title: In vivo monitoring of serum protein cross linking in patients with diabetes mellitus. Evidence for pharmacological modification of immunoglobulin G cross links.
abstract: It is well known that increased cross linking of proteins due to nonenzymatic glycosylation occurs in diabetic animals and humans leading to accumulation of proteins (e.g. collagen). This in turn is strongly associated with diabetic long term complications.We developed a noninvasive method for studying in vivo cross linking and its pharmacological inhibition by L-arginine in a blind placebo controlled study with crossing over of two treatment periods of three months each.Glycemic control was assessed by determining blood glucose, HbA1c, fructosamine, and total glycosylated hemoglobin. The patients were randomly assigned to two treatment groups A (n = 14) and B (n = 16). 20 healthy volunteers served as controls. Treatment consisted of two daily dosages of 1 g L-arginine free base. Cross linking of a human serum protein (IgG) was assessed by SDS polyacrylamide gel electrophoresis and subsequent Western blotting.Diabetic patients showed a statistically increased number of cross links compared to normal controls (Group A: 3.6 vs 2.0 bands, group B: 3.8 vs 2.0 bands). L-arginine led to a significant reduction of cross links in both treatment groups (Group A: 3.6 to 2.1 bands, group B: 3.8 to 2.5 bands).The described noninvasive method for assessing in vivo cross linking requires onlyµl amounts of serum and could serve to monitor protein cross linking in patients with diabetes mellitus.
authors.affiliation: FRSC, Department of Pediatrics, University of Vienna, Waehringer Guertel 18-20, A-1090, Wien, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Lubec
authors.forename: M
authors.initials: M
authors.lastname: Weninger
authors.forename: C
authors.initials: C
authors.lastname: Popow
authors.forename: H
authors.initials: H
authors.lastname: Vierhapper
authors.forename: J
authors.initials: J
authors.lastname: Lunec
authors.forename: G
authors.initials: G
authors.lastname: Lubec