vitamin-b-12 and Diabetic-Neuropathies

Vitamin B

Topics: Antioxidants; Diabetes Mellitus; Diabetic Neuropathies; Humans; Methionine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

In Asian countries, herbal medicines have been used to treat diabetic peripheral neuropathy (DPN) as an adjunctive therapy. This review aims to assess the effectiveness and safety of herbal medicines for the treatment of DPN.. A literature search was conducted on PubMed, Embase, CENTRAL, Scopus, CINAHL, CNKI, DBPIA, and OASIS for randomized controlled trials that evaluated the effects of herbal medicines on DPN. The oral methylcobalamin administered group was selected as the control. The primary outcome measure was nerve conduction velocity (NCV), and the secondary outcome measure was the total efficacy rate (TER). The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. A meta-analysis was conducted using Review Manager 5.4.1 software.. Seventy-two RCTs with a total of 6260 patients were included. The meta-analysis showed that herbal medicine and co-administration of herbal medicine and methylcobalamin (CHM) treatment for DPN significantly increased the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of the median and common peroneal nerves than methylcobalamin treatment alone. Herbal medicine and CHM treatment for DPN also significantly improved the TER compared to the control group. Herbal medicine and CHM treatment was found to be relatively safe.. Our study suggests that herbal medicine and CHM might be more effective than methylcobalamin alone in the management of DPN. Further rigorous studies should be conducted to make more definite conclusions.

Topics: Diabetes Mellitus; Diabetic Neuropathies; Drugs, Chinese Herbal; Humans; Neural Conduction; Plants, Medicinal; Vitamin B 12

Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate-activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.. 二甲双胍是一种广泛用于治疗2型糖尿病的降糖药物。它已被证明具有镇痛和神经保护作用。二甲双胍可以逆转啮齿类动物的疼痛，如糖尿病性神经痛、化疗药物引起的神经性疼痛、炎症性疼痛、手术切口引起的疼痛。然而，在临床使用中，二甲双胍与血浆维生素B12水平降低有关，这可能会进一步加剧神经病变。在啮齿动物糖尿病模型中，二甲双胍通过激活AMPK、清除MGO、降低胰岛素抵抗和神经炎症发挥神经保护和镇痛作用。本文还总结了二甲双胍对糖尿病患者的神经系统不良反应。此外，二甲双胍是否有两性区别还有待进一步研究。.

Topics: Adenosine Monophosphate; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Hypoglycemic Agents; Metformin; Neuroprotective Agents; Pain; Protein Kinases; Vitamin B 12

Diabetic peripheral neuropathy (DPN) is a common and severe complication that affects 50% of people with diabetes. Painful DPN is reported to occur in 16% to 24% of people with diabetes. A complete and comprehensive management strategy for the prevention and treatment of DPN, whether painful or not, has not yet been defined.Research into treatment for DPN has been characterised by a series of failed clinical trials, with few noteworthy advances. Strategies that support peripheral nerve regeneration and restore neurological function in people with painful or painless DPN are needed. The amino acid acetyl-L-carnitine (ALC) plays a role in the transfer of long-chain fatty acids into mitochondria for β-oxidation. ALC supplementation also induces neuroprotective and neurotrophic effects in the peripheral nervous system. Therefore, ALC supplementation targets several mechanisms relevant to potential nerve repair and regeneration, and could have clinical therapeutic potential. There is a need for a systematic review of the evidence from clinical trials.. To assess the effects of ALC for the treatment of DPN.. On 2 July 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We checked references, searched citations, and contacted study authors to identify additional studies.. We included randomised controlled trials (RCTs) and quasi-RCTs of ALC compared with placebo, other therapy, or no intervention in the treatment of DPN. Participants could be of any sex and age, and have type 1 or type 2 diabetes mellitus, of any severity, with painful or painless DPN. We accepted any definition of minimum criteria for DPN, in accordance with the Toronto Consensus. We imposed no language restriction.Pain was the primary outcome, measured as the proportion of participants with at least 30% (moderate) or 50% (substantial) decrease in pain over baseline, or as the score on a visual analogue scale (VAS) or Likert scale for pain.. We followed standard Cochrane methods.. We included four studies with 907 participants, which were reported in three publications. Three trials studied ALC versus placebo (675 participants); in one trial the dose of ALC was 2000 mg/day, and in the other two trials, it was 1500 mg/day or 3000 mg/day. The fourth trial studied ALC 1500 mg/day versus methylcobalamin 1.5 mg/day (232 participants). The risk of bias was high in both trials of different ALC doses and low in the other two trials.No included trial measured the proportion of participants with at least moderate (30%) or substantial (50%) pain relief. ALC reduced pain more than placebo, measured on a 0- to 100-mm VAS (MD -9.16, 95% CI -16.76 to -1.57; three studies; 540 participants; P = 0.02; I² = 56%; random-effects; very low-certainty evidence; a higher score indicating more pain). At doses of 1500 mg/day or less, the VAS score after ALC treatment was little different from placebo (MD -0.05, 95% CI -10.00 to 9.89; two studies; 159 participants; P = 0.99; I² = 0%), but at doses greater than 1500 mg/day, ALC reduced pain more than placebo (MD -14.93, 95% CI -19.16 to -10.70; three studies; 381 participants; P < 0.00001; I² = 0%). This subgroup analysis should be viewed with caution as the evidence was even less certain than the overall analysis, which was already of very low certainty.Two placebo-controlled studies reported that vibration perception improved after 12 months. We graded this evidence as very low certainty, due to inconsistency and a high risk of bias, as the trial authors did not provide any numerical data. The placebo-controlled studies did not measure functional impairment and disability scores. No study used validated symptom scales. One study performed sensory testing, but the evidence was very uncertain.The fourth included study compared ALC with methylcobalamin, but did not report effects on pain. There was a reduction from baseline to 24 weeks in functional impairment and disability, based on the change in mean Neuropathy Disability Score (NDS; scale from zero to 10), but there was no important difference between the ALC group (mean score 1.66 ± 1.90) and the methylcobalamin group (mean score 1.35 ± 1.65) groups (P = 0.23; low-certainty evidence).One placebo-controlled study reported that six of 147 participants in the ALC > 1500 mg/day group (4.1%) and two of 147 participants in the placebo group (1.4%) discontinued treatment because of adverse events (headache, facial paraesthesia, and gastrointestinal disorders) (P. We are very uncertain whether ALC causes a reduction in pain after 6 to 12 months' treatment in people with DPN, when compared with placebo, as the evidence is sparse and of low certainty. Data on functional and sensory impairment and symptoms are lacking, or of very low certainty. The evidence on adverse events is too uncertain to make any judgements on safety.

Topics: Acetylcarnitine; Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Placebos; Randomized Controlled Trials as Topic; Sensation; Vibration; Vitamin B 12

Fasudil (F) plus methylcobalamin (M) or lipoic acid (L) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in numerous studies. However, the effect of the combined use still remains dubious.. The aim of this report was to evaluate the efficacy of F plus M or L (F + M or F + L) for the treatment of DPN compared with that of M or L monotherapy, respectively, in order to provide the basis and reference for clinical rational drug use.. Randomized controlled trials (RCTs) of F for DPN published up to September 2017 were searched. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (NCVs) (MNCVs), median sensory NCV (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects.. Thirteen RCTs with 1148 participants were included. Clinical efficacy of F + M combination therapy was significantly better than M monotherapy (8 trials; RR 1.26, 95% CI 1.17-1.35, P < .00001, I = 0%), the efficacy of F + L combination therapy was also obviously better than L monotherapy (4 trials; RR 1.27, 95% CI 1.16-1.39, P < .00001, I = 0%). Compared with monotherapy, the pooled effects of combination therapy on NCV were (MD 6.69, 95% CI 4.74-8.64, P < .00001, I = 92%) for median MNCV, (MD 6.71, 95% CI 1.77-11.65, P = .008, I = 99%) for median SNCV, (MD 4.18, 95% CI 2.37-5.99, P < .00001, I = 94%) for peroneal MNCV, (MD 5.89, 95% CI 3.57-8.20, P < .00001, I = 95%) for peroneal SNCV. Furthermore, there were no serious adverse events associated with drug intervention.. Combination therapy with F plus M or L was superior to M or L monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients, respectively. Moreover, no serious adverse events occur in combination therapy.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Antioxidants; Calcium Channel Blockers; Diabetic Neuropathies; Drug Therapy, Combination; Female; Humans; Male; Neural Conduction; Thioctic Acid; Treatment Outcome; Vitamin B 12

Prostaglandin E1 (P) or methylcobalamin (M) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in many clinical trial reports. However, the combined effects of 2 drugs still remain dubious.. The aim of this report was to evaluate the efficacy of M plus P (M + P) for the treatment of DPN compared with that of P monotherapy, in order to provide a reference resource for rational drug use.. Randomized controlled trials (RCTs) of M + P for DPN published up to September 2017 were searched. Risk ratio (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Subgroup and sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects.. Sixteen RCTs with 1136 participants were included. Clinical efficacy of M + P combination therapy was significantly better than P monotherapy (fifteen trials; RR 1.25, 95% CI 1.18-1.32, P < .00001, I = 27%). Compared with P monotherapy, the pooled effects of M + P combination therapy on nerve conduction velocity were (MD 6.29, 95% CI 4.63-7.94, P < .00001, I = 90%) for median MNCV, (MD 5.68, 95% CI 3.53-7.83, P < .00001, I = 94%) for median SNCV, (MD 5.36, 95% CI 3.86-6.87, P < .00001, I = 92%) for peroneal MNCV, (MD 4.62, 95% CI 3.48-5.75, P < .00001, I = 86%) for peroneal SNCV. There were no serious adverse events associated with drug intervention.. M + P combination therapy was superior to P monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients. Moreover, no serious adverse events occur in combination therapy.

Topics: Alprostadil; Diabetic Neuropathies; Drug Therapy, Combination; Female; Humans; Male; Neural Conduction; Randomized Controlled Trials as Topic; Treatment Outcome; Vitamin B 12

The association between serum folate and vitamin B12 levels and the risk of diabetic peripheral neuropathy (DPN) remains unclear. This meta-analysis included 16 studies of serum folate levels (1190 cases and 1501 controls) and 18 studies of serum vitamin B12 levels (1239 cases and 1562 controls) in patients with type 2 diabetes mellitus (T2DM). Reduced serum levels of folate and vitamin B12 were found in patients with T2DM and DPN compared with patients with T2DM but without DPN; weighted mean difference (WMD) = -1.64 (95% confidence interval [CI] = -2.46, -0.81) and WMD = -70.86 (95% CI = -101.55, -40.17), respectively. A subgroup analysis confirmed these associations in the Chinese population, but not in the Caucasian and mixed populations. In conclusion, these findings support the need for further controlled studies in defined patient populations and the importance of monitoring serum folate and vitamin B12 levels in patients with T2DM.

Topics: Aged; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Humans; Male; Middle Aged; Publication Bias; Vitamin B 12

Vitamin B12 deficiency has been associated with significant neurological pathology, especially peripheral neuropathy. This review aims to examine the existing evidence on the effectiveness of vitamin B12 supplementation for the treatment of diabetic peripheral neuropathy. A search of PubMed and the Cochrane Central Register of Controlled Trials for all relevant randomised controlled trials was conducted in December 2014. Any type of therapy using vitamin B12 or its coenzyme forms was assessed for efficacy and safety in diabetics with peripheral neuropathy. Changes in vibration perception thresholds, neuropathic symptoms and nerve conduction velocities, as well as the adverse effects of vitamin B12 therapy, were assessed. Four studies comprising 363 patients met the inclusion criteria. This review found no evidence that the use of oral vitamin B12 supplements is associated with improvement in the clinical symptoms of diabetic neuropathy. Furthermore, the majority of studies reported no improvement in the electrophysiological markers of nerve conduction.

Topics: Diabetic Neuropathies; Dietary Supplements; Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins

This report was to evaluate the efficacy of lipoic acid, prostaglandin E1 and methylcobalamin (L+P+M) for the treatment of diabetic peripheral neuropathy (DPN) in comparison with that of prostaglandin E1 plus methylcobalamin (P+M), in order to provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of L+P+M for DPN published up to 3rd August, 2014 were searched. A random or fixed effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95% confidence interval (CI). Eighteen RCTs with 1410 participants were included. Clinical efficacy of L+P+M therapy was significantly better than P+M therapy (fifteen trials; RR 1.32, 95% CI 1.24-1.41, P<0.00001, I(2)=32%). As compared with P+M therapy, the pooled effects of L+P+M therapy on nerve conduction velocities (NCVs) were (fifteen trials; MD 4.70, 95% CI 3.77-5.63, P<0.00001, I(2)=79%) for median MNCV, (thirteen trials; MD 4.73, 95% CI 3.69-5.77, P<0.00001, I(2)=85%) for median SNCV, (sixteen trials; MD 4.22, 95% CI 3.32-5.12, P<0.00001, I(2)=83%) for peroneal MNCV, (fourteen trials; MD 3.09, 95% CI 2.04-4.14, P<0.00001, I(2)=82%) for peroneal SNCV. There was no serious adverse events associated with drugs intervention. L+P+M therapy was superior to P+M therapy for improvement of clinical efficacy and NCVs in DPN patients. These findings should be further verified by high-quality RCTs.

Topics: Alprostadil; Diabetic Neuropathies; Drug Therapy, Combination; Humans; Neural Conduction; Randomized Controlled Trials as Topic; Thioctic Acid; Vitamin B 12

A meta-analysis on combined therapy of diabetic peripheral neuropathy (DPN) with breviscapine and mecobalamin was performed to evaluate the efficacy of this therapy.. Six English databases (Medline, Cochrane Library, PubMed, EMBASE, Web of Science, and CINAHL) and four Chinese databases (China National Knowledge Infrastructure, VIP Journals Database, CBM, and Wanfang database) were searched for studies on the clinical trials in which DPN was treated with breviscapine and mecobalamin, and RevMan 5.1 package was employed for analyzing pooled trials and publication bias.. A total of 17 articles including 1398 DPN patients were identified. Homogeneity was observed among different studies (P = 0.74). The efficacy of combined therapy with breviscapine and mecobalamin was significantly better than that in control group [P < 0.0001 (OR = 5.01, 95% CI: 3.70-6.78)].. Available findings suggest that the therapeutic efficacy of breviscapine combining mecobalamin is superior to mecobalamin alone, and this strategy is required to be popularized in clinical practice.

