BACKGROUND: QR-333, a topical compound that contains quercetin, a flavonoid with aldose reductase inhibitor effects, ascorbyl palmitate, and vitamin D(3), was formulated to decrease the oxidative stress that contributes to peripheral diabetic neuropathy and thus alleviate its symptoms. This proof-of-principle study assessed the efficacy and safety of QR-333 against placebo in a small cohort of patients with diabetic neuropathy. METHODS: This randomized, placebo-controlled, double-blind trial included 34 men and women (21-71 years of age) with Type 1 or 2 diabetes and diabetic neuropathy who applied QR-333 or placebo (2:1 ratio), three times daily for 4 weeks, to each foot where symptoms were experienced. Five-point scales were used to determine changes from baseline to endpoint in symptoms and quality of life (efficacy). Safety was assessed through concomitant medications, adverse events, laboratory evaluations, and physical examinations. RESULTS: QR-333 reduced the severity of numbness, jolting pain, and irritation from baseline values. Improvements were also seen in overall and specific quality-of-life measures. QR-333 was well tolerated. Eleven patients in the QR-333 group reported 23 adverse events (all mild or moderate); 4 in the placebo group reported 5 events (all moderate). One patient who applied QR-333 noted a pricking sensation twice, the only adverse event considered possibly related to study treatment. CONCLUSIONS: From this preliminary safety study, it appears that QR-333 may safely offer relief of symptoms of diabetic neuropathy and improve quality of life. These findings warrant further investigation of this topical compound.

OBJECTIVES: The objectives of this study were to investigate the effects of acupressure therapy (AT) on the development and progression of diabetic complications in Chinese patients with type 2 diabetes (T2D). DESIGN AND METHODS: A total of 80 patients with T2D were recruited for a randomized clinical study of the effect of AT on the progression and development of diabetic complications, and 64 patients were followed up for 3 years. All patients with T2D were treated with regular medicines and participated in diet and exercise programs for the control of hyperglycemia and hypertension. The patients in the AT group received additional treatment of a 90-minute AT 4-6 times per week for 3 consecutive years. Their blood lipids, fasting glucose levels, and heart and kidney functions and nerve conduction velocity (NCV) were longitudinally monitored before and every 12 months after AT. RESULTS: Following AT therapy for 3 years, significantly lower levels of total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and higher levels of high-density lipoprotein-cholesterol (HDL-C) were observed and no significantly increased levels of serum creatinine and urine protein were detected in the AT group, as compared with that in controls. Furthermore, the mean values of NCV in the AT group at 2 years post-treatment were significantly greater than those of controls and were further elevated at the end of this study. Therefore, AT inhibited the progression of hyperlipidemia and improved diabetes-associated kidney function and neuropathy in Chinese patients with T2D. CONCLUSIONS: AT may be an effective nonpharmacological adjunctive strategy for alleviating the development and progression of T2D-related complications.

OBJECTIVE: To observe therapeutic effect of acupuncture on peripheral diabetic neuropathies in the African area. METHODS: Five Shiu points on the four limbs were selected. Jing (well-point) was needled by pricking method for blood letting, and acupuncture was given at points Xing (spring-point), Shu (stream-point), Jing (river-point) and He (sea-point), and after arrival of qi, the needles were retained for 30 min, once every other day, for 2 therapeutic courses. RESULTS: Forty-five cases were markedly effective and 68 cases were effective, the total effective rate being 89.68%. CONCLUSION: Acupuncture has obvious therapeutic effect on diabetic neuropathies in the African area.

OBJECTIVE: To observe therapeutic effect of acupuncture on peripheral diabetic neuropathies in the African area. METHODS: Five Shiu points on the four limbs were selected. Jing (well-point) was needled by pricking method for blood letting, and acupuncture was given at points Xing (spring-point), Shu (stream-point), Jing (river-point) and He (sea-point), and after arrival of qi, the needles were retained for 30 min, once every other day, for 2 therapeutic courses. RESULTS: Forty-five cases were markedly effective and 68 cases were effective, the total effective rate being 89.68%. CONCLUSION: Acupuncture has obvious therapeutic effect on diabetic neuropathies in the African area.

