Explore the vast range of titles available.

In a secondary analysis comparing the effect of insulin glargine, glimepiride, liraglutide, and sitagliptin, added to metformin, on the incidences of microvascular complications and death, no material between-group differences were seen.

OBJECTIVE: We aimed to determine the corneal confocal microscopy (CCM) parameter that best identifies diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes and to describe its performance characteristics. RESEARCH DESIGN AND METHODS: Concurrent with clinical and electrophysiological examination for classification of DSP, CCM was performed on 89 type 1 diabetic and 64 healthy subjects to determine corneal nerve fiber length (CNFL), density, tortuosity, and branch density. Area under the curve (AUC) and optimal thresholds for DSP identification in those with diabetes were determined by receiver operating characteristic (ROC) curve analysis. RESULTS: DSP was present in 33 (37%) subjects. With the exception of tortuosity, CCM parameters were significantly lower in DSP case subjects. In ROC curve analysis, AUC was greatest for CNFL (0.88) compared with fiber density (0.84, P = 0.0001), branch density (0.73, P < 0.0001), and tortuosity (0.55, P < 0.0001). The threshold value that optimized sensitivity and specificity for ruling in DSP was a CNFL of ≤14.0 mm/mm2 (sensitivity 85%, specificity 84%), associated with positive and negative likelihood ratios of 5.3 and 0.18. An alternate approach that used separate threshold values maximized sensitivity (threshold value ≥15.8 mm/mm2, sensitivity 91%, negative likelihood ratio 0.16) and specificity (≤11.5 mm/mm2, specificity 93%, positive likelihood ratio 8.5). CONCLUSIONS: Among CCM parameters, CNFL best discriminated DSP cases from control subjects. A single threshold offers clinically acceptable operating characteristics, although a strategy that uses separate thresholds to respectively rule in and rule out DSP has excellent performance while minimizing unclassified subjects. We hypothesize that values between these thresholds indicate incipient nerve injury that represents those individuals at future neuropathy risk.

This randomized controlled study used corneal confocal microscopy (CCM) to compare the efficacy of Mecobalamin intramuscular injections vs oral tablets in treating mild to moderate diabetic peripheral neuropathy (DPN) by detecting early nerve fiber repair. Enrolled patients were randomized approximately 1:1 to receive Mecobalamin intramuscular injections (0.5 mg/day, 3 times/week) or Mecobalamin oral tablets (1.5 mg/day) for 8 weeks. Primary outcome was change of inferior whorl length (IWL) from baseline. Secondary outcomes included changes of corneal nerve fibre length (CNFL), corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and the Survey of Autonomic Symptoms (SAS). 15 (93.75%) patients in the injection group and 17 (89.47%) patients in the tablet group completed the study. The injection treatment significantly improved patients’ IWL from baseline (21.64 ± 3.00 mm/mm 2 vs 17.64 ± 4.83 mm/mm 2 , P  < 0.01) while the tablet treatment didn’t. Additionally, the injection treatment led to significantly improved CNFL, CNBD and SAS from baseline (all P  < 0.05) while the tablet treatment did not. No patient experienced any adverse events. In conclusion, CCM is sensitive enough to detect the superior efficacy of 8-week Mecobalamin intramuscular injection treatment for DPN compared to the oral tablet treatment. ClinicalTrials.gov registration number: NCT04372316 (30/04/2020).

Aims/hypothesis There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial. Methods One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n  = 910; RC, n  = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN. Results At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care. Conclusions/interpretation In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.

Aims/Introduction Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN. Materials and Methods Standardized CARTs (R‐R response to paced breathing, Valsalva, postural changes) and digitized 12‐lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R‐R intervals (SDNN) and the root mean square of successive differences between normal‐to‐normal R‐R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG‐derived CAN and CARTs‐defined CAN. Results Participants with CARTs‐defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P < 0.001). The optimal cut‐off points of ECG‐derived CAN were <17.13 and <24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30–0.51) for the optimal cut‐off point, showing fair agreement with CARTs‐defined CAN. Combining SDNN and rMSSD optimal cut‐off points does not provide additional predictive power for CAN. Conclusions These analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care. Participants with cardiovascular reflex tests‐defined cardiovascular autonomic neuropathy (CAN) had significantly lower standard deviation of normally conducted R‐R intervals and root mean square of successive differences between normal‐to‐normal R‐R intervals compared to those without CAN (P < 0.001). standard deviation of normally conducted R‐R intervals plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistics for standard deviation of normally conducted R‐R intervals was 0.41 (95% confidence interval 0.30–0.51) for the optimal cut‐off point, showing fair agreement with cardiovascular reflex tests‐defined CAN.

