Comprehensive assessment and pulsed electromagnetic therapy for diabetic peripheral neuropathy

Abstract

Diabetic peripheral neuropathy (DPN) is a major risk factor in developing diabetic foot ulcers. Sensory deficits and hardening of plantar soft tissues are commonly found in people with DPN, which should be monitored carefully since these are risk factors in developing foot ulcers. Semmes-Weinstein monofilament (SWM) is a reliable, widely used measurement tool that examines sensory deficits in the foot in clinical settings. However, there is no consensus on either the size choice of monofilament or the assessment site for DPN screening. The Tissue Ultrasound Palpation System (TUPS) is an instrument that measures the biomechanical properties of plantar soft tissues, which may be a potential tool for detecting DPN. Currently, there is a lack of non-pharmacological intervention for DPN. Pulsed electromagnetic field (PEMF) therapy is known to increase blood circulation that may promote regeneration of peripheral nerves. However, few studies have examined the effects of PEMF stimulation in people with DPN and this area has not been fully explored. Therefore, this thesis consists of three inter-related studies. The first study examines the thickness and stiffness of plantar soft tissues in subjects who suffer from DPN, compared to healthy control subjects. In addition, the relationship between the stiffness and thickness of plantar soft tissues with subject demographic characteristics, foot sensation, sensory nerve functions, and blood glucose level were explored. Secondly, the sensitivity and specificity of the stiffness measurement of plantar soft tissues and SWM for detecting DPN in a group of people with diabetes was studied. Thirdly, a randomized placebo controlled trial was conducted to compare the effects of 10 daily sessions of active PEMF stimulation (Duration: 30 minutes; frequency: 10 Hz; and intensity: 40 Gauss) to placebo PEMF stimulation. The outcome measures used in this study were the plantar sensation, Sural nerve conduction test and biomechanical properties (i.e. thickness and stiffness) of plantar soft tissues in people with DPN. In the first study, the plantar soft tissues thickness and stiffness were measured by TUPS in 69 subjects with DPN and 41 healthy control subjects. Our results showed that there was no significant difference in thickness of plantar soft tissues between the DPN group and the control group over the four sites. However, the plantar soft tissues of DPN group were stiffer than those of the control group over the big toe (p = 0.002), the first metatarsal head (p = 0.033), and the second metatarsal head (p = 0.003). Multiple linear regression analysis was then used to determine which clinical variables were most strongly associated with thickness and stiffness of plantar soft tissues. A relatively small variance (6%) of thickness of plantar soft tissues under the first metatarsal head was explained by the length of DM history in the DPN subjects (p < 0.01). About 35% of the variability of thickness of plantar soft tissues at the second metatarsal head of the DPN group could be explained by age, body weight, and foot sensation (p < 0.001). The HbA1c level and body weight explained 29% of the heel thickness of the DPN group (p < 0.001). Nineteen per cent of the variability in heel stiffness of the DPN group was explained by the heel thickness and the Sural nerve conduction velocity (p < 0.01), while 15% of the variability in the second metatarsal head was explained by Sural nerve conduction velocity and the fasting blood glucose level (p < 0.01). For the control group, the independent variables were able to predict the variability of the stiffness measurement, but not the thickness measurement. Fasting blood glucose explained 13% of the variability in plantar soft tissue stiffness at the big toe. The amplitude of Sural nerve action potential explained 10% of the variability of stiffness in plantar soft tissue at the second metatarsal. Thickness of plantar soft tissue at the heel region and the amplitude of Sural nerve action potential explained 29% of the variability of stiffness in plantar soft tissue at the heel. Sixty-one subjects with diabetes participated in the second study, of whom 18 have confirmed the diagnosis of DPN by reduced Sural nerve conduction velocity and action potential amplitude. All subjects were assessed with TUPS over four plantar regions and three SWM over 10 foot regions. The sensitivity and specificity for DPN screening with stiffness measurement of plantar soft tissues by TUPS and SWM tests were calculated. The mean values of plantar soft tissues stiffness of healthy control subjects obtained in the first study were used as the cut-off points for having abnormally high plantar soft tissues stiffness for the DPN subjects in this exploratory study. The stiffness of plantar soft tissues at the second metatarsal head obtained the best balance between the sensitivity (56%) and the specificity (70%), which was comparable to that of the monofilaments. When using more than 40% of foot regions (4 out of 10 sites) that were insensate to the monofilament was used as the cut-off point, the SWM 4.31 (sensitivity: 78%, specificity: 63%) had a better balance in sensitivity and specificity than the SWM 4.17 (sensitivity: 94%, specificity: 21%) or SWM 5.01 (sensitivity: 39%, specificity: 91%). In the third study, a randomized controlled trial was performed. Forty-seven subjects with DPN were randomly allocated to receive 10 daily sessions of active PEMF treatment or placebo treatment. The assessor and the subjects were not aware of the type of treatment they received. The number of sites in the foot that was insensate to SWM 4.31 was documented. Sural nerve conduction test and the measurement of thickness and stiffness of plantar soft tissues were also conducted. The subjects were assessed in the initial session, in a final session, and in a one-month follow-up. Repeated measures ANCOVA found no significant difference between groups for all outcomes. Age, body weight, body mass index and HbA1c level were used as co-variates in the repeated measures ANCOVA analysis since significantly between-group differences (p < 0.05) were observed in those data. In conclusion, our findings demonstrated that people with DPN have stiffer plantar soft tissues as compared to non-diabetic control subjects. The use of TUPS for measuring stiffness of plantar soft tissues at the second metatarsal head seems to be a good tool for detecting people with DPN. Moreover, the use of SWM 4.31 is probably a better choice for detecting DPN than SWM 4.17 and SWM 5.07, due to a better balance in sensitivity and specificity. Ten daily sessions of active PEMF stimulation (Duration: 30 minutes; frequency: 10 Hz; and intensity: 40 Gauss) produced no significant effects in improving plantar sensation, Sural nerve conduction test, thickness and stiffness of plantar soft tissues for people with DPN when compared with placebo PEMF stimulation. A future study, with a larger sample size, investigating the long term treatment effects of PEMF on the signs and symptoms of DPN patients, is warranted.