Topics: China; Diabetic Neuropathies; Drug Therapy, Combination; Female; Flavonoids; Humans; Male; Vitamin B 12

This study aimed to compare the efficacy and safety of prostaglandin E1 plus methylcobalamin (PGE1-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN). We searched published randomized controlled trials (RCTs) of PGE1 combined with MC for DPN up to June 1, 2013. Data were extracted to evaluate methodological quality and describe characteristics of studies in duplicate. A random or a fixed effect model was used to analyze outcomes which were expressed as relative risk (RR) or mean difference with a 95 % confidence interval (CI). All data were analyzed using Review Manager 5.2 software. Twenty-six RCTs involving 2,107 individuals were included. Meta-analysis showed that PGE1-MC combination therapy was significantly better than MC monotherapy (RR = 1.40; 95 % CI 1.33-1.48) on efficacy. The weighted mean differences in nerve conduction velocities (NCVs) were 6.72 (95 % CI: 5.42-8.02) for median motor nerve conduction velocity (MNCV), 5.13 (CI 4.13-6.13) for median sensory nerve conduction velocity (SNCV), 5.74 (CI 4.87-6.61) for peroneal MNCV and 4.62 (CI 3.89-5.34) for peroneal SNCV in favor of the PGE1 + MC combination group. Moreover, there were no serious adverse events in both groups during the treatment period. The results of the meta-analysis show that treatment with PGE1-MC is safe and can gain better outcomes in neuropathic symptoms and NCVs compared with MC alone. However, the conclusion may not be strong because most of the studies included in this meta-analysis have poor methodological quality.

Topics: Alprostadil; Diabetic Neuropathies; Drug Therapy, Combination; Humans; Median Nerve; Neural Conduction; Peripheral Nervous System Diseases; Treatment Outcome; Vitamin B 12

To compare the efficacy and safety of daily lipoic acid (300-600 mg i.v.) plus methylcobalamin (500-1000 mg i.v. or im.) (LA-MC) with that of methylcobalamin alone (MC) on diabetic peripheral neuropathy (DPN).. Electronic database were searched for studies published up to November 1, 2012 and study quality was assessed in duplicate. A random or a fixed effect model was used to analyse outcomes which were expressed as risk ratios (RRs) or mean difference (MD). I(2) statistic was used to assess heterogeneity.. Seventeen studies were included. Combined data from all studies showed that the LA-MC combination therapy was significantly superior to MC monotherapy (RR=1.47; 95% CI: 1.37-1.58). Superiority of the LA-MC combination was shown in nerve conduction velocity (NCV) with WMDs of 6.89 (95% CI: 4.24-9.73) for median motor nerve conduction velocity (MNCV), 5.24 (4.14-6.34) for median sensory nerve conduction velocity (SNCV), 4.34 (3.03-5.64) for peroneal MNCV, and 4.53 (3.2-5.85) for peroneal SNCV. There were no serious adverse events associated with treatment.. The results of the meta-analysis show that treatment with LA-MC for 2-4 weeks is associated with better outcomes in NCV and neuropathic symptoms relative to MC treatment. However larger well-designed studies are required to confirm this conclusion.

Topics: Diabetic Neuropathies; Drug Therapy, Combination; Humans; Peripheral Nervous System Diseases; Thioctic Acid; Vitamin B 12

Mecobalamin, one of the coenzyme forms of vitamin B(12), acts as an important cofactor in the activities of B(12)-dependent methyltransferases. Since the discovery of mecobalamin, it has been applied mainly in the treatment of hyperhomocysteinaemia and peripheral neuropathy. However, there is still lack of a systemic review on the clinical administration of mecobalamin and its potential mechanism.. To review the mechanism, clinical efficacy and safety of mecobalamin in the treatment of hyperhomocysteinaemia and peripheral neuropathy.. First, the potential mechanism, pharmacokinetics and metabolism of mecobalamin were clarified. In addition, the clinical administration including efficacy, safety and tolerability of mecobalamin as monotherapy or combined therapy in the treatment of hyperhomocysteinaemia and peripheral neuropathy were also detailed.. Although both monotherapy and combined therapy can lower plasma/serum homocysteine levels and improve the neuropathic symptoms, combined therapy with other B vitamins seems to be more effective. However, more precise, double-blind and randomised control studies are necessary to confirm the efficacy of mecobalamin on hyperhomocysteinaemia, peripheral neuropathy interaction, and cardiovascular, neurological and osteoporotic mortality or morbidity.

Topics: Aged; Alprostadil; Animals; Cobamides; Coenzymes; Diabetic Neuropathies; Drug Administration Routes; Drug Therapy, Combination; Female; Folic Acid; Humans; Hyperhomocysteinemia; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Metformin; Methionine; Methyltransferases; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Renal Dialysis; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6

The clinical effectiveness of vitamin B12 and its active coenzyme form on diabetic neuropathy is uncertain. Therefore, we searched the English- and non-English-language literature on this topic by using MEDLINE (Ovid, PubMed), the Cochrane Controlled Trials Register, and related papers. We identified seven randomized controlled trials from June 1954 to July 2004 and reviewed them for the clinical effectiveness of vitamin B12 according to the following parameters: Measurement scales of somatic and autonomic symptoms or signs; vibrometer-detected thresholds of vibration perception; and, electrophysiologic measures such as nerve conduction velocities and evoked potentials. Three studies involved the use of vitamin B complex (including B12) as the active drug, and four used methylcobalamin. Two studies were of fairly good quality (Jadad score = 3/5), and five were of poor quality (Jadad score < or = 2/5). Both the vitamin B12 combination and pure methylcobalamin had beneficial effects on somatic symptoms, such as pain and paresthesia. In three studies, methylcobalamin therapy improved autonomic symptoms. Effects on vibration perception and electrophysiological measures were not consistent. With both the vitamin B12 combination and pure methylcobalamin, symptomatic relief was greater than changes in electrophysiological results. However, more high-quality, double-blind randomized controlled trials are needed to confirm the effects of vitamin B12 on diabetic neuropathy.

Topics: Diabetic Neuropathies; Humans; Randomized Controlled Trials as Topic; Vitamin B 12

Topics: Achilles Tendon; Aldehyde Reductase; Antidepressive Agents, Tricyclic; Diabetic Neuropathies; Diagnosis, Differential; Electrodiagnosis; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Humans; Hypoglycemic Agents; Ketamine; Neural Conduction; Reflex, Abnormal; Vibration; Vitamin B 12

Topics: Aldehyde Reductase; Chronic Disease; Diabetic Neuropathies; Diagnosis, Differential; Enzyme Inhibitors; Fludrocortisone; Humans; Hypoglycemic Agents; Mexiletine; Nerve Growth Factor; Platelet Aggregation Inhibitors; Recombinant Proteins; Severity of Illness Index; Vasodilator Agents; Vitamin B 12

Topics: Alprostadil; Diabetic Neuropathies; Diagnosis, Differential; Humans; Neural Conduction; Peripheral Nervous System; Prognosis; Vitamin B 12

BACKGROUND Acupoint injection is a therapeutic method that combines acupuncture and Western medicine and shows good curative effects for neuropathies. This study aimed to explore the efficacy of acupoint injection for treating diabetic peripheral neuropathy (DPN) by magnetic resonance neuroimaging (MRN). MATERIAL AND METHODS Forty patients with DPN were randomly divided into an acupoint injection group (AI; n=20) and intramuscular injection group (MI; n=20). The AI group received an acupoint injection of mecobalamin at acupoint Zusanli (S36); the MI group received intramuscular injection of mecobalamin. The curative effect was evaluated by the Toronto Clinical Neuropathy Score and diffusion tensor imaging (DTI). RESULTS The neuropathy scores of both groups decreased from baseline (AI 9.31±2.36; MI 9.34±2.54) to after the 2-week treatment (AI 7.12±1.87; MI 7.86±2.11); the differences were not significant. The fractional anisotropy (FA) value showed significant differences on the common peroneal nerve (AI 0.36±0.04; MI 0.31±0.05; P<0.05) and tibial nerve (AI 0.38±0.07; MI 0.34±0.06; P<0.05) after treatment. Likewise, apparent diffusion coefficient (ADC) values between groups showed significant differences for the common peroneal nerve (AI 1.44±0.17×10⁻³ mm²/s; MI 1.61±0.20×10⁻³ mm²/s; P<0.05) and tibial nerve (AI 1.54±0.22×10-3 mm²/s; MI 1.60±0.17 10⁻³ mm²/s; P<0.05). CONCLUSIONS Patients with DPN showed lower nerve FA and higher ADC in DTI-MRN. The acupoint injection of mecobalamin could treat DPN and repair the damaged nerves, which was shown by elevated FA and lowered ADC. Our study provides clinical evidence for the application of acupoint injection therapy and the evaluation of DPN by MRN.

Topics: Acupuncture Points; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diffusion Tensor Imaging; Humans; Injections, Intramuscular; Vitamin B 12

To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 μg/day for one year in patients with diabetic neuropathy (DN).. In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score).. B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up,. The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Topics: Cholesterol; Creatinine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Female; Folic Acid; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linear Models; Male; Middle Aged; Prospective Studies; Quality of Life; Triglycerides; Vitamin B 12

The most common and bothersome lower urinary tract complication of diabetes mellitus is diabetic neurogenic bladder (DNB). Acupuncture has certain advantages in treating bladder dysfunction including urinary retention and incontinence. Therefore, we think that electroacupuncture (EA) may be beneficial to DNB patients. However, it is not clear whether EA combined with basic western medicine could optimize the therapeutic effect for DNB.. This is a sham-controlled, patient-blinded, pioneer randomized controlled trial (RCT). One hundred fifty eligible patients will be randomly divided into 3 groups: A. basic western medicine (BWC), B. EA with BWC, C. sham EA with BWC. EA treatment will be given twice a week for 12 weeks at bilateral BL23, BL32, BL33, and BL35. The BWC group will received Alpha-lipoic acid (ALA) and methylcobalamin (MC) treatment for 12 weeks, 2 treatment sessions per week. The primary outcome is scored by the 72-hour bladder diary (72h-BD). The secondary outcomes will be scored by the American Urological Association symptom index (AUA-SI), Post-void residual urine volume (PVR) and urodynamic tests. All the assessments will be conducted at baseline and the 12th weeks after the intervention starts. The follow-up assessments will be performed with 72h-BD and AUA-SI in the 4th, 12th, and 24th weeks after intervention ends.. This trial protocol provides an example of the clinical application acupuncture treatment in the management of DNB. This RCT will provide us information on the effect of treating DNB patients with only acupuncture, western medicine therapy (ALA + MC) as well as the combination of both. The additive effect or synergistic effect of acupuncture and basic western medicine will then be analyzed.. Chinese Clinical Trial Registry, ChiCTR2000030421.

Topics: Adolescent; Adult; Aged; Diabetic Neuropathies; Electroacupuncture; Female; Humans; Male; Middle Aged; Single-Blind Method; Thioctic Acid; Treatment Outcome; Urinary Bladder, Neurogenic; Urodynamics; Vitamin B 12; Vitamin B Complex; Young Adult

To evaluate the effects of topical citicoline and vitamin B12 (Cit-B12: OMK2, Omikron Italia srl, Italy) on corneal innervation of patients with diabetic neuropathy.. This prospective, randomized, double blind, placebo-controlled study included 30 patients randomised with a 2:1 ratio to Cit-B12 or placebo 3 times daily for 18 months. At baseline and at months 4, 8, 12, 18 patients underwent the Ocular Surface Disease Index questionnaire (OSDI), tear break-up time, evaluation of corneal and conjunctival staining, Schirmer I test, Cochet-Bonnet esthesiometry, and confocal biomicroscopy of corneal sub-basal plexus (SBP). Fiber lenght density (FLD) was calculated using NeuronJ and expressed in mm/mm2. Raw data and differences from baseline were analysed in the two groups.. 29/30 patients concluded the study. The two groups had similar FLD at baseline; it progressively improved up to month 18 in both groups (Cit-B12, p < 0.0001; controls, < 0.0001-0.03); improvement at month 18 vs baseline was higher in Cit-B12 than placebo (33% vs 15%, p = 0.04). A progressive amelioration of corneal sensitivity (baseline, 28 ± 18 mm; month 18, 52 ± 10 mm, p < 0.0001), conjunctival staining (P = 0.04) and OSDI questionnaire (P = 0.05) were shown on Cit-B12 group alone. Both treatments were well tolerated and adherence during the study was high.. Cit-B12 ameliorated both morphology and function of corneal nerves in patients with diabetes, thus suggesting a neuroregenerative effect.. Trial registration NCT03906513 , retrospectively registered on 08 April 2019.

Topics: Cornea; Cytidine Diphosphate Choline; Diabetes Mellitus; Diabetic Neuropathies; Dry Eye Syndromes; Humans; Prospective Studies; Tears; Vitamin B 12

Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM).. The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed.. After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI - 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference - 0.33 V (95% CI - 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA. Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA

Topics: Aged; Autonomic Nervous System Diseases; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Hypotension, Orthostatic; Insulin; Male; Metformin; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Standing Position; Vitamin B 12

To investigate the efficacy of Superoxide Dismutase, Alpha Lipoic Acid, Acetyl L-Carnitine, and Vitamin B12 (B12) in one tablet in Diabetic Neuropathy (DN).. In this prospective, double-blind, placebo-controlled study, 85 patients with Diabetes Mellitus Type 2 (DMT2) were randomly assigned, either to receive the combination of four elements (active group,. At follow-up, BIO, MNSIQ, QL, PAIN, and SNCV, SNAP, and B12 levels had significantly improved inactive group (. The combination of the four elements in one tablet for 12 months in patients with DMT2 improved all indices of peripheral neuropathy, including SNAP and SNCV, pain, and Quality of Life perception, except CARTs and MNSIE.