Biotin in high doses was given for 1-2 years to three diabetic patients suffering from severe diabetic peripheral neuropathy. Within 4-8 weeks there was a marked improvement in clinical and laboratory findings. It is suggested that in diabetes may exist a deficiency, inactivity or unavailability of Biotin, resulting in disordered activity of biotin-dependent enzyme, pyruvate carboxylase, leading to accumulation of pyruvate and/or depletion of aspartate, both of which play a significant role in nervous system metabolism. Based on our good results, regular biotin administration could be suggested for every diabetic patient for the prevention and management of peripheral neuropathy although extensive randomised clinical trials are required

Background. The restricted usage of existing pharmacological methods which do not seem to provide the treatment of diabetic neuropathy may lead to exploring the efficacy of a complementary therapy. In this context, this paper was devoted to evaluate the efficacy of foot reflexology. This health science works on the hypothesis that the dysfunctional states of body parts could be identified by observing certain skin features and be rectified by stimulating certain specific areas mapped on feet. Method. Subjects (N = 58) with diagnosed diabetic neuropathy were randomly distributed into reflexology and control groups in which both group patients were treated with ongoing pharmacological drugs. Reflexology group patients were additionally treated holistically with the hypothesis that this therapy would bring homeostasis among body organ functions. This was a caregiver-based study with a follow-up period of 6 months. The outcome measures were pain reduction, glycemic control, nerve conductivity, and thermal and vibration sensitivities. The skin features leading to the detection of the abnormal functional states of body parts were also recorded and analyzed. Results. Reflexology group showed more improvements in all outcome measures than those of control subjects with statistical significance. Conclusion. This study exhibited the efficient utility of reflexology therapy integrated with conventional medicines in managing diabetic neuropathy.

AIMS: To evaluate the effectiveness of transcutaneous electrical nerve stimulation (TENS) on diabetic peripheral neuropathy (DPN). METHODS: Randomized controlled trials (RCTs) comparing TENS with routine care, pharmacological interventions or placebo devices on patients with symptomatic DPN, were identified by electronic and manual searches. Studies were selected and available data were extracted independently by two investigators. Meta-analysis was performed by RevMan 4.2.8 software. RESULTS: Three RCTs involving 78 patients were included in this study. The reductions in mean pain score were significantly greater in TENS group than in placebo TENS group in 4 weeks and 6 weeks follow-up [4 weeks, SMD-5.37, 95% CI (-6.97, -3.77); 6 weeks, SMD-1.01, 95% CI (-2.01, -0.01)], but not in 12 weeks follow-up [SMD-1.65, 95% CI (-4.02, 0.73)]. TENS therapy was associated with significantly subjective improvement in overall neuropathic symptoms in 12 weeks follow-up [WMD-0.18, 95% CI (-0.32, -0.051)]. No TENS-related adverse events were registered in TENS group. CONCLUSIONS: TENS therapy may be an effective and safe strategy in treatment of symptomatic DPN. Due to small sample and short-term treatment duration, large multi-centre RCTs are needed to further evaluate the long-term effect of TENS on DPN.

Reactive oxygen species (ROS) are elevated by metabolic changes in diabetes, including autoxidation and increased advanced glycation. Endogenous protection by the glutathione redox cycle is also compromised by the competing NADPH requirement of elevated polyol pathway flux. Antioxidant treatment strategies prevent or reverse nerve conduction velocity (NCV) deficits in diabetic rats. These include lipophilic scavengers such as butylated hydroxytoluene, probucol and vitamin E, more hydrophilic agents like alpha-lipoic acid and acetyl cysteine, and transition metal chelators that inhibit autoxidation. In the long-term, elevated ROS cause cumulative damage to neurons and Schwann cells, however, they also have a deleterious effect on nerve blood flow in the short term. This causes endoneurial hypoxia, which is responsible for early NCV deficits. Antioxidant treatment corrects the blood flow deficit and promotes normal endoneurial oxygenation. ROS cause antioxidant-preventable vascular endothelium abnormalities, neutralizing nitric oxide mediated vasodilation and increasing reactivity to vasoconstrictors. Unsaturated fatty acids are a major target for ROS and essential fatty acid metabolism is impaired by diabetes. Gamma-linolenic acid stimulates vasodilator prostanoid production, and there are marked synergistic interactions between gamma-linolenic acid and antioxidants. This has encouraged the development of novel drugs such as ascorbyl-gamma-linolenic acid and gamma-linolenic acid-lipoic acid with enhanced therapeutic potential.

Our study aimed to investigate the effects of acupuncture on diabetic peripheral neuropathy. We compared 42 cases treated with acupuncture with 21 cases exposed to sham acupuncture and observed the effects on nerve conduction velocity and a variety of subjective symptoms associated with diabetic peripheral neuropathy. Three of the six measures of motor nerves, and two measures of sensory function, demonstrated significant improvement (p<0.05) over the 15-day treatment period in the acupuncture group, while no motor or sensory function significantly improved in the sham acupuncture group. There were also significant differences in vibration perception threshold between the groups (p<0.05) and when compared to the baseline levels (p<0.01) in the acupuncture group. Acupuncture was significantly more effective than sham for treatment of numbness of the lower extremities, spontaneous pain in the lower extremities, rigidity in the upper extremities and alterations in temperature perception in the lower extremities after therapy. Our pilot study has, therefore, provided evidence that acupuncture may be clinically useful for the radical treatment of diabetic peripheral neuropathy.

