Livshits L.,The Diabetes Research Center |
Srulevich A.,The Diabetes Research Center |
Raz I.,The Diabetes Research Center |
Cahn A.,Endocrinology and Metabolism Service |
And 3 more authors.
Review of Diabetic Studies | Year: 2012
BACKGROUND: Diabetes mellitus, characterized by chronic hyperglycemia, is known to have a deleterious effect on erythrocyte structure and hemodynamic characteristics, which eventually contribute to diabetes-associated vascular complications. Protein kinase C alpha (PKCα) is a major regulator of many metabolic processes and structural changes in erythrocytes, and may play a significant role in the development of hyperglycemia-mediated cellular abnormalities. AIM: We hypothesized that acute hyperglycemic stress may affect erythrocyte structure and metabolic properties through its effect on PKCα membrane content and activity. RESULTS: Erythrocytes, from healthy individuals acutely exposed to a glucose enriched media, showed a significant decrease in the membranous fraction of PKCα and its phosphorylation (p = 0.005 and p = 0.0004, respectively). These alterations correlated with decreased affinity of PKCα to its membrane substrates (4.1R and GLUT1) and reduced RBC deformability (p = 0.017). Pre-activation of erythrocytes with PKC activator, PMA, minimized the effect of glucose on the membrane PKCα fraction and RBC deformability (p > 0.05). CONCLUSIONS: Acute glycemiainduced inhibition of PKCα membranous translocation and activation is associated with reduced erythrocyte membrane deformability.
The Rate of Decline in Small Fibre Function Assessed Using Axon Reflex-Mediated Neurogenic Vasodilatation and the Importance of Age Related Centile Values to Improve the Detection of Clinical Neuropathy
Vas P.R.J.,The Diabetes Research Center |
Rayman G.,The Diabetes Research Center
PLoS ONE | Year: 2013
Background: The LDIflare technique (LDIflare) is a simple non-invasive test of small fibre function in dorsal foot skin involving skin heating and measuring the size of the resulting axon reflex-mediated vasodilator (flare) response using a laser Doppler imager (LDI). This study establishes age-related normative reference ranges for the test and determines the rate of decline in small fibre function per decade. Additionally, the potential value of using age related centiles rather than Receiver Operator Curves (ROC) was explored by comparison of the sensitivity and specificity of each analytic technique in identifying clinical neuropathy. Methods: LDIflare areas were assessed in 94 healthy controls and 66 individuals with diabetes with (DN+, n = 31) and without clinical neuropathy (DN-, n = 35); neuropathy defined as a Neuropathy Disability Score ≥3. The age specific 5th centile values were used as the 'cut-offs' for the diagnosis of neuropathy from which sensitivity and specificity were calculated. Results: There was a significant age dependant decrease in LDIflare size (r = -0.42, p<0.0001) with no significant gender differences. The LDIflare size reduced 0.56 cm2 per decade which gives a percentage reduction of approximately 5.5% per decade. Using the normative 5th centiles as the cut-offs, the technique had a sensitivity of 77%, specificity of 90%, positive predictive value of 82% and negative predictive value of 87%.The ROC analysis gave a threshold of <3.66 cm2 for the cut-off, resulting in a sensitivity of 75%, specificity of 85%, positive predictive value of 74% and negative predictive value of 86%. Conclusions: There is an age dependent decrease in small fibre function in the foot of 5.5% per decade. Both analytic techniques demonstrate good sensitivity and specificity for detecting clinical neuropathy but the technique based on age centiles offers better diagnostic accuracy and is therefore proposed as the method of choice. © 2013 Vas, Rayman.