Topics: Aged; Carnitine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Neural Conduction; Pain Measurement; Prospective Studies; Quality of Life; Reflex; Superoxide Dismutase; Thioctic Acid; Treatment Outcome; Vitamin B 12

In diabetic polyneuropathy (DPN) patients, the effect of folic acid and homocysteine has been related to components of nerve conduction velocity (NCV). The objective of this study was to determine the effect of folic acid supplementation on NCV in DPN patients.. Patients were randomized to receive either 1 mg of folic acid (n = 40) or placebo (n = 40) for 16 weeks. Blood samples were collected to assess serum folic acid and homocysteine concentrations, and NCV was performed for assessment of diabetic neuropathy.. At 16 weeks, in the supplemented group, serum levels of folic acid (p < 0.001) increased, homocysteine concentrations decreased (p < 0.001), with no change in serum vitamin B12 levels. There was a significant increase in sensory sural amplitude (p < 0.001), and components of motor nerves, including amplitude (p = 0.001) and velocity (p < 0.001), but decreased onset latency of peroneal (p = 0.019) and tibial (p = 0.011) motor nerves.. Our data suggest that supplementation with 1 mg of folic acid for 16 weeks may be useful for enhancing NCV in DPN patients.

Topics: Adult; Diabetic Neuropathies; Dietary Supplements; Double-Blind Method; Electromyography; Female; Folic Acid; Homocysteine; Humans; Male; Middle Aged; Neural Conduction; Reaction Time; Severity of Illness Index; Statistics, Nonparametric; Vitamin B 12

Diabetic hyperglycemia damages peripheral nerves by triggering ischemia, oxidative stress, and inflammation. Alpha-lipoic acid (ALA) and methylcobalamin (MC) are known to improve signs of diabetic peripheral neuropathy (DPN), possibly by enhancing neural and vascular endothelial cell metabolism and antioxidant capacity. We evaluated differences in efficacy following short-term MC or ALA treatment on DPN symptoms to guide clinical drug selection.. Forty DPN patients were randomly divided into MC and ALA treatment groups (both N.=20) and assessed by the Toronto Clinical Neuropathy Scoring System (TCSS), total symptom score (TSS), visual analog scale (VAS) of positive symptoms, and easy sensory test (EST) for negative symptoms before and after 2 weeks of treatment. Serum malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured.. Neuropathy as measured by TCSS, TSS, and VAS scores was significantly reduced by both treatments (P<0.05) but magnitude varied by symptom. The VAS score reductions for burning and pain were significantly greater following ALA (P<0.01), while MC reduced numbness and paresthesia VAS scores to a slightly greater extent than ALA (P>0.05). Numbers of abnormal (low-response) points for pressure and pinprick sensation were reduced by MC but not by ALA, while both treatments induced a significant reduction in vibratory perception threshold (P<0.01). Neither MC nor ALA improved temperature sensation or tendon reflexes (P>0.05). Alpha-lipoic acid, increased SOD and reduced MDA (P<0.05), indicating enhanced antioxidant capacity, while MC had no effect.. Due to differences in efficacy, MC or ALA should be chosen according to the symptoms of individual patients.

Topics: Aged; Antioxidants; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Pain Measurement; Peripheral Nervous System Diseases; Thioctic Acid; Treatment Outcome; Vitamin B 12

Painful diabetic neuropathy (PDN) is a prevalent and impairing disorder. The objective of this study was to show the efficacy and safety of gabapentin (GBP) plus complex B vitamins: thiamine (B1) and cyanocobalamine (B12) compared to pregabalin in patients with moderate to severe intensity PDN.. Multicenter, randomized, blind study. Two hundred and seventy patients were evaluated, 147 with GBP/B1/B12 and 123 with PGB, with a 7/10 pain intensity on the Visual Analog Scale (VAS). Five visits (12 weeks) were scheduled. The GBP/B1 (100 mg)/B12 (20 mg) group started with 300 mg at visit 1 to 3600 mg at visit 5. The PGB group started with 75 mg/d at visit 1 to 600 mg/d at visit 5. Different safety and efficacy scales were applied, as well as adverse event assessment.. Both drugs showed reduction of pain intensity, without significant statistical difference (P = 0.900). In the GBP/B1/B12 group, an improvement of at least 30% on VAS correlated to a 900 mg/d dose, compared with PGB 300 mg/d. Likewise, occurrence of vertigo was lower in the GBP/B1-B12 group, with a significant statistical difference, P = 0.014.. Our study shows that GPB/B1-B12 combination is as effective as PGB. Nonetheless, pain intensity reduction is achieved with 50% of the minimum required gabapentin dose alone (800 to 1600 mg/d) in classic NDD trials. Less vertigo and dizziness occurrence was also observed in the GBP/B1/B12 group. This trial is registered with ClinicalTrials.gov NCT01364298.

Topics: Adolescent; Adult; Aged; Amines; Cyclohexanecarboxylic Acids; Diabetic Neuropathies; Drug Combinations; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Middle Aged; Pain; Pain Measurement; Pregabalin; Thiamine; Visual Analog Scale; Vitamin B 12

To assess the efficacy and safety of acetyl-L-carnitine (ALC) on diabetic peripheral neuropathy compared with methylcobalamin (MC).. This was a multicenter, randomized, parallel-group, double-blind, double-dummy, positive-controlled, non-inferior phase II clinical trial. Diabetic patients with abnormal nerve conduction test results were randomized in a 1:1 ratio to receive oral ALC 500 mg t.i.d. or MC 0.5 mg t.i.d. for 24 weeks. The neuropathy symptom score, neuropathy disability score and neurophysiological parameters were measured during follow up.. A total of 232 patients were randomized (ALC n = 117, MC n = 115), 88% of which completed the trial. At week 24, patients from both groups had significant reductions in both neuropathy symptom score and neuropathy disability score with no significant difference between two groups (neuropathy symptom score reduction: ALC vs MC 2.35 ± 2.23, P < 0.0001 vs 2.11 ± 2.48, P < 0.0001, intergroup P = 0.38; neuropathy disability score reduction ALC vs MC 1.66 ± 1.90, P < 0.0001 vs 1.35 ± 1.65, P < 0.0001, intergroup P = 0.23). Neurophysiological parameters were also improved in both groups. No significant difference was found between groups in the development of adverse events.. ALC is as effective as MC in improving clinical symptoms and neurophysiological parameters for patients with diabetic peripheral neuropathy over a 24-week period with good tolerance.

Topics: Acetylcarnitine; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Neural Conduction; Severity of Illness Index; Treatment Outcome; Vitamin B 12

To evaluate the efficacy of internal application of Qigui Mixture (QM) and external application of Qigui Huoxue Lotion (QHL) in treating type 2 diabetic peripheral neuropathy (DNP) patients of qi-yin deficiency complicated phlegm-dampness blocking collaterals syndrome (QYD-PDBCS), and to primarily discuss its mechanism.. Totally 62 DPN patients of QYD-PDBCS were randomly assigned to the treatment group (31 cases) and the control group (31 cases). All patients received routine comprehensive therapy. Patients in the control group took Mecobalamine Tablet, 500 microg each time, 3 times per day. Patients in the treatment group additionally took QM, 200 mL per day, twice daily. Besides, they had foot bath in QHL 10 - 15 min every evening for 3 months. The efficacy was assessed by Chinese medical symptom integrals and Toronto clinical scoring system (TCSS) before treatment, 2 and 3 months after treatment. The nerve conduction velocity was determined; the serum levels of total antioxidant capacity (T- AOC), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected 2 and 3 months after treatment.. The total effective rates of Chinese medical symptom integrals and TCSS score were obviously higher in the treatment group than in the control group (P < 0.05). The nerve conduction velocity was significantly improved in the treatment group, when compared with before treatment (P < 0.01). There was statistical difference in the nerve conduction velocity difference of right median nerve motor branch, bilateral tibial nerve motor branches, bilateral common peroneal nerve motor branches, bilateral ulnar nerve sensory branches, and left tibial nerve sensory branch (P < 0.05). Compared with before treatment, serum levels of T-AOC and SOD significantly increased, and the level of MDA decreased significantly in the treatment group after 2 and 3 months of treatment (P < 0.01). But only the SOD level increased significantly in the control group (P < 0.01). There was no statistical difference in increased T-AOC level between the two groups after 2 months of treatment (P > 0.05), but there was statistical difference in increased SOD level and decreased MDA level (P < 0.05). There was statistical difference in increased T-AOC and SOD levels and decreased MDA level between the two groups after 3 months of treatment (P < 0.05). No adverse reaction occurred during the therapeutic course.. The internal application of QM and external application of QHL combined with Mecobalamine in treating DPN was safe and effective, with more significant efficacy than using Mecobalamine alone. Its mechanism might be associated with resistance to oxidative stress.

Topics: Adult; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drugs, Chinese Herbal; Female; Humans; Male; Middle Aged; Qi; Treatment Outcome; Vitamin B 12; Yin Deficiency

To determine whether a combination of L-methylfolate, methylcobalamin, and pyridoxal-5'-phosphate (LMF-MC-PLP [Metanx; Pamlab LLC, Covington, La]) improves sensory neuropathy.. This multicenter, randomized, double-blind, placebo-controlled trial involved 214 patients with type 2 diabetes and neuropathy (baseline vibration perception threshold [VPT]: 25-45 volts), who were randomly assigned to 24 weeks of treatment with either L-methylfolate calcium 3 mg, methylcobalamin 2 mg, and pyridoxal-5'-phosphate 35 mg or placebo. The primary end point was effect on VPT. Secondary end points included Neuropathy Total Symptom Score (NTSS-6) and Short Form 36 (SF-36), as well as plasma levels of folate, vitamins B(6) and B(12), methylmalonic acid (MMA), and homocysteine.. There was no significant effect on VPT. However, patients receiving LMF-MC-PLP consistently reported symptomatic relief, with clinically significant improvement in NTSS-6 scores at week 16 (P=.013 vs placebo) and week 24 (P=.033). Improvement in NTSS scores was related to baseline MMA and inversely related to baseline PLP and metformin use. Quality-of-life measures also improved. Homocysteine decreased by 2.7±3.0 μmol/L with LMF-MC-PLP versus an increase of 0.5±2.4 μmol/L with placebo (P=.0001). Adverse events were infrequent, with no single event occurring in ≥2% of subjects.. LMF-MC-PLP appears to be a safe and effective therapy for alleviation of peripheral neuropathy symptoms, at least in the short term. Additional long-term studies should be conducted, as the trial duration may have been too short to show an effect on VPT. In addition, further research on the effects in patients with cobalamin deficiency would be useful.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; Folic Acid; Humans; Male; Middle Aged; Pyridoxal Phosphate; Treatment Outcome; Vitamin B 12

To compare the differences in the therapeutic effect on diabetic peripheral neuropathy between the combined therapy of electroacupuncture and acupoint injection and the simple acupoint injection.. Under the satisfactory control of blood glucose, 60 cases of diabetic peripheral neuropathy were divided randomly into two groups, 30 cases in each one. In electroacupuncture plus acupoint injection group (group A), electroacupuncture and acupoint injection with Methylcobalamin were administered. Penetrating acupuncture was applied from Gongsun (SP 4) to Quanzhong (Extra) and from Yongquan (KI 1) to Taichong (LR 3) mainly. Acupoint injection was administered on Sanyinjiao (SP 6). In acupoint injection group (group B), only acupoint injection with Methylcobalamin was provided on Sanyinjiao (SP 6). After 2 sessions of treatment, the conduction velocity of ulnar nerve and tibial nerve was measured. The scores of Chinese medicine syndrome and diabetic peripheral neuropathy were recorded before and after treatment in two groups.. The effective rates were 90.0% (27/30) and 63.3% (19/30) in group A and group B respectively, presenting significant statistical difference (P < 0.05). After treatment, the motor nerve conduction velocity (MCV) and sensory nerve conduction velocity (SCV) of ulnar nerve and tibial nerve in group A were higher than those in group B (P < 0.05, P < 0.01). After treatment, the score of Chinese medicine syndrome in group A was lower than that in group B (14.36 +/- 1.88 vs 26.58 +/- 3.52, P < 0.01), the score of diabetic peripheral neuropathy in group A was lower than that in group B (12.86 +/- 4.28 vs 17.89 +/- 4.35, P < 0.01).. Electroacupuncture and acupoint injection with Methylcobalamin achieve a significant clinical efficacy on diabetic neuropathy and its efficacy is superior to that of simple acupoint injection with Methylcobalamin. This therapy can effectively increase nerve conduction velocity, control and relieve the symptoms of diabetic peripheral neuropathy.

