Inverse associations between serum levels of secreted frizzled-related protein-5 (SFRP5) and multiple cardiometabolic risk factors: KORA F4 study

Cardiovascular Diabetology

Original Investigation

Wolfgang Koenig¹  Wolfgang Rathmann²  Annette Peters³  Barbara Thorand³  Cornelia Huth³  Christa Meisinger⁴  Maren Carstensen-Kirberg⁵  Julia M. Kannenberg⁵  Christian Herder⁵  Michael Roden⁶  Margit Heier⁷ 

[1] Deutsches Herzzentrum München, Technische Universität München, Munich, Germany;German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany;German Center for Diabetes Research (DZD), München-Neuherberg, Germany;Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany;German Center for Diabetes Research (DZD), München-Neuherberg, Germany;Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;German Center for Diabetes Research (DZD), München-Neuherberg, Germany;Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;Ludwig-Maximilians-Universität München, UNIKA-T Augsburg, Augsburg, Germany;Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf’m Hennekamp 65, 40225, Düsseldorf, Germany;German Center for Diabetes Research (DZD), München-Neuherberg, Germany;Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf’m Hennekamp 65, 40225, Düsseldorf, Germany;German Center for Diabetes Research (DZD), München-Neuherberg, Germany;Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany;Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany;

关键词: Inflammation;    Secreted frizzled-related protein-5;    Cytokine;    Type 2 diabetes;    Cardiometabolic risk;   

DOI  :  10.1186/s12933-017-0591-x

 received in 2017-07-06, accepted in 2017-08-20,  发布年份 2017

来源: Springer

【 摘 要 】

AimsSecreted frizzled-related protein (Sfrp)5 has beneficial effects on insulin sensitivity, inflammation and cardiovascular risk in different mouse models, but its relevance for cardiometabolic diseases in humans is controversial. We aimed to characterise associations of circulating SFRP5 with cardiometabolic risk factors and prediabetes/type 2 diabetes in a large population-based cohort.MethodsCross-sectional associations between serum SFRP5 and cardiometabolic risk factors as well as prediabetes/type 2 diabetes were investigated in 1096 participants aged 62–81 years from the German KORA F4 study, of whom 666 had prediabetes or type 2 diabetes. Multivariable linear regression models were adjusted for potential confounders including age, sex, body mass index (BMI), lifestyle factors, lipids, hypertension, kidney function and myocardial infarction.ResultsHigher serum SFRP5 levels were associated with lower HbA1c, BMI, systolic blood pressure, estimated glomerular filtration rate and high-sensitivity C-reactive protein levels and with higher levels of high-density lipoprotein cholesterol and adiponectin in the fully adjusted model (all P < 0.009). In contrast, favourable associations between SFRP5 and glycaemia, insulin, insulin resistance and other cardiometabolic risk factors were attenuated after adjustment for BMI. Serum SFRP5 levels were lower in participants with prediabetes or type 2 diabetes [(median (25th; 75th percentile) 48.8 (35.5; 65.7) ng/ml] compared to participants with normal glucose tolerance [55.9 (42.6; 69.6) ng/ml] (P < 0.001). In the fully adjusted model, higher SFRP5 was associated with lower odds of prediabetes/type 2 diabetes [OR (95% CI) (0.72 (0.58; 0.89)) per doubling of SFRP5, P < 0.01].ConclusionsHigher serum SFRP5 was inversely associated with multiple risk factors for type 2 diabetes and cardiovascular diseases. However, BMI represents a strong confounder of some of these associations. Higher circulating SFRP5 was also associated with lower odds of prediabetes/type 2 diabetes, and this association was independent of BMI. Thus, SFRP5 emerges as novel biomarker that merits further research in the context of prevention of cardiometabolic diseases.

【 授权许可】

CC BY   
© The Author(s) 2017