Extracellular matrix proteins as risk markers for complications in type 1 diabetes

Aims Kidney fibrosis, characterised by impaired extracellular matrix remodelling and excessive collagen deposition, is a hallmark of chronic kidney disease in diabetes. We investigated whether biomarkers reflecting collagen formation and degradation were associated with complications in type 1 diabetes. Methods In this observational cohort study, markers of collagen type III (PRO‐C3), VII (PRO‐C7) and XXVIII (PRO‐C28) formation and collagen type III degradation (CTX‐III) were measured in serum by ELISA. Associations between baseline biomarker levels and a composite kidney endpoint, all‐cause mortality, albuminuria progression and cardiovascular events were tested using Cox proportional hazards models adjusted for traditional risk factors. Hazard ratios (HRs) are reported per 1‐SD increase in log 2 ‐transformed biomarker levels. Results Over a median follow‐up of 6.3 (IQR: 5.9–6.7) years, 125 of 662 participants experienced the composite kidney endpoint, 58 participants died, 102 progressed in albuminuria and 94 developed a cardiovascular event. Higher baseline levels of PRO‐C3 were associated with the development of the composite kidney endpoint (adjusted HR: 1.30, 95% CI 1.08–1.57, p < 0.01) and mortality (adjusted HR: 1.36, 95% CI 1.06–1.76, p = 0.016). No associations were found between PRO‐C3 and albuminuria progression or cardiovascular events. PRO‐C7, PRO‐C28 and CTX‐III were not associated with any of the endpoints. Conclusions Higher baseline serum PRO‐C3, a marker of collagen type III formation and fibrogenesis, was associated with an increased risk of developing the composite kidney endpoint and all‐cause mortality in individuals with type 1 diabetes.