Objective: The objective of this study is to evaluate and compare the effectiveness of treatments with two different electrical stimulation (e‐stim) devices—pulsed direct current (DC) (Neubie) and alternating current (AC) (transcutaneous electrical stimulation (TENS))—in the treatment of symptoms for patients with diabetic peripheral neuropathy (DPN). Design: Randomized controlled trial (RCT) with parallel groups. Methods: One hundred fifty participants were recruited from 13 Hands‐On Diagnostics–affiliated sites across several US locations. Participants were randomly divided into two groups for comparison—Neubie and TENS. Participants received a 30‐min foot stimulation protocol with either TENS unit electrodes or Neubie electrodes. Outcome measures included the Toronto Clinical Neuropathy Score (TCNS), two‐point discrimination, visual analogue scale (VAS), vibration sense (VBS), nerve conduction velocity (NCV), and nerve amplitude. The effect of the two variables on all outcome measures was determined using an analysis of covariance (ANCOVA). Results: The Neubie group demonstrated statistically significant improvements in TCNS for both right and left sides ( p < 0.001), two‐point discrimination of the dominant foot ( p = 0.001), VBS ( p = 0.022) and VAS scores ( p = 0.009), and some but not all nerves tested by NCV ( p < 0.05). Conclusion: Overall, DPN treatment with the Neubie resulted in significant improvements in several major outcome measures, whereas TENS showed no significant difference in any outcome measure. These findings support the use of DC devices as a potentially superior therapeutic treatment for neuropathy over AC devices like the TENS unit. Trial Registration: ClinicalTrials.gov identifier: NCT05442021

Peripheral neuropathy is a leading cause of morbidity and increased mortality among diabetic patients. It is characterized by significant deficits in vibration and tactile sensation. With an annual incidence of 2%, it affects as many as 110 million people worldwide. The aim of this study was to assess factors associated with peripheral neuropathy among diabetic patients in chronic care clinic in Gamo and Gofa zone, South Ethiopia. An institution- based unmatched case control study was employed among 528 randomly selected participants using a pre-tested, interviewer-administered, and structured questionnaire. Bivariate and multivariable logistic regression analysis was conducted to identifiy determinants of peripheral neuropathy using IBM SPSS version 25. The odds of being an urban dweller was 2.67 times higher among cases than controls [AOR = 2.67 (1.27, 5.63)]. The likelihood of fasting blood glucose level between 203 and 282 and 282 and above was 2.55 and 3.88 times higher among cases than controls [AOR = 2.55 (1.91, 7.16)] and [AOR = 3.88 (1.42, 10.60)] respectively. The probability of living with diabetes mellitus for 10 and more years was 3.88 times higher among cases than controls [AOR = 3.88 (1.42, 10.60)]. The odds of controlling glucose level after developing symptom was 5.33 times higher among cases than controls [AOR = 5.33 (1.28, 12.24)]. The probability of having high blood pressure was 2.36 times higher among cases than controls [AOR = 2.36 (1.26, 4.43)]. The likelihood of having a family history of complication from diabetes mellitus was 5.60 times higher among cases than controls [AOR = 5.60 (2.03, 15.43)]. The odds of exercising 3 times per week for 15 to 30 minutes and for less than 15 minutes were 2.96 and 4.92 times higher among cases than controls respectively [AOR = 2.96 (1.32, 6.61)] and AOR = 4.92, 95% CI (1.85, 13.04) respectively. The likelihood of having a waist circumference greater than or equal to 40 inch was 2.72 times higher among cases than controls [AOR = 2.72 (1.07, 6.94)]. This study showed that residence, duration of diabetic mellitus, family history of complication from diabetic mellitus, level of fasting blood glucose, method of glycemic control, having a high blood pressure/hypertension/, frequency and duration of physical activity and waist circumference were found to be determinants of peripheral neuropathy. Thus, the concerned health authorities and health professionals should target on these factors in their efforts to prevent peripheral neuropathy among diabetics in the study area.