Our study aimed to investigate the effects of acupuncture on diabetic peripheral neuropathy. We compared 42 cases treated with acupuncture with 21 cases exposed to sham acupuncture and observed the effects on nerve conduction velocity and a variety of subjective symptoms associated with diabetic peripheral neuropathy. Three of the six measures of motor nerves, and two measures of sensory function, demonstrated significant improvement (p<0.05) over the 15-day treatment period in the acupuncture group, while no motor or sensory function significantly improved in the sham acupuncture group. There were also significant differences in vibration perception threshold between the groups (p<0.05) and when compared to the baseline levels (p<0.01) in the acupuncture group. Acupuncture was significantly more effective than sham for treatment of numbness of the lower extremities, spontaneous pain in the lower extremities, rigidity in the upper extremities and alterations in temperature perception in the lower extremities after therapy. Our pilot study has, therefore, provided evidence that acupuncture may be clinically useful for the radical treatment of diabetic peripheral neuropathy.

AIMS:To examine the role of acupuncture in the treatment of diabetic painful neuropathy (DPN) using a single-blind, placebo-controlled RCT and to collect data that would be required in a future definitive study of the efficacy of acupuncture in DPN.

METHODS:45 patients were allocated to receive a 10-week course either of real (53%) or sham (47%) acupuncture. Five standardised acupuncture points on the lower limb of each leg were used in the study: LR3, KI3, SP6, SP10 and ST36. Outcome measures included the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, lower limb pain (Visual Analogue Scale, VAS); Sleep Problem Scale (SPS); Measure Yourself Medical Outcome Profile (MYMOP); 36-item Short Form 36 Health Survey and resting blood pressure (BP).

RESULTS:Over the 10-week treatment period, small improvements were seen in VAS -15 (-26 to -3.5), MYMOP -0.89 (-1.4 to -0.3), SPS -2.5 (-4.2 to -0.82) and resting diastolic BP -5.2 (-10.4 to -0.14) in the true acupuncture group. In contrast, there was little change in those receiving sham acupuncture. A moderate treatment effect in favour of active acupuncture was detected in MYMOP scores -0.66 (-0.96 to -0.35) but non-significant effect sizes in LANSS Pain Scale -0.37 (-2.2 to 1.4), resting diastolic BP -0.50 (-3.0 to 1.99) and the SPS -0.51 (-2.2 to 1.16).

CONCLUSIONS:We have demonstrated the practicality and feasibility of acupuncture as an additional treatment for people with DPN. The treatment was well tolerated with no appreciable side effects. Larger randomised trials are needed to confirm the clinical and cost-effectiveness of acupuncture in the treatment of DPN.

TRIAL REGISTRATION NUMBER:ISRCTN number: 39740785.

AIMS:To examine the role of acupuncture in the treatment of diabetic painful neuropathy (DPN) using a single-blind, placebo-controlled RCT and to collect data that would be required in a future definitive study of the efficacy of acupuncture in DPN.

METHODS:45 patients were allocated to receive a 10-week course either of real (53%) or sham (47%) acupuncture. Five standardised acupuncture points on the lower limb of each leg were used in the study: LR3, KI3, SP6, SP10 and ST36. Outcome measures included the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale, lower limb pain (Visual Analogue Scale, VAS); Sleep Problem Scale (SPS); Measure Yourself Medical Outcome Profile (MYMOP); 36-item Short Form 36 Health Survey and resting blood pressure (BP).

RESULTS:Over the 10-week treatment period, small improvements were seen in VAS -15 (-26 to -3.5), MYMOP -0.89 (-1.4 to -0.3), SPS -2.5 (-4.2 to -0.82) and resting diastolic BP -5.2 (-10.4 to -0.14) in the true acupuncture group. In contrast, there was little change in those receiving sham acupuncture. A moderate treatment effect in favour of active acupuncture was detected in MYMOP scores -0.66 (-0.96 to -0.35) but non-significant effect sizes in LANSS Pain Scale -0.37 (-2.2 to 1.4), resting diastolic BP -0.50 (-3.0 to 1.99) and the SPS -0.51 (-2.2 to 1.16).

CONCLUSIONS:We have demonstrated the practicality and feasibility of acupuncture as an additional treatment for people with DPN. The treatment was well tolerated with no appreciable side effects. Larger randomised trials are needed to confirm the clinical and cost-effectiveness of acupuncture in the treatment of DPN.

TRIAL REGISTRATION NUMBER:ISRCTN number: 39740785.