1438-P: The Novel Extracellular Matrix Hormone Endotrophin, a Fragment of Collagen Type VI, Is Associated with Diabetes and Is a Risk Factor for Mortality in Elderly Women

Abstract

As a result of the aging population and obesity, diabetes is a major, increasing public health issue approaching global epidemic proportions. It is well known that patients with diabetes have higher levels of inflammation and that the underlying pathology contributes to blood vessel damage resulting in cardiovascular complications. Recently it was suggested that a fragment of collagen type VI (COL VI), released during deposition, is in fact a novel hormone (endotrophin; ETP), suggesting the extracellular matrix (ECM) to be involved in the regulation of type 2 diabetes. In this study, we investigated the association of ETP (measured by the PRO-C6 ELISA) with diabetes and mortality in a large prospective cohort. From 1999-2001, 5855 postmenopausal women with a mean±SD age of 71±6.5 were included in the Prospective Epidemiological Risk Factor study, and visits were planned according to a pre-defined protocol. The diagnoses for diabetes and mortality were extracted from the Danish Health Registries. We measured ETP in serum of 5608 women at baseline (samples collected from 1999-2001). ETP levels were measured in 2016. ETP levels were significantly elevated in women who died (p<0.0001). Additionally, we found that ETP levels were higher in women diagnosed with diabetes prior to baseline visit (n=206) compared to women diagnosed with diabetes after baseline (n=515, p=0.017), that ETP were higher in women with diabetes prior to baseline compared to healthy women (p<0.0001), and a trend of higher levels of ETP in women diagnosed with diabetes after baseline compared to healthy women (p=0.10). In conclusion, we demonstrate that the hormone ETP, a biomarker also reflecting COL VI deposition, was increased in serum of postmenopausal women with diabetes compared to healthy women. In addition, we show that ETP was associated with mortality, suggesting that turnover of the ECM is very important in metabolic disorders. Disclosure A. Møller: None. D.G.K. Rasmussen: Employee; Self; Nordic Bioscience. M.A. Karsdal: Stock/Shareholder; Self; Nordic Bioscience. C. Christiansen: None. L.M. Staunstrup: None. C.L. Bager: None. Funding Danish Research Foundation