Topics: Acupuncture Points; Adult; Aged; Combined Modality Therapy; Diabetic Neuropathies; Electroacupuncture; Female; Humans; Injections; Male; Middle Aged; Tibial Nerve; Vitamin B 12

To investigate the intervention of Naoxintong and mecobalamin on electrophysiological changes in diabetic peripheral neuropathy (DPN) of different Chinese medicine (CM) syndrome types.. According to syndrome differentiation, 180 patients with DPN were classified as five syndrome types. And they were treated with Naoxintong (Group A), mecobalamin (Group B), and Naoxintong + mecobalamin (Group C). Four weeks was taken as one therapeutic course, and totally three courses. Their efficacies were assessed using clinical scoring, electrophysiological examinations, and ultrasonic examinations of the blood vessel inner diameter.. (1) The motor nerve conduction velocity was obviously slowed down in the Gan-Shen deficiency syndrome (P<0.01). F-wave latency was obviously prolonged in the Gan-Shen deficiency syndrome and yang deficiency blood stasis syndrome (P<0.01). The skin sympathetic reflex latency was obviously prolonged in the qi deficiency blood stasis syndrome and phlegm stagnation collateral obstruction syndrome (P<0.01). (2) Statistical difference existed in the three groups of qi deficiency blood stasis syndrome (chi2 = 7.112, P<0.05) and Gan-Shen deficiency syndrome (chi2 =6.667, P<0.05). Of them, the total effective rate of qi deficiency blood stasis syndrome was 87.5% and the markedly effective rate 43.8% in Group A (P<0.05). The total effective rate of Gan-Shen deficiency syndrome was 100.0% and the markedly effective rate 50.0% in Group B (P<0.05). The total effective rate of qi deficiency blood stasis syndrome, yin deficiency blood stasis syndrome, phlegm stagnation collateral obstruction syndrome, yang deficiency blood stasis syndrome, and Gan-Shen deficiency syndrome was respectively 92.9%, 83.3%, 81.8%, 81.8%, and 75.0% in Group C. (3) Naoxintong and mecobalamin had some improvement of motor and sensory conduction of each CM syndrome type (P<0.05). Mecobalamin showed obvious effect on the skin sympathetic reflection (P<0.05). The nerve electrophysiological index of each syndrome types as well as the diameter of arteriae tibialis anterior could be improved in Group C (P<0.05).. Naoxintong gained better effect in treatment of DPN patients of qi deficiency blood stasis syndrome by syndrome typing. Naoxintong combined with mecobalamin could be helpful for ameliorating DPN patients of each syndrome.

Topics: Adult; Diabetic Neuropathies; Diagnosis, Differential; Drugs, Chinese Herbal; Electrophysiological Phenomena; Female; Humans; Male; Medicine, Chinese Traditional; Middle Aged; Peripheral Nervous System Diseases; Phytotherapy; Vitamin B 12

Despite many therapeutic options, painful diabetic neuropathy is still a common and challenging complication of diabetes mellitus and is often resistant to treatment with current modalities.. In this randomized, single-blind clinical trial we compared the efficacy of parenteral vitamin B(12) and nortriptyline, for symptomatic improvement of pain, paresthesia, burning, freezing, stabbing and electrical sensation. Changes in nerve conduction parameters of amplitude, duration and latency were also compared.. One hundred patients (50 in each group) completed the study. After treatment, the pain score based on a visual analogue scale decreased 3.66 units in the vitamin B(12) group and 0.84 units in the nortriptyline group (P <0.001). Similarly, the paresthesia score decreased 2.98 units versus 1.06 units (P <0.001). The decrements of tingling sensation were 3.48 units versus 1.02 units (P <0.001). Changes in vibration, position, pinprick and nerve conduction parameters were not significant in two groups.. In conclusion, vitamin B(12) is more effective than nortriptyline for the treatment of symptomatic painful diabetic neuropathy.

Topics: Adolescent; Adult; Analgesics, Non-Narcotic; Anticonvulsants; Antidepressive Agents, Tricyclic; Blood Glucose; Diabetic Neuropathies; Female; Glycated Hemoglobin; Humans; Injections, Intramuscular; Lipids; Male; Middle Aged; Neural Conduction; Neuralgia; Neurons; Nortriptyline; Pain Measurement; Paresthesia; Surveys and Questionnaires; Time Factors; Vitamin B 12; Young Adult

To assess the safety of duloxetine at a fixed-dose of 60 mg twice daily (BID) for up to 52 weeks, and compare duloxetine with routine care in the management of patients with diabetic peripheral neuropathic pain (DPNP).. Patients who completed a 13-week, randomized, double-blind, placebo-controlled acute therapy period were randomly reassigned in a 2:1 ratio to therapy with duloxetine 60 mg BID (N = 197) or routine care (N = 96) for an additional 52 weeks.. The trial included outpatients > or =18 years of age diagnosed with moderate to severe DPNP caused by type 1 or type 2 diabetes.. Fourteen patients discontinued due to adverse events or death (11 [5.6%] duloxetine- and 3 [3.1%] routine care-treated patients). There were no significant therapy-group differences observed for patients with >/=1 serious adverse event. In total, 110 (55.8%) duloxetine- and 47 (49%) routine care-treated patients had > or =1 treatment-emergent adverse event (TEAE). The TEAE with a significant therapy-group difference, with patients in the duloxetine therapy group experiencing a higher percentage of events, was asthenia (11 [5.6%] duloxetine- vs no routine care-treated patients). Duloxetine did not appear to adversely affect lipid profiles, or nerve or eye function. There were no significant therapy-group differences observed in mean change in systolic blood pressure, weight, or electrocardiogram parameters. Significant therapy-group differences were observed in favor of duloxetine in the SF-36 physical component summary score, and subscale scores of physical functioning, bodily pain, mental health, and vitality.. The results of this study provide support for the use of duloxetine in the long-term management of DPNP.

Topics: Acetaminophen; Amitriptyline; Analgesics; Carbamazepine; Diabetes Complications; Diabetic Neuropathies; Diclofenac; Double-Blind Method; Duloxetine Hydrochloride; Female; Humans; Lipids; Male; Meloxicam; Middle Aged; Neuralgia; Pentoxifylline; Selective Serotonin Reuptake Inhibitors; Thiamine; Thiazines; Thiazoles; Thioctic Acid; Thiophenes; Time; Vitamin B 12

High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function.. Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined.. We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation.. This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients.

Topics: Chronic Disease; Diabetic Neuropathies; Erythropoietin; Female; Glomerulonephritis; Humans; Kidney Failure, Chronic; Male; Middle Aged; Polyneuropathies; Pyridoxal Phosphate; Pyridoxine; Recombinant Proteins; Renal Dialysis; Vitamin B 12

To investigate the effect of mecobalamin on diabetic neuropathies.. One hundred and eight patients with non-insulin dependent diabetes mellitus were involved in a randomized positive-control clinical trial. 62 cases were treated with mecobalamin 500 microg intramuscularly three times a week for four weeks then followed by 500 microg orally three times a day for additional eight weeks. 46 cases were treated with vitamin B(12) in the same way and served as controls.. Twelve weeks after the treatment, spontaneous pain and numbness of limbs were improved by 73% and 75% in the mecobalamin group, which were much higher than those in the controls (36% and 45% respectively). Hypoesthesia, hotness, coldness, oral dryness and dysuria showed better response in the mecobalamin group than in the controls (55% vs 25%, 52% vs 18%, 59% vs 30%, 53% vs 19%, 63% vs 20% respectively). Mecobalamin also benefited nerve reflection and conduction velocity to a certain extent. No obvious side effects were found.. Mecobalamin might be worthy of use as a safe agent in the treatment of diabetic neuropathies.

Topics: Administration, Oral; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Neuroprotective Agents; Vitamin B 12

Forty-five diabetes patients with painful peripheral polyneuropathy were enrolled in a 3-month observational study comparing the therapeutic efficacy of Milgamma tablets (50 mg benfothiamine and 0.25 mg cyancobalamine) with parallel randomized treatment assignment with the conventional vitamin B complex treatment regimen Neurobex. Thirty patients in group one were randomized to receive two Milgamma tablets qid for three weeks followed by 1 Milgamma tablet tid for 9 weeks. In group two 15 patients received two Neurobex tablets tid for the entire 3-month study period. Therapeutic efficacy was assessed on the basis of within-patient differences in pain severity between Milgamma and Neurobex-treated patients and in vibration perception thresholds using the Rydel-Seiffer biothesiometer at baseline and at the end of the study. Statistically significant relief of both background and peak neuropathic pain was achieved in all of the Milgamma-treated patients and vibration perception thresholds dramatically improved with a median of 1.56 measured on the biothesiometer scale (t = 3.24, P < 0.01). The sensory symptoms improvement was insignificant in the Neurobex-treated patient group and the changes in the vibration perception thresholds failed to reach statistical significance. The therapeutic efficacy of Milgamma was greater in patients with early-stage diabetes as compared with those with advanced diabetic neuropathy. No adverse reactions were observed following the administration of the medication. Our results underscore the importance of Milgamma tablets as an indispensable element in the therapeutic regimen of patients with painful diabetic polyneuropathy.

Topics: Adult; Aged; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Pain; Thiamine; Vitamin B 12; Vitamin B Complex

In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.

Topics: Administration, Oral; Aged; Capsules; Diabetic Neuropathies; Double-Blind Method; Drug Combinations; Female; Glycated Hemoglobin; Humans; Male; Median Nerve; Middle Aged; Neural Conduction; Perception; Peroneal Nerve; Pyridoxine; Sensory Thresholds; Thiamine; Time Factors; Vibration; Vitamin B 12

We studied the effect of prostaglandin E1.alpha CD (PGE1) on diabetic peripheral neuropathy by evaluating subjective symptoms and vibration sensation using a new vibrometer (SMV-5). Patients with diabetic neuropathy (n = 38) were divided into three groups; group A received no drugs (control), group B was treated with 1500 micrograms/day of oral methyl vitamin B12 (VB12) for four weeks, and group C received 1.2 micrograms/kg/day PGE1 intravenously for four weeks. There was a close relationship between symptom scores and vibratory threshold (VT). The effect of PGE1 on subjective symptoms and VT were compared with those in groups A and B. Patients who received PGE1 showed a significant improvement rate in pain and hypesthesia compared to patients in groups A and B, and in numbness compared to group A. During the study period, there was no significant change in VT in groups A and B, whereas VT was significantly improved at styloid process (P < 0.05) and at medial malleolus (P < 0.001) in group C. Our results confirmed that PGE1 significantly improved both subjective symptoms and VT, indicating that PGE1 therapy may be useful in diabetic neuropathy.

Topics: Administration, Oral; Adult; Aged; Alprostadil; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Dose-Response Relationship, Drug; Female; Humans; Hypesthesia; Injections, Intravenous; Male; Middle Aged; Pain Threshold; Vitamin B 12

We studied the clinical and neurophysiological effects of methylcobalamin on patients with diabetic neuropathy. In a double-blind study, the active group showed statistical improvement in the somatic and autonomic symptoms with regression of signs of diabetic neuropathy. Motor and sensory nerve conduction studies showed no statistical improvement after 4 months. The drug was easily tolerated by the patients and no side effects were encountered.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Muscle Contraction; Neurologic Examination; Peripheral Nerves; Reaction Time; Reflex, Stretch; Sensation; Synaptic Transmission; Vitamin B 12

In an open, multicentric observational study involving 234 doctors in private practice, the evolution of symptoms and the tolerability of a vitamin B preparation (Neurotrat forte) used as treatment in 1,149 patients with polyneuropathy, neuralgia, radiculopathy and neuritis associated with pain and paresthesias, were observed. The form of administration (ampoules, dragées), dosage and duration of treatment were left to the individual care-providing physician. The target symptoms evaluated were intensity of pain, muscle weakness affecting the legs, and paresthesia.. Under treatment, there was a clear improvement in these symptoms. At a second examination approximately three weeks after initiation of treatment, a positive effect on pain in particular was observed in 69% of the cases. Similar observations were also made for paresthesias and muscular weakness in the legs.

Topics: Diabetic Neuropathies; Drug Combinations; Female; Humans; Male; Middle Aged; Neuralgia; Neurologic Examination; Peripheral Nervous System Diseases; Pyridoxine; Thiamine; Vitamin B 12

Metformin treatment is associated with vitamin B12 deficiency, which is a risk factor for neuropathy. However, few studies have examined the relationship between metformin treatment and diabetic peripheral neuropathy (DPN), and the available findings are contradictory. We aimed to assess whether metformin treatment is associated with DPN in patients with type 2 diabetes mellitus (T2DM) in Beijing, China.. All patients with newly diagnosed T2DM between January 2010 and September 2012 in the Medical Claim Data for Employees database were included. Metformin treatment was defined as any record of metformin prescription. The average daily dose of metformin during follow-up was calculated. DPN was defined as DPN admissions occurring after a diagnosis of T2DM in the database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models.. Among 49,705 T2DM patients, 1,933 DPN events were recorded during a median follow-up of 6.36 years. The crude incidence rates were 7.12 and 3.91 per 1000 person-years for patients treated with metformin (N=37,052) versus those not treated (N=12,653). Patients treated with metformin had an 84% increased risk of DPN compared with patients not using metformin (HR, 1.84; 95% CI, 1.62, 2.10). The daily dose was positively associated with DPN risk (HR, 1.48; 95% CI, 1.46, 1.51; P for trend <0.001). The risk of DPN was 1.53-fold (1.30, 1.81) and 4.31-fold (3.76, 4.94) higher in patients with daily doses of 1.0-2.0 g and >2.0 g, respectively, than in patients who did not receive treatment. Patients aged less than 60 years had a higher risk of DPN (P<0.05 for interaction test). Among patients taking vitamin B12 at baseline, there was no increased risk of DPN in the metformin group (1.92: 0.79, 4.69).. In Chinese patients with T2DM, metformin treatment was associated with an increased risk of DPN admission and this risk responds positively to the daily dose of metformin. In particular, metformin use was a major risk factor for DPN in younger patients. Concomitant use of vitamin B12 may avoid the increased risk of DPN associated with metformin use.

Topics: Beijing; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Humans; Metformin; Middle Aged; Vitamin B 12

We will conduct a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P). The search strategies and information sources for the literature will be PubMed, Google Scholar, Web of Science and Science direct. The literature search will include studies published from inception until 30 June 2022. All included studies will be evaluated for quality and risk of bias according to the Cochrane guidelines. To investigate the stability of the results, we will conduct a sensitivity analysis of the outcomes. All data analysis will be performed using Review Manager V.5. 4.. This systematic review and meta-analysis will not require ethical approval from an institution committee as it does not have direct participants. We will obtain all our data from previous studies. The findings will be disseminated through publications in peer-reviewed journals and presented at local and international seminars and conferences.

Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Inflammation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Thioctic Acid; Vitamin B 12; Vitamins

To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circulating levels in patients with diabetic peripheral neuropathy (DPN), patients with DM type 2 (T2DM) without neuropathy, and healthy control groups.. Cross-sectional descriptive study.. Department of Internal Medicine, Namik Kemal University of Medicine, Tekirdag, Turkey, between November 2020 and February 2022.. Healthy, age, and gender matched volunteers who were admitted to the hospital for a check-up with no health problem constituted the control group (n=30). Cases diagnosed with T2DM (n=30) and those with DPN (n=30) comprised the experimental group. Stromelysin-1, calciferol, and cobalamin levels were analysed from blood samples from all groups using enzyme-linked immunosorbent assay (ELISA) with a commercial kit. Tukey's Honest Significant Difference (HSD) test was performed after one-way analysis of variance (ANOVA) for intergroup comparisons. Alpha significance level was accepted as.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Ergocalciferols; Humans; Matrix Metalloproteinase 3; Vitamin B 12; Vitamin D; Vitamins

Diabetic neuropathy is a condition that is prevalent among type 2 diabetic patients. Some physicians prescribe vitamin B12 or vitamin B complex supplements to improve symptoms, but studies have shown that there is little to no evidence of vitamin B12 being an effective treatment for diabetic neuropathy. Thus, this study aims to investigate local physicians' knowledge and tendency to prescribe vitamin B12 or vitamin B complex for the treatment or prevention of diabetic peripheral neuropathy.. It was a cross-sectional study, conducted between May and November of 2019, in several primary healthcare centers in different cities of Saudi Arabia. A total of 412 physicians with a minimum of three years of experience answered a three-part questionnaire on their demographic information, prescribing behavior, and knowledge of the relationship between vitamin B12 or vitamin B complex and diabetic neuropathy.. The study found that only 42% of the physicians believed that vitamin B12 supplementation did not prevent diabetic neuropathy, while only 52.7% found it to be an ineffective treatment for this condition. Moreover, 58.7% stated that they had certainly prescribed vitamin B12 or multivitamins as a form of treatment or prevention of diabetic neuropathy. 47.8% of the patients requested a vitamin B12 prescription 1-6 times from their physicians, while 31.6% of them requested it ≥ 7 times, with 42.5% of physicians agreeing that their prescriptions of vitamin B12 had been a result of patient demand more than clinical justification. Likewise, 43% of respondents were aware that vitamin B12 levels should be tested annually. Furthermore, a higher proportion of consultants chose not to prescribe vitamin B12 to prevent or treat diabetic neuropathy than any other rank.. The findings of this study indicate a tendency of unnecessarily prescribing vitamin B12 supplementation for the prevention or treatment of diabetic neuropathy as well as a lack of knowledge on the matter among doctors in primary care hospitals in Saudi Arabia. The study has also shown that there are patients who often request this prescription, adding pressure on their physicians to comply. Future studies should investigate most of the hospitals in Saudi cities and include less experienced residents and medical students.

Topics: Cross-Sectional Studies; Diabetes Mellitus; Diabetic Neuropathies; Humans; Perception; Physicians; Saudi Arabia; Vitamin B 12; Vitamin B Complex

Diabetic peripheral neuropathy is the most prevalent chronic complication of diabetes and is based on sensory and autonomic nerve symptoms. Generally, intensive glucose control and nerve nourishment are the main treatments. However, it is difficult to improve the symptoms for some patients; such cases are defined as refractory diabetic peripheral neuropathy (RDPN). In this paper, we present five patients treated with saline and mecobalamin by ultrasound-guided injection. The Visual Analog Scale and Toronto Clinical Scoring System were used to evaluate the symptoms, and the neuro-ultrasound scoring system and electrophysiological severity scale were evaluated by ultrasound and electrophysiological examination. In brief, ultrasound-guided hydrodissection may be a safe way to treat RDPN.

Topics: Adult; Aged; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Treatment Outcome; Ultrasonography, Interventional; Vitamin B 12

This research aimed to observe the effect of probucol combined with mecobalamin tablets on oxidative stress in patients with diabetic peripheral neuropathy (DPN).. In this prospective study, 104 patients with DPN who were treated in our hospital were included, from August 2018 to January 2020. They were divided into groups of combination (n = 52) and control (n = 52) by using a random number table. All patients took mecobalamin tablets after meals for 3 months (1 tablet/time, 3 times/d). On this basis, patients in the combination group took probucol for 3 months (4 tablets/time, 2 times/d). The observation indicators were the Toronto Clinical Scoring System (TCSS)(symptom, sensory, and reflex scores), nerve conduction velocity[sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity(MNCV) of the common peroneal nerve and median nerve], oxidative stress indicators[superoxide dismutase(SOD), malondialdehyde(MDA), glutathione peroxidase(GSH-Px) and catalase(CAT)], clinical efficacy and adverse reactions.. There was no significant difference in the symptom scores, sensory scores, reflex scores, and total scores between the two groups before treatment (p > 0.05), while these four indicators of the combination group were significantly lower than that in the control group after treatment (p < 0.05). These four indicators of the two groups after treatment were significantly lower than before treatment (p < 0.05). There was no significant difference in the SNCV and NMCV of the common peroneal nerve and median nerve between the two groups before treatment (p > 0.05), while the indicators of the combination group were significantly higher than that of the control group (p < 0.05) after treatment, and these indicators of the two groups after treatment were significantly higher than that before treatment (p < 0.05). There was no significant difference in SOD, MDA, GSH-Px, and CAT between the two groups before treatment (p > 0.05). After treatment, the SOD, GSH-Px, and CAT in the combination group were significantly higher than that in the control group (p < 0.05), while the MDA in the combination group was significantly lower than that in the control group (p < 0.05). After treatment, the SOD, GSH-Px, and CAT in the two groups were significantly higher than that before treatment (p < 0.05), while the MDA was lower (p < 0.05). The clinical efficacy of the combination group was significantly better than that of the control group (94.23 % vs 78.85 %, p＜0.05) after treatment. There was no significant difference in the incidence of total adverse reactions between the two groups (3.85 % vs 5.77 %, p > 0.05).. The therapeutic effect of probucol combined with mecobalamin tablets for patients with DPN was significant, which could effectively improve the oxidative stress response of patients and was worthy of clinical promotion.

Topics: Aged; Antioxidants; Diabetic Neuropathies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neural Conduction; Oxidative Stress; Probucol; Prospective Studies; Treatment Outcome; Vitamin B 12

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Homocysteine; Humans; Male; Metformin; Methylmalonic Acid; Middle Aged; Peripheral Nervous System Diseases; Risk Factors; Vitamin B 12

Currently, it is unclear whether the salviae miltiorrhizae (Danshen Salvia) and ligustrazine hydrochloride (Chuanxiong Chuanxiong) (SMLH) injection combined with mecobalamin can improve diabetic peripheral neuropathy (DPN). We conducted a systematic analysis to evaluate the clinical effects of SMLH injection combined with mecobalamin for treating DPN.. Seven databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wang Fang), Chinese Biomedical Literature Database (CBM), and VIP Database for Chinese Technical Periodicals (VIP) were searched for systematic literature retrieval. Each database was searched up to 2020 to identify randomized controlled trials on DPN treated with SMLH injection combined with mecobalamin. We used the RevMan 5.3 and Stata 14.0 software to assess the risk of bias in the included trials.. A total of 15 publications, including 1349 samples, were reviewed. The total effective rate of SMLH injection combined with mecobalamin was 31% higher than that of mecobalamin alone (95% confidence interval [CI] = 1.23-1.38; P < .00001). The experimental group showed a significant increase in the motor conduction velocity (MCV) of the peroneal nerve (weighted mean difference [WMD] = 4.81, 95% CI 3.53-6.09; P < .00001). In addition, SMLH injection combined with mecobalamin showed a statistical significant effect on the sensory conduction velocity (SCV) of the peroneal nerve (WMD = 5.03, 95% CI = 4.16-5.90; P < .00001), and MCV of the median nerve (WMD = 5.38, 95% CI = 4.05-6.72; P < .00001). The WMD for the change in SCV in the median nerve was 4.89 m/s (95% CI = 3.88-5.89; P < .00001). The P-values of the Egger and Begg tests were 0.967 and 0.961, respectively, indicating no publication bias. Subgroup and sensitivity analyses indicated that the results for MCV and SCV of the peroneal nerve and the median nerve were stable.. SMLH injection combined with mecobalamin can improve DPN, compared with mecobalamin alone.

Topics: Diabetic Neuropathies; Drugs, Chinese Herbal; Humans; Injections; Meta-Analysis as Topic; Neural Conduction; Phytotherapy; Pyrazines; Salvia miltiorrhiza; Systematic Review as Topic; Vitamin B 12

Although previous studies have reported the effectiveness of acupuncture combined mecobalamin (AM) in the treatment of elderly diabetic peripheral neuropathy (EDPN), no systematic study has assessed its effectiveness and safety. Thus, this study will evaluate the effectiveness and safety of AM for the treatment of patients with EDPN.. Bibliographic electronic databases will be searched as follows: Cochrane Library, PUBMED, EMBASE, CINAHL, PsycINFO, WANGFANG, and China National Knowledge Infrastructure. All of them will be searched from each database initial to March 1, 2020 without language restrictions. All study selection, information extracted, and study quality evaluation will be performed by 2 independent authors. Any disagreements between 2 authors will be resolved by a third author via discussion. RevMan 5.3 software will be used for data pooling and meta-analysis performance if it is possible.. This study will provide synthesis of current evidence of AM for patients with EDPN through primary outcome of glycemic profile, and secondary of neuropathic pain intensity, plantar tactile sensitivity, sensory nerve conduction velocity and motor nerve conduction velocity, health-related quality of life, and adverse events.. This study will provide helpful reference for the efficacy and safety of AM for the treatment of patients with EDPN to the clinicians and further studies.Study registration number: INPLASY202040094.

Topics: Acupuncture Therapy; Aged; Aged, 80 and over; Combined Modality Therapy; Diabetic Neuropathies; Dietary Supplements; Humans; Meta-Analysis as Topic; Neural Conduction; Pain Measurement; Quality of Life; Research Design; Systematic Review as Topic; Vitamin B 12

Our objective was to assess whether increased duration of metformin therapy is associated with incident peripheral neuropathy (PN) in older Veterans with diabetes.. Using national Veterans Affairs registry data from 2002 to 2015, we examined Veterans (50 + years) with diabetes. Long-term metformin therapy was defined as prescription ≥ 500 mg/day, filled for ≥ 6 consecutive months. Metformin therapy duration was examined both as continuous and categorical measures. Incident PN was defined by medical chart review. We estimated unadjusted and adjusted (variables selecteda priori)odds ratios (OR) and 95% confidence intervals (CI) using logistic regression.. The study included n = 210,004 individuals (mean ± SD: age: 66.2 ± 8.4 yrs, 96% male) prescribed metformin for 47.0 ± 34.0 months. Nineteen percent developed PN during follow-up. After adjusting for age, body mass index, duration of time receiving health care within the VA, smoking status, alcohol abuse, and vitamin B12 testing and treatment, the number of months of metformin treatment was associated with elevated odds for incident PN (aOR (metformin treatment - continuous) = 1.009 (95% CI = 1.009, 1.010); aOR (metformin treatment - categorical (ref: 6-<18 months): 18-<44.1 months = 1.57 (1.51-1.63), 44.1-<61 months = 2.05 (1.97-2.14), 61 + months = 2.69 (2.58-2.79), all p-values < 0.0001).. Our study suggests that Veterans treated for at least 18 months with metformin are approximately 2-3 times more likely to develop PN than those treated at least six, but<18 months. Future studies are needed to determine whether the association we found may be due to a decline in vitamin B12 status following metformin initiation.

Topics: Aged; Alcoholism; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Hypoglycemic Agents; Logistic Models; Male; Metformin; Middle Aged; Retrospective Studies; Risk Factors; Smoking; Time Factors; Veterans; Vitamin B 12; Vitamin B 12 Deficiency

To observe the differences in curative effects between prophylactic and therapeutic administrations of Gliclazide (GLZ) or Methylcobalamin (MCA) on diabetic peripheral neuropathy in rats.. GLZ (25 mg/kg/day) or MCA (175 μg/kg/day) was orally administrated prophylactically to streptozotocin-induced diabetic rats for 8 weeks before diabetic peripheral neuropathy developed or administrated therapeutically after diabetic peripheral neuropathy developed, respectively. The motor nerve conduction velocities (MNCV), aldose reductase (AR) activities, the polyol contents and antioxidative enzyme activities in the sciatic never tissues were determined. The morphology of sciatic never tissues was observed.. In comparison to vehicle, most of the changes in the sciatic nerves of the diabetic rats (e. g., delayed MNCV, altered/damaged nerve structure, enhanced AR activity, increased polyol contents, altered Cu, Zn-superoxide dismutase, glutathione-peroxidase activities, and elevated malondialdehyde level) were significantly ameliorated by prophylactic administration with either GLZ or MCA. In contrast, only few of above-mentioned parameters were alleviated in DPN rats by therapeutic administration with GLZ or MCA as compared to vehicle. The curative effects of GLZ or MCA prophylactic administration on MNCV, AR activity, polyol contents and antioxidative enzyme activities were markedly stronger than therapeutic administration.. Prophylactic administration of GLZ or MCA was superior to the therapeutic administration in alleviation of diabetic neuropathy in STZ-rats, suggesting that pharmacotherapy should be initiated at a much earlier stage before diabetic neuropathy developed, but not at a later stage after never damage reached.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Gliclazide; Hypoglycemic Agents; Rats; Time Factors; Vitamin B 12; Vitamin B Complex

To assess the status of vitamin B12 in patients with type 2 diabetes, and to explore any association between its deficiency and diabetic peripheral neuropathy.. This cross-sectional observational study was conducted from August, 2017, to April, 2018, at the Specialized Centre for Endocrinology and Diabetes in Baghdad, Iraq. Type 2 diabetics using metformin were subjected to clinical examination for retinopathy using fundoscopy, and peripheral neuropathy using the Michigan Neuropathy Screening Instrument. Additionally, patients were asked to fill a questionnaire and their medical records were reviewed. Blood samples were obtained for the measurement of biomarkers. Vitamin B12 deficiency was recorded at ≤187 pg/ml. Data was analysed using SPSS 25.. Of the 66 patients, 39(59%) were males and 27(41%) were females. The overall mean age was 53.3}9.2 years and the mean duration of diabetes was 104}71.8 months. The mean dose of metformin was 1135}496 mg and the duration of metformin use was 72}62 months. Overall, 19(29%) patients suffered from vitamin B12 deficiency. However, no significant difference was found between normal and deficit groups regarding the parameters that may affect vitamin B12 level. Also, no significant correlations were found between vitamin B12 concentration and the dose (p=0.16) or the duration of metformin use (p=0.09).. High prevalence of vitamin B12 deficiency was observed in metformin-treated patients with type 2 diabetes. However, the deficiency had no correlation with the rate of peripheral neuropathy.

