Objective: To evaluate the efficacy of oral mixed tocotrienols for patients with diabetic peripheral neuropathy.
Design, Setting, and Participants: The Vitamin E in Neuroprotection Study (VENUS) was a parallel, double-blind, placebo-controlled trial that recruited participants from January 30, 2011, to December 7, 2014, with 12 months of follow-up. This trial screened 14 289 patients with diabetes from 6 health clinics and ambulatory care units from 5 public hospitals in Malaysia. A total of 391 patients who reported neuropathic symptoms were further assessed with Total Symptom Score (TSS) and Neuropathy Impairment Score (NIS). Patients 20 years or older with a TSS of 3 or higher and an NIS of 2 or higher were recruited.
Interventions: Patients were randomized to receive 200 mg of mixed tocotrienols twice daily or matching placebo for 12 months. Patients with hyperhomocysteinemia (homocysteine level ≥2.03 mg/L) received oral folic acid, 5 mg once daily, and methylcobalamin, 500 μg thrice daily, in both groups.
Main Outcomes and Measures: The primary outcome was patient-reported neuropathy TSS (lancinating pain, burning pain, paresthesia, and asleep numbness) changes at 12 months. The secondary outcomes were NIS and sensory nerve conduction test result.
Results: Of 391 eligible patients, 300 were recruited (130 [43.3%] male; mean [SD] age, 57.6 [8.9] years; mean [SD] duration of diabetes, 11.4 [7.8] years) and 229 (76.3%) completed the trial. The TSS changes between the tocotrienols and placebo groups at 12 months (-0.30; 95% CI, -1.16 to 0.56; P = .49) were similar. No significant differences in NIS (0.60; 95% CI, -1.37 to 2.65; P = .53) and sensory nerve conduction test assessments were found between both groups. In post hoc subgroup analyses, tocotrienols reduced lancinating pain among patients with hemoglobin A1C levels greater than 8% (P = .03) and normohomocysteinemia (homocysteine level <2.03 mg/L; P = .008) at 1 year. Serious adverse events in both groups were similar, except more infections were observed in the tocotrienols group (6.7% vs 0.7%, P = .04). Results reported were of modified intention-to-treat analyses.
Conclusions and Relevance: Supplementation of oral mixed tocotrienols, 400 mg/d for 1 year, did not improve overall neuropathic symptoms. The preliminary observations on lancinating pain among subsets of patients require further exploration.
Trial Registration: National Medical Research Registry Identifier: NMRR-10-948-7327 and clinicaltrials.gov Identifier: NCT01973400.
METHOD: In this study, the MNSI data were collected from the Epidemiology of Diabetes Interventions and Complications (EDIC) clinical trials. Two different datasets with different MNSI variable combinations based on the results from the eXtreme Gradient Boosting feature ranking technique were used to analyze the performance of eight different conventional ML algorithms.
RESULTS: The random forest (RF) classifier outperformed other ML models for both datasets. However, all ML models showed almost perfect reliability based on Kappa statistics and a high correlation between the predicted output and actual class of the EDIC patients when all six MNSI variables were considered as inputs.
CONCLUSIONS: This study suggests that the RF algorithm-based classifier using all MNSI variables can help to predict the DSPN severity which will help to enhance the medical facilities for diabetic patients.
AIMS: This study intended to assess the association of peripheral neuropathy with statins therapy amongst Type 2 diabetic patients.
METHODS: At Penang General Hospital, 757 cases were categorized into two groups (564 with statins therapy and 193 without statins therapy). The diagnosis of PN was investigated retrospectively for a period of 10 years (2006-2016). Confounding risk factors as age, diabetes period, hypertension, glycemic control, other co-morbidity, and prescriptions were matched.
RESULTS: About 129 (22.9%) cases from 564 statins users had PN. Only 30 (15.5%) subjects had PN from 193 statins non-users. Chi-square test showed a significant variance among statins treatment cohort and statin-free cohort in the occurrence of PN (P-value: 0.001). Spearman's investigation presented a positive correlation (r: 0.078, p-value: 0.031) among statins use and PN prevalence. Binary logistic regression was statistically significant for statins therapy as a predictor of peripheral neuropathy incidence (r2: 0.006, p-value: 0.027) amid diabetic patients. The relative risk of peripheral neuropathy connected with statins therapy is (RR: 1.47, 95% CI: 1.02-2.11). The excess relative risk is 47.1%. While the absolute risk (AR) is 7.3% and the number needed to harm (NNH) is 14.
CONCLUSIONS: The study indicated a positive association between peripheral neuropathy and statins utilization. Peripheral neuropathy was higher amongst statins users than the statins-free group.
FUNDING: Pfizer.