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Decrease of Collagen Deposition in Wound Repair in Type 1 Diabetes Independent of Glycemic Control
Eva Black, MD;
Jette Vibe-Petersen, MD;
Lars N. Jorgensen, MD;
Søren M. Madsen, PhD;
Magn s S. Ågren, DMSc;
Per E. Holstein, MD, DMSc;
Hans Perrild, MD;
Finn Gottrup, MD, DMSc
Arch Surg. 2003;138:34-40.
Hypothesis Type 1 and type 2 diabetes mellitus and glycemic control influence wound healing in humans.
Design Experimental study using a human wound-healing model.
Setting Collaboration among a multidisciplinary wound-healing department, department of medicine, and research laboratories.
Patients, Control Subjects, and Methods In 34 patients with type 1 (insulin-dependent) and 25 with type 2 (non–insulin-dependent) diabetes and 5 nondiabetic control subjects matched with the type 2 diabetic patients, wound-healing capacity was determined as subcutaneous accumulation of collagen measured as hydroxyproline. Two expanded polytetrafluoroethylene tubes were implanted and removed 10 days later. The hydroxyproline level was determined by means of high-performance liquid chromatography; the collagenase activity, by using a radiolabeled collagen substrate. Proliferation of fibroblasts cultured from the wounds was studied in patient groups.
Results The deposition of hydroxyproline decreased by 40% (P = .03) in type 1 compared with type 2 diabetes (median, 0.70 vs 1.16 nmol/mg; interquartile range, 0.48-1.04 vs 0.56-1.63 nmol/mg), which in turn did not differ significantly from that of controls (median, 1.35 nmol/mg; interquartile range, 0.72-1.88 nmol/mg). The decreased collagen deposition in type 1 diabetes was not caused by increased collagenase activity. The deposition of hydroxyproline did not correlate significantly (rs = 0.07; P = .63) with glycosylated hemoglobin levels in either diabetic group. Fibroblast growth was also decreased in type 1 compared with type 2 diabetic patients and controls.
Conclusions Collagen deposition in acute wounds is impaired in type 1 diabetes, possibly due to a decreased fibroblast proliferation. In type 2 diabetes, collagen deposition is normal. Glycemic control does not influence collagen deposition in acute wound repair in type 1 or in type 2 diabetes mellitus.
From the Copenhagen Wound Healing Center (Drs Black, Jorgensen, Holstein, and Gottrup) and the Medical Department I, Bispebjerg Hospital, University of Copenhagen (Drs Vibe-Petersen and Perrild), Copenhagen, Denmark; and Coloplast Research (Dr Madsen) and Aagren Dermaconsulting ApS (Dr Ågren), Humlebæk, Denmark.
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