Topics: Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Hypoglycemic Agents; Incidence; Iraq; Male; Metformin; Middle Aged; Prevalence; Vitamin B 12; Vitamin B 12 Deficiency

Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients.. 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices.. Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025).. Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

Topics: Antihypertensive Agents; Autonomic Nervous System Diseases; Cardiovascular Diseases; Cohort Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Cardiomyopathies; Diabetic Neuropathies; Female; Heart Rate; Humans; Hypertension; Hypoglycemic Agents; Male; Mass Screening; Metformin; Middle Aged; Prevalence; Proton Pump Inhibitors; Risk Factors; Vitamin B 12; Vitamin B 12 Deficiency

Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN.. The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients.. Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population.. In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Follow-Up Studies; Genotype; Homocysteine; Humans; Hypoglycemic Agents; Male; Metformin; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Mutation; Outpatients; Prognosis; Vitamin B 12

Current therapies for diabetic peripheral neuropathy with pain mask the painful symptoms while the underlying pathology continues to progress. This study assessed changes in symptoms and quality of life in patients taking a novel prescription medical food, L-methylfolate-methylcobalamin-pyridoxal-5-phosphate (LMF-MC-PP, Metanx ), intended to address the underlying metabolic needs of patients with diabetic peripheral neuropathy.. Between November 2010 and April 2012, patients rated their experiences before and after using LMF-MC-PP through an automated telephone system that included symptomatic items from the Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire and questions related to quality of life and medication satisfaction.. A total of 544 patients participated in the study. Patients reported a mean reduction of 35% in NTSS-6 scores from after 12 weeks on LMF-MC-PP. Mean (standard deviation) score was reduced by 1.5 (1.8) at 12 weeks from a baseline of 4.3 (1.5) (p < 0.05). Patients achieved significant reductions in self-reported disruptions in work/school activities, social life, and family life, respectively. Overall pain rating decreased by 32% (p < 0.05). Patients previously treated with medications reported a 52% improvement in medication satisfaction (p < 0.05).. In a real-world clinical setting, patients with diabetic peripheral neuropathy treated with LMF-MC-PP achieved significant improvements in total symptom score (NTSS-6) and in quality of life and functioning, together with greater medication satisfaction. A limitation of this study was the use of a survey instrument to collect data on patient outcomes.

Topics: Adult; Aged; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Pain; Pyridoxal Phosphate; Quality of Life; Surveys and Questionnaires; Tetrahydrofolates; Vitamin B 12

This study investigated the efficacies of gliclazide (GLZ), methylcobalamin (MCA), and GLZ+MCA combination therapy on DPN by evaluating the treatment-related changes in peripheral nerve function, the polyol pathway, and oxidative stress in the sciatic nerve of streptozotocin-induced diabetic rats.. The rat model of streptozotocin-induced diabetes was orally given GLZ (25mg/kg/day), MCA (175μg/kg/day), and GLZ+MCA (25mg/kg/day+175μg/kg/day) combination therapy for 8weeks, in order to observe its effects on the motor nerve conduction velocity (MNCV), on the activities of Na(+), K(+)-ATPase, aldose reductase(AR), AR mRNA expression, on the polyol contents, antioxidative enzyme activities and peroxidation products in the sciatic never tissue.. Most of the indicators of DPN, such as delayed MNCV, altered/damaged nerve structure, inhibited Na(+),K(+)-ATPase activity, enhanced AR activity and AR mRNA expression, increased polyol contents, altered Cu,Zn-superoxide dismutase, catalase, and glutathione-peroxidase activities, and elevated malondialdehyde level in the sciatic nerves of the diabetic rats, were significantly ameliorated by treatment with either GLZ or MCA. Moreover, the combination of GLZ and MCA was found to enhance the curative effect on DPN in parts of above-mentioned parameters as compared to monotherapy.. Monotherapy with GLZ or MCA, and especially the combined application of GLZ and MCA, could be efficient therapeutic strategies for combating experimental DPN in diabetic rats.

Topics: Animals; Blood Glucose; Diabetic Neuropathies; Drug Therapy, Combination; Gliclazide; Male; Oxidative Stress; Rats; Rats, Wistar; Sciatic Nerve; Streptozocin; Vitamin B 12

To investigate the associations of vitamin B12 (cobalamin and holotranscobalamin) status with depression, cognition and neuropathy in patients with type 2 diabetes using metformin.. In an observational study, among 550 type 2 diabetes patients using metformin, cobalamin and holotranscobalamin (holoTCII) levels were measured at the annual diabetes checkup, and deficiencies were defined as <148 and <21 pmol/L, respectively. Depression and cognitive function were assessed with corresponding International Classification of Primary Care codes and questionnaires; neuropathy with medical record data and a questionnaire. Confounding variables were retrieved from medical records. Multivariable logistic and linear regressions were used with cobalamin status as independent variable; depression, cognition and neuropathy as dependent variables.. The mean duration of diabetes was 8.4 years (±5.8); mean duration of metformin use was 64.1 months (±43.2), with a mean metformin dose of 1,306 mg/day. A sufficient cobalamin level was independently associated with a decreased risk of depression (OR 0.42; 95 % CI 0.23-0.78) and better cognitive performance (β = 1.79; 95 % CI 0.07-3.52) adjusted for confounders. This indicates that cobalamin-deficient patients had a 2.4 times higher chance of depression and a 1.79 point lower cognitive performance score. HoloTCII was not associated with any outcome.. Cobalamin deficiency was associated with an increased risk of depression and worse cognitive performance, while holoTCII was not. Screening for cobalamin deficiency may be warranted in diabetes patients using metformin. Physicians should consider a cobalamin deficiency in diabetes patients using metformin with a depression or cognitive decline.

Topics: Adult; Aged; Cognition; Depressive Disorder; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Metformin; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Diabetic Neuropathies; Humans; Peripheral Nervous System Diseases; Thioctic Acid; Vitamin B 12

The rising incidence of diabetes and its negative impact on quality of life highlights the urgent need to develop biomarkers of early nerve damage. Measurement of total vitamin B12 has some limitations. We want to determine the levels of urinary methylmalonic acid and its relationships with serum vitamin B12 and polyneuropathy. The 176 Chinese patients with Type 2 diabetes mellitus were divided into 3 groups according to the levels of vitamin B12. A gas chromatography mass spectrometric technique was used to determine blood methylmalonic acid and urinary methylmalonic acid. The diagnosis of distal diabetic polyneuropathy was based on the determination of bilateral limb sensory and motor nerve conduction velocity and amplitude with electromyogram. Multiple regression analysis revealed that urinary methylmalonic acid/creatinine, blood methylmalonic acid, and so forth were variables that influenced diabetic polyneuropathy significantly. Nerve sensory conduction velocity and nerve amplitude in the group of urinary methylmalonic acid/creatinine >3.5 mmol/mol decreased significantly. Superficial peroneal nerve sensory and motor conduction velocity and ulnar nerve compound motor active potential amplitude were inversely correlated with urinary methylmalonic acid/creatinine. Urinary methylmalonic acid correlates with serum vitamin B12 levels in person with diabetes and is a sensitive marker of early polyneuropathy.

Topics: Adult; Aged; Asian People; Biomarkers; China; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Humans; Male; Methylmalonic Acid; Middle Aged; Motor Neurons; Neural Conduction; Polyneuropathies; Prospective Studies; Sensory Receptor Cells; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Alprostadil; Diabetic Neuropathies; Humans; Peripheral Nervous System Diseases; Vitamin B 12

Topics: Diabetic Neuropathies; Humans; Peripheral Nervous System Diseases; Thioctic Acid; Vitamin B 12

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Humans; Male; Pyridoxal Phosphate; Vitamin B 12

Few modifiable risk factors are known to be associated with the presence and progression of diabetic polyneuropathy (DPN).. We have analyzed in 405 type 2 diabetic (T2DM) subjects (169 women) the association of plasma homocysteine with the presence of DPN measured with the Semmes-Weinstein (SW) monofilament test. A score below 4 was considered an altered SW monofilament test. Plasma homocysteine, vitamin B12 and folic acid were measured using standard procedures (ELISA).. Patients with T2DM with altered SW test have significantly higher age, evolution of disease, HbA1c and lower creatinine clearance values. In addition, plasma homocysteine values were independently and significantly higher in T2DM with DPN measured as altered SW test (13.64 ± 4.93 vs. 12.22 ± 4.48 μmol/l, P<.01) with similar vitamin B12 and folic acid values comparing the 2 groups.. Plasma homocysteine and HbA1c values are the 2 modifiable biological factors associated with the presence of DPN evaluated as an altered SW monofilament test in T2DM subjects.

Topics: Age Factors; Aged; Alcohol Drinking; Cardiovascular Diseases; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Progression; Female; Folic Acid; Glycated Hemoglobin; Homocysteine; Humans; Hyperhomocysteinemia; Hypesthesia; Hypoglycemic Agents; Hypolipidemic Agents; Male; Middle Aged; Overweight; Physical Examination; Risk Factors; Severity of Illness Index; Smoking; Vitamin B 12

Metanx is a product containing L-methylfolate, pyridoxal 5'-phosphate, and methylcobalamin for management of endothelial dysfunction. Metanx ingredients counteract endothelial nitric oxide synthase uncoupling and oxidative stress in vascular endothelium and peripheral nerve. This study evaluates Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes. Metanx was administered to 15-week-old ZDF and ZDF lean rats at either 4.87 mg ⋅ kg(-1) ⋅ day(-1) (a body weight-based equivalent of human dose) or 24.35 mg ⋅ kg(-1) ⋅ day(-1) by oral gavage two times a day for 4 weeks. Both doses alleviated hind limb digital sensory, but not sciatic motor, nerve conduction slowing and thermal and mechanical hypoalgesia in the absence of any reduction of hyperglycemia. Low-dose Metanx increased intraepidermal nerve fiber density but did not prevent morphometric changes in distal tibial nerve myelinated fibers. Metanx treatment counteracted endothelial nitric oxide synthase uncoupling, inducible nitric oxide synthase upregulation, and methylglyoxal-derived advanced glycation end product, nitrotyrosine, and nitrite/nitrate accumulation in the peripheral nerve. In conclusion, Metanx, at a body weight-based equivalent of human dose, increased intraepidermal nerve fiber density and improved multiple parameters of peripheral nerve function in ZDF rats. Clinical studies are needed to determine if Metanx finds use in management of diabetic peripheral neuropathy.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Disease Models, Animal; Folic Acid; Hyperalgesia; Male; Nerve Fibers; Neural Conduction; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Pyridoxal Phosphate; Rats; Rats, Zucker; Sciatic Nerve; Tibial Nerve; Tyrosine; Vitamin B 12

Metformin can result in vitamin B(12) deficiency, potentially leading to complications such as neuropathy. Annual monitoring of vitamin B(12) has been suggested; however, it is unknown whether current practice reflects this recommendation.. To identify vitamin B(12) monitoring patterns in patients on long-term, high-dose metformin. Secondary objective was to determine the frequency of new vitamin B(12) deficiency, anemia, and neuropathy documented after initiation of high-dose metformin.. Electronic medical records of veterans treated at the Veterans Affairs Maryland Healthcare System with high-dose metformin (≥2000 mg/day) as of November 1, 2010, were reviewed. Data regarding metformin treatment, vitamin B(12) measurements, and documentation of vitamin B(12) deficiency, cyanocobalamin supplementation, anemia, and neuropathy were collected. Subjects treated with metformin for less than 1 year or those with documented peripheral neuropathy, megaloblastic anemia, vitamin B(12) deficiency, or a condition associated with vitamin B(12) malabsorption prior to metformin initiation were excluded.. Subjects (N = 235) had a mean metformin dose of 2050 mg/day and mean duration of treatment of 5.2 years. Sixty percent did not have vitamin B(12) measured. Of subjects receiving metformin for 10 years or more, nearly half (46%) never had vitamin B(12) measured. New documentation of vitamin B(12) deficiency or cyanocobalamin supplementation was found in 5.5% of the population, and anemia was found in 12%. Of the 14% with new neuropathy, 42% did not have vitamin B(12) measured.. Vitamin B(12) was not routinely monitored in patients on high-dose metformin, even in those at highest risk (≥10 years of therapy), or in those with potential manifestations of vitamin B(12) deficiency (neuropathy). Cases of vitamin B(12) deficiency and resulting anemia or neuropathy may be undiagnosed and untreated because of lack of monitoring. Prospective studies examining the effect of increased vitamin B(12) monitoring on identification and treatment of vitamin B(12) deficiency in patients on metformin are warranted.

