Being overweight is associated with decreased peripheral nervous system (PNS) function. Recent studies strongly suggest that obesity and its complications play a significant role in the development of peripheral neuropathy. An inverse relationship between body mass index (BMI) and nerve conduction measures has been demonstrated (6). Overweight individuals also have significantly lower motor and sensory nerve action potential (SNAP) amplitudes compared with normal weight subjects (17). Higher waist circumference and BMI are independently associated with polyneuropathy (24,27). Furthermore, many clinical associations of obesity are related to PNS function complications (16,24,28).
Being overweight or obese is inversely related to physical activity and maximal oxygen uptake (V˙O2max) (20,21). Among patients with type II diabetes, physical activity has been suggested to reduce the risk of neuropathy (1). Previous studies have shown that hypertrophic changes occur in motor neurons owing to periods of increased use (7,25), which may lead to faster motor nerve conduction velocities (13). These findings suggest that physical activity may also have direct effects on the PNS function. Conversely, evidence suggests that PNS function directly affects physical performance. A recent study indicated that poor peripheral nerve function has a direct, detrimental effect on physical performance rather than an indirect effect through decreasing muscle function (23).
Although overweight and obese people tend to be physically inactive and unfit, little is known about the association among V˙O2max, physical activity, and PNS function among overweight individuals. In this study, we evaluated the relationship among V˙O2max, physical activity, and PNS function with the hypothesis that, in overweight individuals, V˙O2max and physical activity are positively associated with PNS function.
Forty overweight adults (age 28-68 yr) were recruited from an outpatient obesity clinic. The inclusion criterion was a BMI of ≥25 kg·m−2 without type II diabetes or excessive use of alcohol. Five individuals were taking asthma medication, three were on blood pressure medication, two were on cholesterol medication, two were on thyroxin medication, and one was taking hormone replacements. Height was measured without shoes to the nearest 0.5 cm. Weight was measured on a calibrated scale to the nearest 0.1 kg. All individuals gave their informed consent, and the study was approved by the local ethical committee.
Self-rated physical activity was determined by a modified Paffenbarger questionnaire, where individuals were asked to recall their physical activity at the ages of 15 yr, 30 yr, and their current age. Individuals were classified by the highest level of exercise they performed for at least 15 min per session at least three times per week. Categories were strenuous (e.g., jogging), moderate (e.g., walking), mild (e.g., fishing), and less than mild (e.g., watching television). Physical activity indexes (PAI) were then scored, giving 1 point to less than mild exercise, 2 points to mild exercise, 3 points to moderate exercise, and 4 points to strenuous exercise (11,14). The amount of daily physical activity was measured by a wrist-held accelerometer (AW 200; Polar Electro Oy, Kempele, Finland), which also has a pedometer function (5). Individuals were asked to wear the accelerometer for a 24-h period. The sum and median of the intensity of the acceleration pulses, as well as the number of steps, were determined.
Fasting and 120-min glucose levels were measured by a standardized 75-g oral glucose tolerance test to confirm the absence of type II diabetes. Serum glucose levels were determined using a hexokinase assay (Konelab analyzers; Thermo Electron Oy, Vantaa, Finland).
All individuals underwent an incremental bicycle ergometer test (ERG 911; Schiller AG, Bitz, Germany) with V˙O2max analysis (Oxygen Pro spirometer; Jaeger, Viasys Healthcare, Inc., Hoechberg, Germany). The initial workload was 25 W, which was increased by 25 W every 2 min until the individual was exhausted.
Peroneal motor nerve and radial, sural, and medial plantar sensory nerve conductions, with standard distance, were measured bilaterally using Keypoint 4 and Keypoint portable devices (Medtronic, Skövlunde, Denmark). Using surface electrodes, sensory nerve conductions were measured antidromically for the radial and sural nerves and orthodromically for the medial plantar nerves. For motor nerve conduction measurements, the distal and proximal latencies, distal and proximal peak-to-peak compound muscle action potential (CMAP) amplitudes, nerve conduction velocity (NCV), F-wave minimum, mean and maximum latencies, F-wave dispersion, and F-wave amount per 20 stimuli (persistence) were determined. For sensory nerve conduction measurements, the onset latency, peak-to-peak SNAP amplitude, and NCV were determined. Skin surface temperature was measured immediately after the conduction measurements. Filter settings were 2 Hz to 10 kHz for motor nerve conduction measurements and 20 Hz to 2 kHz for sensory nerve conduction measurements.
Mean ± SD values were used as descriptive statistics. The univariate association between explanatory and response variables was analyzed using a Pearson correlation coefficient. All variables significant in univariate analyses were entered into the multivariate analyses. Multiple stepwise linear regression analysis was used to assess the relationship among V˙O2max, PAI at the age of 30 yr, number of steps, and nerve conduction measurements. Closely interrelated variables were entered separately in these models. All models were adjusted for age, height, and skin temperature, all of which have been shown to be associated with nerve conduction measures in previous studies. The Benjamini-Hochberg procedure was used to correct P values for multiple comparisons (4). A corrected P value of <0.05 was considered statistically significant. In all tests, P < 0.05 was considered statistically significant. The statistical program used was SAS 9.1 (SAS Institute, Inc., Cary, NC).
Table 1 shows the characteristics of the 40 study participants. The mean ± SD age of the individuals was 49 ± 11 yr, and 26 (65%) of the participants were women. Two individuals had impaired fasting glucose (fasting glucose ