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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

Authors

  • 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
Background

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.

Methods

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.

Results

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.

Conclusion

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