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Endothelial and neural regulation of skin microvascular blood flow in patients with diabetic peripheral neuropathy: effect of treatment with the isoform-specific protein kinase C beta inhibitor, ruboxistaurin.
J Diabetes Complications 2008 Mar-Apr; 22(2):88-95JD

Abstract

PURPOSE

This article aims to study the effects of ruboxistaurin (RBX) on skin microvascular blood flow (SkBF) and evaluate the relationship between endothelial and neural control of SkBF in patients with diabetic peripheral neuropathy (DPN).

METHODS

We studied 11 placebo- and 9 RBX (32 mg/day)-treated patients who participated in a 1-year, double-masked, randomized, Phase 3 study of RBX for treatment of DPN sensory symptoms. Patients had type 1 or type 2 diabetes, a detectable sural sensory nerve action potential, and Neuropathy Total Symptom Score-6 (NTSS-6) >6 points. SkBF was measured by laser Doppler velocimetry, combined with iontophoresis of acetylcholine and sodium nitroprusside, at baseline, 3 months, and 1 year. Sensory symptoms and electrophysiology were also evaluated during the study. The relationship between endothelial and neural control of SkBF at baseline was assessed using linear regression.

RESULTS

No significant differences (RBX vs. placebo) were demonstrable for post-iontophoresis SkBF [fold increase from basal state (1 year): endothelium-dependent, 3.6 vs. 8.6; endothelium-independent, 3.7 vs. 2.0; C fiber-mediated, 1.7 vs. 2.0; P>.05] or sensory symptoms [NTSS-6 total score (1 year): 7.7 vs. 6.0 points; P=.4]. There were also no significant between-group differences in nerve conduction parameters, except for placebo peroneal nerve conduction velocity, which demonstrated a statistically significant improvement of unknown clinical importance (Z=2.1; P=.034). At baseline, C fiber-mediated vasodilatation correlated well with endothelium-dependent vasodilation (r=.7, P<.01) but not with endothelium-independent vasodilatation (r=-.1, P=.7).

CONCLUSIONS

RBX demonstrated no effect on SkBF or sensory symptoms after 1 year in this cohort. The correlation between C fiber-mediated and endothelium-dependent SkBF at baseline suggests that improving endothelial function could affect the microcirculation not only locally but also via the neurovascular arcade.

Authors+Show Affiliations

Diabetes Centre, Royal Prince Alfred Hospital, and Discipline of Medicine, The University of Sydney, Sydney, New South Wales, Australia. belinda@email.cs.nsw.gov.auNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18280438

Citation

Brooks, Belinda, et al. "Endothelial and Neural Regulation of Skin Microvascular Blood Flow in Patients With Diabetic Peripheral Neuropathy: Effect of Treatment With the Isoform-specific Protein Kinase C Beta Inhibitor, Ruboxistaurin." Journal of Diabetes and Its Complications, vol. 22, no. 2, 2008, pp. 88-95.
Brooks B, Delaney-Robinson C, Molyneaux L, et al. Endothelial and neural regulation of skin microvascular blood flow in patients with diabetic peripheral neuropathy: effect of treatment with the isoform-specific protein kinase C beta inhibitor, ruboxistaurin. J Diabetes Complicat. 2008;22(2):88-95.
Brooks, B., Delaney-Robinson, C., Molyneaux, L., & Yue, D. K. (2008). Endothelial and neural regulation of skin microvascular blood flow in patients with diabetic peripheral neuropathy: effect of treatment with the isoform-specific protein kinase C beta inhibitor, ruboxistaurin. Journal of Diabetes and Its Complications, 22(2), pp. 88-95. doi:10.1016/j.jdiacomp.2007.07.002.
Brooks B, et al. Endothelial and Neural Regulation of Skin Microvascular Blood Flow in Patients With Diabetic Peripheral Neuropathy: Effect of Treatment With the Isoform-specific Protein Kinase C Beta Inhibitor, Ruboxistaurin. J Diabetes Complicat. 2008;22(2):88-95. PubMed PMID: 18280438.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelial and neural regulation of skin microvascular blood flow in patients with diabetic peripheral neuropathy: effect of treatment with the isoform-specific protein kinase C beta inhibitor, ruboxistaurin. AU - Brooks,Belinda, AU - Delaney-Robinson,Carol, AU - Molyneaux,Lynda, AU - Yue,Dennis K, PY - 2006/07/31/received PY - 2007/05/09/revised PY - 2007/07/10/accepted PY - 2008/2/19/pubmed PY - 2008/5/21/medline PY - 2008/2/19/entrez SP - 88 EP - 95 JF - Journal of diabetes and its complications JO - J. Diabetes Complicat. VL - 22 IS - 2 N2 - PURPOSE: This article aims to study the effects of ruboxistaurin (RBX) on skin microvascular blood flow (SkBF) and evaluate the relationship between endothelial and neural control of SkBF in patients with diabetic peripheral neuropathy (DPN). METHODS: We studied 11 placebo- and 9 RBX (32 mg/day)-treated patients who participated in a 1-year, double-masked, randomized, Phase 3 study of RBX for treatment of DPN sensory symptoms. Patients had type 1 or type 2 diabetes, a detectable sural sensory nerve action potential, and Neuropathy Total Symptom Score-6 (NTSS-6) >6 points. SkBF was measured by laser Doppler velocimetry, combined with iontophoresis of acetylcholine and sodium nitroprusside, at baseline, 3 months, and 1 year. Sensory symptoms and electrophysiology were also evaluated during the study. The relationship between endothelial and neural control of SkBF at baseline was assessed using linear regression. RESULTS: No significant differences (RBX vs. placebo) were demonstrable for post-iontophoresis SkBF [fold increase from basal state (1 year): endothelium-dependent, 3.6 vs. 8.6; endothelium-independent, 3.7 vs. 2.0; C fiber-mediated, 1.7 vs. 2.0; P>.05] or sensory symptoms [NTSS-6 total score (1 year): 7.7 vs. 6.0 points; P=.4]. There were also no significant between-group differences in nerve conduction parameters, except for placebo peroneal nerve conduction velocity, which demonstrated a statistically significant improvement of unknown clinical importance (Z=2.1; P=.034). At baseline, C fiber-mediated vasodilatation correlated well with endothelium-dependent vasodilation (r=.7, P<.01) but not with endothelium-independent vasodilatation (r=-.1, P=.7). CONCLUSIONS: RBX demonstrated no effect on SkBF or sensory symptoms after 1 year in this cohort. The correlation between C fiber-mediated and endothelium-dependent SkBF at baseline suggests that improving endothelial function could affect the microcirculation not only locally but also via the neurovascular arcade. SN - 1056-8727 UR - https://www.unboundmedicine.com/medline/citation/18280438/Endothelial_and_neural_regulation_of_skin_microvascular_blood_flow_in_patients_with_diabetic_peripheral_neuropathy:_effect_of_treatment_with_the_isoform_specific_protein_kinase_C_beta_inhibitor_ruboxistaurin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1056-8727(07)00091-8 DB - PRIME DP - Unbound Medicine ER -