Alterations of biochemical and two-dimensional biomechanical properties of human skin in diabetes mellitus as compared to effects of in vitro non-enzymatic glycation.

Objective: The aim of this study was to evaluate whether multiaxial analysis of diabetes-specific biomechanical changes generated in vitro by non-enzymatic glycation of human skin samples from healthy subjects reflect the changes seen in skin from subjects with diabetes mellitus.

Design: Descriptive study.

Background: Non-enzymatic glycation of skin in vitro causes an increased stiffness comparable to in vivo changes seen in diabetic patients. These changes are probably due to increased cross-linking of collagen molecules.

Methods: Skin specimens from 7 subjects with diabetes mellitus and 7 controls (age range: 74-90) were analyzed for biomechanical changes using a multiaxial tensile testing device. Control skins from healthy individuals in the age range of 50-65 yr were artificially glycated. One part of these samples was coincubated with the glycation inhibitor aminoguanidine. Glycation of tissues was determined by measuring fluorescence of solubilized samples. Multiaxial biomechanical analysis allows the determination of maximum (a(I)) and minimum elastic modulus (a(II)). These parameters describe the amplitude of the elastic stress response, which is exponentially related to strain.

Results: Principal stresses, both maximum and minimum, were increased in skins from diabetic subjects as compared to controls. The increases of the principal stresses were comparable to those obtained by in vitro glycation of normal skins.

Conclusion: These results, which can be detected unequivocally with the multiaxial test mode, show that our in vitro model closely reflects changes in skin samples from individuals with diabetes mellitus. Aminoguanidine partially inhibited these as well as biochemical changes.

Relevance: Multiaxial testing of in vitro glycated skin samples can be used as a model for in vivo changes caused by diabetes mellitus. In addition, therapeutical effects of aminoguanidine, an inhibitor of non-enzymatic glycation, can be monitored in this model.