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Abstract: TH-PO172

Evaluation of Extracellular Matrix Turnover Proteins as Risk Markers in Persons with Type 2 Diabetes and Microalbuminuria

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Wasehuus, Victor, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Skriver-Møller, Anne-Cathrine, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Møller, Alexandra L., Nordic Bioscience, Herlev, Denmark
  • Rasmussen, Daniel Guldager Kring, Nordic Bioscience, Herlev, Denmark
  • Genovese, Federica, Nordic Bioscience, Herlev, Denmark
  • Reinhard, Henrik, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Von Scholten, Bernt Johan, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Jacobsen, Peter Karl, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Parving, Hans-Henrik, Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
  • Karsdal, Morten Asser, Nordic Bioscience, Herlev, Denmark
  • Hansen, Tine, Steno Diabetes Center Copenhagen, Herlev, Capital Region, Denmark
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, Denmark
Background

Increased turnover of extracellular matrix (ECM) proteins has been demonstrated in many diseases and is an underlying and driving feature of pathogenesis. We investigated whether biomarkers of ECM turnover were risk markers for occurrence of cardiovascular disease (CVD), mortality and progression of chronic kidney disease (CKD) in persons with type 2 diabetes (T2D) and microalbuminuria. Altered levels of the biomarkers were hypothesized to be detrimental.

Methods

Serum concentration of TUM (tumstatin, a matrikine of collagen type IV), TGF-β (a pro-fibrotic cytokine), C1M (a degradation product of collagen type I), CTX-III (a degradation product of cross-linked collagen type III), PRO-C7 (a pro-peptide of collagen type VII) and PRO-C28 (a C-terminal of collagen type XXVIII) was measured in 192 participants with T2D and microalbuminuria included in an observational, prospective study at Steno Diabetes Center Copenhagen in Denmark from 2007-2008. Endpoints were CVD, mortality and CKD progression (>30% decline in estimated glomerular filtration rate (eGFR)) with mortality as competing risk.

Results

Mean (SD) age was 59 (9) years, eGFR was 89 (17) ml/min/1.73m2, median (IQR) urine albumin excretion rate (UAE) was 102 (39–229) mg/24-h and 75 % were males. Median follow-up ranged from 4.9 to 6.3 years, and 38 CVD events, 24 deaths and 40 CKD events were recorded.
Higher C1M was associated with higher risk of CKD progression in the crude model (hazard ratio (per doubling): 1.62 (95% CI: 1.01-2.61), p=0.047), but not after adjustment for sex, age, body mass index, LDL cholesterol, smoking, HbA1c, plasma creatinine, systolic blood pressure and UAE (p=0.15). None of the other markers were associated with CKD progression (p≥0.20), and none of the markers were associated with mortality (p≥0.11) or CVD (p≥0.19).

Conclusion

In this cohort of individuals with T2D and microalbuminuria, higher level of a degradation product of collagen type I (C1M) was associated with CKD progression, but not independent of other risk factors. None of the extracellular matrix turnover proteins were associated with risk of CVD or mortality.

Funding

  • Private Foundation Support