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Abstract: TH-PO239

The Pro-Fibrotic Molecule Endotrophin as a Risk Marker of Complications in a Type 1 Diabetes Cohort

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical


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

Hyperglycemia can trigger pathological pathways leading to fibrosis where extracellular matrix (ECM) components are accumulated. We investigated the potential of endotrophin (ETP), a molecule generated during collagen type VI (COL6) formation, as a risk marker for complications in an unselected population with type 1 diabetes.


We measured ETP by the PRO-C6 ELISA in serum and urine from 1468 persons with type 1 diabetes recruited between 2012-2016. Urinary values were normalized to urine creatinine levels. Participants were followed for a median of up to 6.4 years. Outcomes were identified through national registers and included a composite renal endpoint (≥40% decline in kidney function or kidney failure), first MACE, all-cause mortality, progression of albuminuria, incident heart failure (HF), incident cardiovascular disease (CVD), and incident sight-threatening eye disease. Cox proportional hazards models adjusted for conventional risk factors were applied. For each outcome, we excluded participants previously diagnosed with the outcome.


The cohort included 712 (49%) females, mean±SD age was 51±16 years, eGFR 94±23 ml/min/1.73m2, and median (IQR) urinary albumin excretion was 5.5 (3.5-11.5) mg/g or g/24h. A doubling of serum ETP was independently associated with the composite renal endpoint, all-cause mortality, and progression of albuminuria, but not with first MACE, incident HF, CVD, or sight-threatening eye disease after adjustment (Table). Urine ETP was not associated with outcomes after adjustment.


Serum ETP was a risk marker for mortality and kidney complications in type 1 diabetes. Biomarkers of ECM remodeling, such as serum ETP, may identify persons with active pro-fibrotic processes at risk for complications related to diabetes.

HR by doubling of serum ETP (95% CI)
 UnadjustedP valueAdjustedP value
Renal endpoint (n=30/1462)4.83 (3.46-6.75)<0.0013.39 (1.98-5.82)<0.001
First MACE (n=82/1316)1.91 (1.48-2.48)<0.0011.28 (0.90-1.80)0.2
All-cause mortality (n=93/1468)2.13 (1.69-2.68)<0.0011.44 (1.03-2.0)0.032
Progression of albuminuria (n=80/1359)1.72 (1.28-2.32)<0.0011.82 (1.32-2.52)<0.001
Incident HF (n=23/1420)2.11 (1.32-1.37)0.0020.76 (0.37-1.56)0.4
Incident CVD (n=68/1215)2.0 (1.52-2.64)<0.0011.43 (1.0-2.05)0.052
Incident sight-threatening eye disease (n=52/1168)0.93 (0.60-1.45)0.70.98 (0.60-1.61)>0.9