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Abstract: PO0734

The Extracellular Matrix Signaling Molecule Endotrophin Is Associated with Diabetic Complications in Type 1 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Møller, Alexandra L., Nordic Bioscience, Herlev, Denmark
  • Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Herlev , Denmark
  • Tougaard, Ninna Hahn, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Rønn, Pernille Falberg, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Genovese, Federica, Nordic Bioscience, Herlev, Herlev , Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Herlev , Denmark
  • Hansen, Tine, Steno Diabetes Center Copenhagen, Gentofte, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Gentofte, Denmark
Background

Persons with diabetes have a high risk of late complications related to both the micro- and macrovascular circulation. Early intervention targeting several risk factors is implemented, but tools to predict complications before clinical manifestations are still lacking. The PRO-C6 assay reflects collagen (COL) type VI formation and levels of endotrophin (ETP), a bioactive molecule derived from COL VI. In this study, we investigated the cross-sectional association between ETP and microvascular complications. Follow-up data is currently being collected to investigate the potential of ETP to predict development of complications and mortality.

Methods

We measured ETP in 1444 serum (S-ETP) and 1249 urine (U-ETP) samples (collected from 2012 to 2016), using the PRO-C6 ELISA (Nordic Bioscience) in persons with type 1 diabetes recruited from Steno Diabetes Center Copenhagen. All urine samples were normalized to urinary creatinine levels.

Results

In crude analyses, S-ETP levels increased significantly with CKD stage and albuminuria stage, and presence of retinopathy and neuropathy (all P<0.0001). S-ETP could discriminate patients with eGFR < 60 ml/min/1.73 m2 with an AUC of 0.83 (P<0.001). In multiple linear regression analyses including age, sex, SBP, smoking, BMI, LDL cholesterol, HbA1c, albumin excretion and eGFR, lower age (r=-0.16, P<0.0001), higher albumin excretion (r=0.35, P<0.0001) and lower eGFR (r=-0.30, P<0.0001) were associated with higher S-ETP levels. U-ETP levels were not associated with disease severity or any of the investigated parameters. Following multiple linear regression, none of the parameters were associated with U-ETP. There was no correlation between S-ETP and U-ETP.

Conclusion

In conclusion, we demonstrate that ETP released during COL VI formation was associated with kidney disease severity, retinopathy, and neuropathy in patients with type 1 diabetes. These findings may indicate that ETP identifies diabetic patients with active fibrogenesis, and tissue injury. The potential of ETP to predict complications and mortality will be investigated once follow-up data has been collected.