Topics: Anemia; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Monitoring; Humans; Hypoglycemic Agents; Metformin; Middle Aged; Veterans; Vitamin B 12; Vitamin B 12 Deficiency

Methyl-base-attached cobalamin (Methycobalamin) (MC) has a special affinity for nerve tissues to promote myelination and transport of axonal cytoskeleton. It is not known, however, how MC influences on peripheral nerve in experimental diabetic neuropathy.. We studied the effects of MC on expressions and activities of protein kinase C (PKC) in peripheral nerve of streptozotocin-induced diabetic rats. Wistar rats, 8 weeks of age, were rendered diabetic by streptozotocin (40 mg kg(-1), iv) and followed for 16 weeks. A half of diabetic animals were treated with MC (10 mg kg(-1) per every other day, im) after the induction of diabetes. Normal Wistar rats were served as control.. At the end, untreated diabetic animals developed significant delay of nerve conduction velocity (NCV), and MC treatment normalized the NCV. Nerve PKC activity was significantly suppressed in untreated diabetic rats, while the activity was normalized in treated animals. While PKCα located in Schwann cells, PKCβΙα and βII distributed in axoplasm, vascular walls and macrophages. The decreased PKC activity in diabetic nerve was associated with reduced expression of membrane PKCα and increased membrane expression of PKCβII, and MC treatment corrected these changes. Diabetic nerve contained an increased number of macrophages and 8-hydroxydeoxyguanosine-positive cells in the endoneurium, the latter of which was significantly suppressed by MC treatment. Elevated nerve polyol levels in diabetic nerve were partially corrected by MC treatment.. This study suggested that correction of impaired neural signalling of PKC and oxidative stress-induced damage may be a major attribute to the beneficial effects of MC on diabetic nerve.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Male; Nerve Tissue Proteins; Neural Conduction; Oxidative Stress; Protein Kinase C; Random Allocation; Rats; Rats, Wistar; Statistics as Topic; Vitamin B 12

Functional cobalamin (Cbl) deficiency (i.e., high methylmalonic acid [MMA] values despite normal serum Cbl levels) is common in the elderly and associated with neuropathy and anemia. Because diabetes is also common in the elderly and diabetic neuropathy resembles that of Cbl deficiency, the role of diabetes in functional Cbl deficiency was explored.. A retrospective review was performed of all ambulatory community-dwelling adults with normal renal function evaluated for Cbl deficiency over a 12-year period in a primary care setting. Functional Cbl deficiency was defined as MMA values >250 nmol/L with Cbl levels >400 pg/mL.. In nondiabetic subjects, MMA values varied directly with age and inversely with serum Cbl. In diabetic subjects, MMA values also increased with age but did not fall as Cbl levels increased. Thus, when Cbl levels were >400 pg/mL, mean MMA values and the incidence of functional Cbl deficiency were both significantly greater in elderly diabetic subjects (at least 70 years old) than in elderly nondiabetic subjects. Moreover, neuropathy was present in 62% of diabetic subjects with high MMA values and in only 18% of diabetic subjects with normal MMA values. Finally, pharmacologic doses of Cbl improved MMA values and neuropathy in 88 and 86% of evaluable diabetic subjects, respectively.. These observations suggest that functional Cbl deficiency is common in elderly diabetic individuals, is associated with neuropathy, and is responsive to Cbl therapy. A role for oxidative stress in the pathogenesis of functional Cbl deficiency is proposed.

Topics: Aged; Diabetes Mellitus; Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Retrospective Studies; Vitamin B 12

Agents used to treat symptoms of diabetic peripheral neuropathy (DPN) are only palliative, not disease modifying. Although studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that each of these bioavailable B vitamins may reverse the pathophysiology and symptoms of DPN, data on the efficacy of this combination therapy are limited. Therefore, we assessed the efficacy of an oral combination of L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate for improving epidermal nerve fiber density (ENFD) in the lower extremity of patients with DPN. Eleven consecutive patients with type 2 diabetes with symptomatic DPN were assessed for ENFD at the calf by means of skin punch biopsy and then placed on twice daily oral-combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate. After approximately 6 months of treatment, patients underwent follow-up biopsy. At the end of their treatment, 73% of patients showed an increase in calf ENFD, and 82% of patients experienced both reduced frequency and intensity of paresthesias and/or dysesthesias. This preliminary study suggests that combination L-methylfolate, methylcobalamin, and pyridoxal 5'-phosphate increases ENFD in patients with DPN.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Combinations; Epidermis; Female; Humans; Male; Middle Aged; Nerve Fibers; Paresthesia; Skin; Vitamin B 12

The severity of peripheral neuropathy in diabetic patients varies for unclear reasons. Long-term use of metformin is associated with malabsorption of vitamin B(12) (cobalamin [Cbl]) and elevated homocysteine (Hcy) and methylmalonic acid (MMA) levels, which may have deleterious effects on peripheral nerves. The intent of this study was to clarify the relationship among metformin exposure, levels of Cbl, Hcy, and MMA, and severity of peripheral neuropathy in diabetic patients. We hypothesized that metformin exposure would be associated with lower Cbl levels, elevated Hcy and MMA levels, and more severe peripheral neuropathy.. This was a prospective case-control study of patients with type 2 diabetes and concurrent symptomatic peripheral neuropathy, comparing those who had received >6 months of metformin therapy (n = 59) with those without metformin exposure (n = 63). Comparisons were made using clinical (Toronto Clinical Scoring System and Neuropathy Impairment Score), laboratory (serum Cbl, fasting Hcy, and fasting MMA), and electrophysiological measures (nerve conduction studies).. Metformin-treated patients had depressed Cbl levels and elevated fasting MMA and Hcy levels. Clinical and electrophysiological measures identified more severe peripheral neuropathy in these patients; the cumulative metformin dose correlated strongly with these clinical and paraclinical group differences.. Metformin exposure may be an iatrogenic cause for exacerbation of peripheral neuropathy in patients with type 2 diabetes. Interval screening for Cbl deficiency and systemic Cbl therapy should be considered upon initiation of, as well as during, metformin therapy to detect potential secondary causes of worsening peripheral neuropathy.

Topics: Aged; Case-Control Studies; Chromatography, High Pressure Liquid; Diabetic Neuropathies; Electrophysiology; Female; Homocysteine; Humans; Hypoglycemic Agents; Immunoassay; Male; Mass Spectrometry; Metformin; Methylmalonic Acid; Middle Aged; Peripheral Nervous System Diseases; Prospective Studies; Vitamin B 12

We investigated the preventive efficacy of exogenous methylcobalamin on sciatic nerve IGF-1 expression down-regulation and peripheral nerve deficit under different conditions (hyperglycemia and duration) of experimental diabetes in rats. Hyperglycemia was induced with streptozotocin, and stratified by exogenous insulin into mild and severe conditions. Duration of diabetes was ranged from 2-12 weeks. A single dose of methylcobalamin was intramuscularly administrated. Three groups of rats were compared in this study: (i) control group (NC, n = 30); (ii) saline-treated control diabetic group (n = 30); and (iii) methylcobalamin-treated diabetic group (n = 30). The study demonstrated a progressive decrease of sciatic nerve IGF-1 mRNA and peptide contents, and peripheral nerve dysfunction in the saline-treated diabetics over 12 weeks in contrast to the normal control non-diabetics (P < 0.01-0.0025). The IGF-1 reduction was delayed, which was consistent with retardation in nerve velocity conduction and structural impairment, in the methylcobalamin-treated diabetics, especially with mild hyperglycemia and shorter duration as compared with the saline-treated diabetics (P < 0.05-0.01). No effect of methylcobalamin on blood glucose was shown in the treated groups. It is concluded that exogenous methylcobalamin delayed onset of diabetic peripheral neuropathy via up-regulation of neural IGF-1 gene expression, and a better neuroprotective effect could be achieved in the presence of good control of hyperglycemia, especially at early stage of diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Gene Expression Regulation; Hyperglycemia; Insulin; Insulin-Like Growth Factor I; Male; Nerve Tissue Proteins; Neural Conduction; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sciatic Nerve; Severity of Illness Index; Time Factors; Up-Regulation; Vitamin B 12

Studies of monotherapy with L-methylfolate, methylcobalamin, or pyridoxal 5'-phosphate suggest that these B vitamins may reverse both the symptoms and the pathophysiology of diabetic peripheral neuropathy (DPN). The efficacy of oral-combination L-methylfolate, 3 mg; methylcobalamin, 2 mg; and pyridoxal 5'-phosphate, 35 mg (LMF-MC-PP) in restoring cutaneous sensitivity in patients with type 2 diabetes with DPN was evaluated in 20 type 2 diabetic patients who were given LMF-MC-PP twice daily for 4 weeks and then once daily for an additional 48 weeks. Statistically significant improvement in 1-point (tactile) and 2-point (discriminatory) static testing at the right and left great toe and heel in the patients was observed in all 3 follow-up periods: 1) baseline to 6 months, 2) baseline to 1 year, and 3) 6 months to 1 year. The greatest improvement occurred between baseline and 1 year of treatment. Treatment with oral LMF-MC-PP appears to promote restoration of lost cutaneous sensation in DPN.

Topics: Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Follow-Up Studies; Humans; Pilot Projects; Pyridoxal Phosphate; Sensory Thresholds; Tetrahydrofolates; Touch; Treatment Outcome; Vitamin B 12

Topics: Administration, Oral; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Humans; Placebos; Prodrugs; Pyridoxine; Thiamine; Time Factors; Vitamin B 12; Vitamin B 6

To observe the clinical effect of combined treatment of prostaglandin E1 and mecobalamin on diabetic peripheral neuropathy(DPN).. Seventy two patients of DPN were divided into 3 groups, they were given the drug of prostaglandin E1 (PGE1), mecobalamin, PGE1 plus mecobalamin (combined therapeutic group) and compared the therapeutic effects respectively.. The improvement of DPN symptoms and nerve conducting speeds of combined therapeutic group was obviously better than that of the single PGE1 group or mecobalamin group(P < 0.01).. Combined therapy of PGE1 and mecobalamin is better than each of single drug for improvement of DPN symptoms.

Topics: Adult; Aged; Alprostadil; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Vitamin B 12

Limited data are available on determinants of diabetic neuropathy as its pathogenesis is multifactorial. Since homocysteine exhibits toxic effects on vascular endothelial cells, the association between homocysteine and the prevalence of neuropathy in Type 2 diabetes mellitus was investigated.. A total of 65 Type 2 diabetic patients were consecutively enrolled into the study. Neuropathy was diagnosed according to clinical symptoms, clinical examination, electrophysiological sensory testing and autonomic function testing. With regard to homocysteine-related parameters, plasma homocysteine, folate, vitamin B12, vitamin B6 and renal function (creatinine, ceratinine clearance, cystatin C) were measured, and the C677T polymorphism of the methylenetetrahydrofolate reductase gene was determined.. Forty-three of the Type 2 diabetic patients were classified as suffering from neuropathy. Both patient groups were comparable with regard to demographic data, blood pressure, glucose metabolism, renal function and homocysteine-related vitamins. In contrast, homocysteine levels (P = 0.04) and the frequency of hyperhomocysteinemia (>or= 15 micromol/l) (P = 0.01) were significantly increased in neuropathic patients. In a logistic regression model with neuropathy as dependent variable, homocysteine (adjusted for creatinine, homocysteine-related vitamins, HbA1c and duration of diabetes) was the only significant variable associated with the prevalence of neuropathy (odds ratio for homocysteine per 5 micromol/l increase: 2.60 (95% confidence interval 1.07-6.33)).. The data indicate that homocysteine is independently associated with the prevalence of diabetic neuropathy in a collective of Type 2 diabetic patients. A larger, prospective study would be desirable to clarify the role of homocysteine in the pathogenesis of diabetic neuropathy.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Blood Pressure; Creatinine; Cystatin C; Cystatins; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Glomerular Filtration Rate; Homocysteine; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxidoreductases Acting on CH-NH Group Donors; Polymorphism, Genetic; Pyridoxine; Vitamin B 12

To study the effects of the intravenous administration of methylcobalamin, an analogue of vitamin B12, for uremic or uremic-diabetic polyneuropathy in patients who are receiving maintenance hemodialysis. An ultra-high dose of vitamin B12 has been reported to promote peripheral nerve regeneration in experimental neuropathy.. Nine patients received a 500 microg methylcobalamin injection 3 times a week for 6 months. The effects were evaluated using neuropathic pain grading and a nerve conduction study.. Serum concentrations of vitamin B12 were ultra-high during treatment due to the lack of urinary excretion. After 6 months of treatment, the patients' pain or paresthesia had lessened, and the ulnar motor and median sensory nerve conduction velocities showed significant improvement. There were no side effects.. Intravenous methycobalamin treatment is a safe and potentially beneficial therapy for neuropathy in chronic hemodialysis patients.

