The effect of human proinsulin C-peptide on erythrocyte deformability in patients with Type I diabetes mellitus

Aims/hypothesis. In recent years, evidence has arisen that proinsulin C-peptide exerts biological effects especially on microcirculation, e. g. C-peptide has been shown to increase skin microcirculation in patients with Type I (insulin-dependent) diabetes mellitus and to activate endothelial nitric oxide synthase. This study aimed to investigate the influence of proinsulin C-peptide on erythrocyte deformability which was assessed by means of laser diffractoscopy. Methods. Blood samples from healthy control subjects (n = 10) and Type I diabetic patients (n = 15) completely deficient of C-peptide were analysed at shear stresses ranging from 0.3 to 30 Pa. Results. Erythrocyte deformability was lower in the group of Type I diabetic patients than in the control subjects. Preincubation of the diabetic blood samples with various concentrations of human proinsulin C-peptide for 8 h restored the deformability of erythrocytes, almost reaching the values of control samples. In contrast, proinsulin C-peptide did not modify the erythrocyte deformability of control subjects. Conclusion/interpretation. We conclude that proinsulin C-peptide is able to ameliorate the impaired deformability of erythrocytes in Type I diabetic patients and we hypothesise that this effect is mediated by restoration of Na⁺-K⁺-ATPase activity, which is known to be attenuated in diabetic patients. [Diabetologia (1999) 42: 465–471] Received: 27 August 1998 and in final revised form: 15 December 1998