online)

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Background:

Recent studies suggest that insulin-like growth factor binding protein-2 (IGFBP-2) may protect against type 2 diabetes but population based studies are not available. 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.

Methods:

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.

Results:

Higher circulating IGFBP-2 concentrations (median 92 ng/mL) were cross-sectionally linked to lower BMI, waist circumference, fatty liver index, triglycerides, fetuin A, ALT and γ-GT, and longitudinally 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).

Conclusions:

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.