Objective To evaluate the effect of 8-week moderate intensity aerobic (heart-rate reserve 40–60 %) exercise on neuropathy quality of life in type 2 diabetes. Methods A single blind, parallel-group, randomized controlled trial was carried out in a tertiary setting. People with type 2 diabetes were eligible for the study if they had clinical neuropathy which was defined by a minimum score of seven on the Michigan diabetic neuropathy score. Following which, the patients were randomly assigned to an 8-week program by a computer-generated random number tables to intervention or control group. Repeated measure analysis of variance was used for data analysis (p < 0.05 was considered significant). Results There were 47 participants in the control group and 40 participants in the study group after randomization but 37 from the control group and 29 from the intervention group completed the final analysis. The two groups had a significant difference, pre–post intervention in scores of pain (F = 7, p = 0.01), sensory symptoms (F = 4.60, p = 0.04), restricted activities of daily living (F = 4.97, p = 0.03), disruptions in social relationships (F = 5.43, p = 0.02), specific impact on quality of life (F = 9.28, p < 0.001) overall quality of life (F = 28.72, p < 0.001), and total score (F = 31.10, p < 0.001). Degrees of freedom for all the components were 1, 62. Conclusion Moderate intensity aerobic exercise is cornerstone in improving the quality of life of individuals with peripheral neuropathy in type 2 diabetes.

Diabetes is the most important cause of peripheral neuropathy (DPN). No definitive treatment for DPN has been established, and very few data on the role of exercise training on DPN have been reported. We sought to examine the effects of long-term exercise training on the development of DPN in both Types 1 and 2 diabetic patients. Seventy-eight diabetic patients without signs and symptoms of peripheral DPN were enrolled, randomized, and subdivided in two groups: 31 diabetic participants [15 f, 16 m; 49±15.5 years old; body mass index (BMI)=27.9±4.7], who performed a prescribed and supervised 4 h/week brisk walking on a treadmill at 50% to 85% of the heart rate reserve (exercise group: EXE), and a control group of 47 diabetic participants (CON; 24 f, 23 m; 52.9±13.4 years old; BMI=30.9±8.4). Vibration perception threshold (VPT), nerve distal latency (DL), nerve conduction velocity (NCV), and nerve action potential amplitude (NAPA) in the lower limbs were measured. We found significant differences on Δ (delta) in NCV for both peroneal and sural motor nerve between the EXE and CON groups during the study period ( P<.001, for both). The percentage of diabetic patients that developed motor neuropathy and sensory neuropathy during the 4 years of the study was significantly higher in the CON than the EXE group (17% vs. 0.0%, P<.05, and 29.8% vs. 6.45%, P<.05, respectively). In addition, the percentage of diabetic patients who developed increased VPT (25 V) during the study was significantly higher in the CON than the EXE group (21.3% vs. 12.9%, P<.05). Change on Hallux VPT from baseline to the end of the study was significantly different between the EXE and CON groups ( P<.05); no significant change in Malleolus VPT between the two groups occurred. This study suggests, for the first time, that long-term aerobic exercise training can prevent the onset or modify the natural history of DPN.

To determine whether duloxetine is noninferior to (as good as) pregabalin in the treatment of pain associated with diabetic peripheral neuropathy. We performed a 12-week, open-label study of patients with diabetic peripheral neuropathic pain who had been treated with gabapentin (≥900 mg/d) and had an inadequate response (defined as a daily pain score of ≥4 on a numerical rating scale [0-10 points]). The first patient was enrolled on September 28, 2006, and the last patient visit occurred on August 26, 2009. Patients were randomized to duloxetine monotherapy (n=138), pregabalin monotherapy (n=134), or a combination of duloxetine and gabapentin (n=135). The primary objective was a noninferiority comparison between duloxetine and pregabalin on improvement in the weekly mean of the diary-based daily pain score (0- to 10-point scale) at end point. Noninferiority would be declared if the mean improvement for duloxetine was no worse than the mean improvement for pregabalin, within statistical variability, by a margin of –0.8 unit. The mean change in the pain rating at end point was –2.6 for duloxetine and –2.1 for pregabalin. The 97.5% lower confidence limit was a –0.05 difference in means, establishing noninferiority. As to adverse effects, nausea, insomnia, hyperhidrosis, and decreased appetite were more frequent with duloxetine than pregabalin; insomnia, more frequent with duloxetine than duloxetine plus gabapentin; peripheral edema, more frequent with pregabalin than with duloxetine; and nausea, hyperhidrosis, decreased appetite, and vomiting, more frequent with duloxetine plus gabapentin than with pregabalin. Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin. Trial Registration: clinicaltrials.gov Identifier: NCT00385671