Abstract: TH-PO239
The Pro-Fibrotic Molecule Endotrophin as a Risk Marker of Complications in a Type 1 Diabetes Cohort
Session Information
- Diabetic Kidney Disease: Clinical - I
November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
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)
| Unadjusted | P value | Adjusted | P value | |
| Renal endpoint (n=30/1462) | 4.83 (3.46-6.75) | <0.001 | 3.39 (1.98-5.82) | <0.001 |
| First MACE (n=82/1316) | 1.91 (1.48-2.48) | <0.001 | 1.28 (0.90-1.80) | 0.2 |
| All-cause mortality (n=93/1468) | 2.13 (1.69-2.68) | <0.001 | 1.44 (1.03-2.0) | 0.032 |
| Progression of albuminuria (n=80/1359) | 1.72 (1.28-2.32) | <0.001 | 1.82 (1.32-2.52) | <0.001 |
| Incident HF (n=23/1420) | 2.11 (1.32-1.37) | 0.002 | 0.76 (0.37-1.56) | 0.4 |
| Incident CVD (n=68/1215) | 2.0 (1.52-2.64) | <0.001 | 1.43 (1.0-2.05) | 0.052 |
| Incident sight-threatening eye disease (n=52/1168) | 0.93 (0.60-1.45) | 0.7 | 0.98 (0.60-1.61) | >0.9 |