Topics: Action Potentials; Aged; Chronic Disease; Diabetic Neuropathies; Female; Follow-Up Studies; Humans; Injections, Intravenous; Male; Middle Aged; Neural Conduction; Pain Measurement; Peripheral Nervous System Diseases; Renal Dialysis; Severity of Illness Index; Treatment Outcome; Uremia; Vitamin B 12

Topics: Adult; Antidepressive Agents, Tricyclic; Diabetic Neuropathies; Drug Therapy, Combination; Hematinics; Humans; Lofepramine; Male; Middle Aged; Phenylalanine; Vitamin B 12

This study was undertaken to examine the effects of aldose reductase inhibitor (ARI) and vitamin B12 (VB12) on myocardial uptake of iodine-123 metaiodobenzylguanidine (MIBG) in patients with diabetic autonomic disorder. Myocardial scintigraphy using 123I-MIBG was performed on 20 healthy volunteers (controls) and 56 patients with non-insulin-dependent diabetes mellitus (NIDDM), in order to obtain the heart/mediastinum ratio in the initial (HMi) and the delayed images (HMd), and the washout rate (%WR). Thirty-four of the 56 NIDDM patients could be diagnosed as having diabetic autonomic disorder by evaluating their scintigraphic findings in comparison with the controls. Seventeen of these 34 patients received 150 mg/day of doses before meals, and the other 17 received 1.5 mg/day of mecobalamin (VB12 group) in three divided doses after meals, for 3-5 months. According to the presence or absence of clinical symptoms of autonomic or peripheral somatic nerve disorder, the patients were subclassified into four groups. group 1=patients, with autonomic symptoms or somatosensory disorder in the ARI group; group 2=patients without autonomic symptoms or somatosensory disorder in the ARI group; group 3=patients with autonomic symptoms or somatosensory disorder in the VB12 group; and group 4=patients without autonomic symptoms or somatosensory disorder in the VB12 group. After completion of the treatment, myocardial scintigraphy was performed again. Comparing the results obtained before and after the treatment, it was seen that ARI improved only the HMi in group 1 (P=0.046), whereas VB12 significantly improved HMi in the group 3 (P=0.018) and HMi, HMd and %WR in group 4 (P=0.043, P=0.018 and P=0.043, respectively). We conclude that VB12 is more efficacious than ARI in the treatment of diabetic cardiovascular autonomic disorder.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Aged, 80 and over; Aldehyde Reductase; Autonomic Nervous System Diseases; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Enzyme Inhibitors; Female; Heart; Heart Diseases; Humans; Male; Middle Aged; Radionuclide Imaging; Radiopharmaceuticals; Rhodanine; Thiazolidines; Vitamin B 12

Topics: Adult; Aged; Autonomic Nervous System Diseases; Diabetic Neuropathies; Heart Rate; Humans; Middle Aged; Signal Processing, Computer-Assisted; Vitamin B 12

The present study was aimed to determine the vitamin status of vitamins A, E, beta-carotene, B1, B2, B6, B12 and folate in plasma using HPLC and vitamins B1, B2 and B6 in erythrocytes using the apoenzyme stimulation test with the Cobas-Bio analyzer in 29 elderly type II diabetic women with (G1: n = 17, age: 68.6 +/- 3.2 years) and without (G2: n = 12, age: 71.8 +/- 2.7 years) diabetic polyneuropathy. The basic parameters as age, hemoglobin A1c, fructosamine and duration of the disease did not differ in both groups. Furthermore, retinopathy was assessed with fundoscopy and nephropathy with creatinine clearance. The creatinine clearance (G1: 50.6 +/- 3.4 vs. G2: 63.6 +/- 3.7 ml/min, 2p < 0.025) and the percentage of retinopathy (G1: 76.5% vs. G2: 16.7%, 2p = 0.002) were different indicating that G1 had significantly more severe late complications than G2. Current plasma levels of all measured vitamins (A, E, beta-carotene, B1, B2, B6, B12 and folate) and the status of B1, B2 and B6 in erythrocytes did not vary between the two groups (2p > 0.1). In summary, we found a lack of association between the actual vitamin condition in plasma and erythrocytes and diabetic neuropathy.

Topics: Aged; Avitaminosis; beta Carotene; Carotenoids; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Female; Folic Acid; Glycated Hemoglobin; Humans; Male; Middle Aged; Neurologic Examination; Pyridoxine; Riboflavin; Thiamine; Vitamin A; Vitamin B 12; Vitamin E; Vitamins

Topics: Animals; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Humans; Nerve Degeneration; Rats; Vitamin B 12

Topics: Alprostadil; Anticonvulsants; Antidepressive Agents, Tricyclic; Child; Diabetic Neuropathies; Female; Humans; Hyperglycemia; Male; Mexiletine; Pain; Pain Management; Polymers; Sensation; Sodium-Potassium-Exchanging ATPase; Vitamin B 12

Topics: Alprostadil; Diabetic Neuropathies; Electromyography; Humans; Insulin; Neural Conduction; Neurologic Examination; Vitamin B 12

Topics: Administration, Oral; Antidepressive Agents, Tricyclic; Contraindications; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Drug Interactions; Humans; Hypoglycemic Agents; Hypotension, Orthostatic; Injections, Subcutaneous; Insulin; Vitamin B 12

Topics: Diabetic Neuropathies; Evoked Potentials, Auditory; Humans; Mexiletine; Vitamin B 12

Seven men and four women with symptomatic diabetic neuropathy were treated with methylcobalamin (2,500 micrograms in 10 ml of saline) injected intrathecally. Treatment was begun when patients had good metabolic control, as determined by measurements of plasma glucose and hemoglobin, and was repeated several times with a one-month interval between injections. Three patients were re-treated one year after the last intrathecal injection. Symptoms in the legs, such as paresthesia, burning pains, and heaviness, dramatically improved. The effect appeared within a few hours to one week and lasted from several months to four years. The mean peroneal motor-nerve conduction velocity did not change significantly. The mean (+/- SD) concentration of methylcobalamin in spinal fluid was 114 +/- 32 pg/ml before intrathecal injection (n = 5) and 4,752 +/- 2,504 pg/ml one month after intrathecal methylcobalamin treatment (n = 11). Methylcobalamin caused no side effects with respect to subjective symptoms or characteristics of spinal fluid. These findings suggest that a high concentration of methylcobalamin in spinal fluid is highly effective and safe for treating the symptoms of diabetic neuropathy.

Topics: Adult; Aged; Diabetic Neuropathies; Female; Humans; Injections, Spinal; Male; Middle Aged; Neural Conduction; Vitamin B 12

Topics: Animals; Diabetic Neuropathies; Humans; Male; Rats; Vitamin B 12; Vitamin B 12 Deficiency

The catalysis by phosphatidylethanolamine methyltransferase (PEMT) of phosphatidylcholine (PC) synthesis by the successive methylation of phosphatidylethanolamine in the presence of S-adenosylmethionine (AdoMet) as methyl donor, was detected in actively myelinating mouse brains. PEMT activity in the microsome fraction of fetal mouse brain at 17 days of gestation was 253 mu u/mg protein and that of adult brain after 7 days of remyelination following 6 weeks cuprizone administration was 148 mu u/mg. These figures are much higher than found in normal adult brains (1.7 mu u/mg). An increase in PEMT activity was observed in the brains of genetically transmitted diabetic mice, C57BL/KsJ-db/db, and streptozotocin-induced diabetic mice; 16.3 and 9.2 mu u/mg, respectively. The methyl group of mecobalamin was transferred to homocysteine producing AdoMet and was further metabolized into choline and acetylcholine in brain slices. These results suggest that in the diabetic state, an increase in PC synthesis is probably required in order to replace damaged myelin or to supply choline or acetylcholine essential to for nerve functions. Mecobalamin might serve as the source of the methyl group utilized for PC synthesis.

Topics: Animals; Brain; Cuprizone; Demyelinating Diseases; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Humans; Methyltransferases; Mice; Mice, Inbred C57BL; Phosphatidylethanolamine N-Methyltransferase; Vitamin B 12

Topics: Adult; Aged; Diabetic Neuropathies; Humans; Methionine; Middle Aged; Nervous System Diseases; Neuritis; Peripheral Nervous System Diseases; Physical Therapy Modalities; Polyneuropathies; Thioctic Acid; Transketolase; Vitamin B 12

To study in vivo effect of methylcobalamin (CH3-B12) on the peripheral nerve structures, rats with experimental diabetes induced by streptozotocin were administered with daily intramuscular injection of CH3-B12 (500 microgram/kg) for 16 weeks. By isolated nerve fiber studies, CH3-B12-treated diabetic rats showed less incidence of paranodal demyelination as an early sign of segmental demyelination than non-treated diabetic rats. From morphometrical analysis on sural nerves, the reduction in the density of myelinated nerve fibers, nerve fiber size and axon size of myelinated fibers was definitely protected in treated diabetic rats. The results suggested that continuous treatment with CH3-B12 had an ameliorative effect on the peripheral nerve lesions in experimental diabetic neuropathy.

Topics: Animals; Axons; Diabetes Mellitus, Experimental; Diabetic Neuropathies; Male; Nerve Fibers, Myelinated; Peripheral Nerves; Rats; Rats, Inbred Strains; Spinal Nerves; Streptozocin; Vitamin B 12

Investigations on the vitamin pattern of diabetic neuropathy: thiamine, riboflavin, pyridoxine, cobalamin and tocopherol. The contents of the vitamins mentioned above have been measured in the blood of 119 patients (53 diabetic neuropathies, 66 diabetics without neuropathy). The incidence of neuropathy shows a strong correlation with the duration of the diabetic state, but not with sex, nor with concomitant diseases such as adipositas, hypertension, heart and circulatory diseases, except retinopathia diabetica. Most of the diabetics in our study are well supplied with vitamins B1, B2, and E; B6 and B12 are occasionally low, but there is no statistically relevant difference between diabetic controls and neuropathies. Adipose patients have neither a markedly different vitamin content nor a different calory uptake from non-adipose patients. A general trend towards reduced total calory uptake is seen in old age, men (lower protein intake) and women (lower carbohydrate intake) obviously differing somewhat in their habits. The influence of therapy on the vitamin pattern is not clear cut, except for patients under diet and biguanide-therapy showing a higher proportion of low or subnormal B12 values. The increased frequency of neuropathies in patients treated with sulfonyl-urea approaches only the limits of significance and needs further investigations.

Topics: Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Male; Middle Aged; Obesity; Pyridoxine; Riboflavin; Sex Factors; Thiamine; Vitamin B 12; Vitamin E

In most cases of diabetic neuropathy, demyelinization processes on the nerve lead to considerable decreases in the nerve conduction velocity. It has up to now been possible to substantiate the therapeutic success of neurotropic vitamins only by more or less subjective parameters obtained from numerous studies. In the present investigation of 33 diabetics with polyneuropathies it was possible to show that the nerve conduction velocity is a parameter which can be measured objectively for the monitoring of the development of neuropathies. The increases in the nerve conduction velocity, which had decreased prior to the beginning of treatment, coincided closely with clinical evaluations. The therapeutic use of Neurobion was assessed on the basis of this criterion. The dosage plan for hospitalized patients differed from that for outpatients. In the case of inpatients who received high doses of vitamins, it was possible to substantiate the effect of Neurobion significantly in statistical terms by means of the corresponding increases in the nerve conduction velocity. There were different therapeutic results in both groups of patients. The outpatients receiving smaller single doses as well as a smaller total dose of Neurobion could not be treated as successfully as the inpatient. This dose effect that is apparent must be substantiated by further investigations in this area.

Topics: Diabetic Neuropathies; Female; Humans; Male; Middle Aged; Neural Conduction; Pyridoxine; Thiamine; Vitamin B 12; Vitamin B Complex

Topics: Adult; Diabetic Neuropathies; Electromyography; Humans; Vitamin B 12

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Aged; Anti-Bacterial Agents; Arteriosclerosis; Basilar Artery; Cerebrovascular Disorders; Chronic Disease; Deoxyribonucleases; Diabetic Neuropathies; Diuretics; Facial Nerve; Facial Paralysis; Female; Herpes Zoster; Humans; Hypertension; Ischemia; Male; Middle Aged; Physical Therapy Modalities; Prednisolone; Recurrence; Tonsillitis; Vertebral Artery; Vitamin B 12

Topics: Adolescent; Adult; Diabetic Neuropathies; Female; Humans; Leprosy; Male; Middle Aged; Pellagra; Peripheral Nervous System Diseases; Polyradiculopathy; Vitamin B 12

Topics: Adolescent; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Humans; Vitamin B 12

Topics: Aged; Diabetic Neuropathies; Humans; Male; Middle Aged; Ophthalmoplegia; Vitamin B 12

Topics: Anemia, Pernicious; Diabetic Neuropathies; Humans; Mental Disorders; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Adult; Child; Child, Preschool; Diabetic Neuropathies; Female; Humans; Infant; Male; Middle Aged; Prognosis; Vitamin B 12

Topics: Diabetes Mellitus; Diabetic Neuropathies; Drug Therapy; Hematinics; Humans; Pathology; Peripheral Nervous System Diseases; Thiamine; Vitamin B 12

Topics: Adenine Nucleotides; Adenosine Monophosphate; Blood Proteins; Cholesterol; Diabetic Neuropathies; Glycoproteins; Glycosuria; Humans; Hypoglycemic Agents; Lipids; Lipoproteins; Neuritis; Pyruvates; Thiamine; Vitamin B 12

Topics: Diabetic Neuropathies; Diagnosis; Liver Extracts; Pantothenic Acid; Pathology; Physiology; Procaine; Statistics as Topic; Thiamine; Thioctic Acid; Vitamin A; Vitamin B 12; Vitamin B Complex; Vitamins

Topics: Absorption; Biopsy; Celiac Disease; Cobalt Isotopes; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Diagnosis, Differential; Feces; Humans; Intestine, Small; Intestines; Iodine Isotopes; Lipid Metabolism; Pathology; Steatorrhea; Triolein; Vitamin B 12

Topics: Anemia; Anemia, Macrocytic; Anemia, Pernicious; Diabetic Neuropathies; Hematinics; Humans; Hydrogen Cyanide; Hydroxocobalamin; Neuritis; Vitamin B 12; Vitamin B Complex

Topics: Absorption; Achlorhydria; Adolescent; Child; Cobalt Isotopes; Corrinoids; Diabetes Mellitus; Diabetic Neuropathies; Humans; Liver; Metabolism; Radioactivity; Radioisotopes; Radionuclide Imaging; Research; Vitamin B 12

Topics: Diabetes Mellitus; Diabetic Neuropathies; Geriatrics; Hepatitis; Hepatitis A; Humans; Hydroxocobalamin; Liver Cirrhosis; Neuralgia; Thiamine; Vitamin B 12

Topics: Corrinoids; Diabetes Complications; Diabetic Neuropathies; Disease; Hematinics; Peripheral Nerves; Vitamin B 12

Topics: Adenosine Triphosphate; Diabetes Complications; Diabetic Neuropathies; Humans; Liver Extracts; Nervous System Diseases; Pantothenic Acid; Thiamine; Vitamin B 12; Vitamin B Complex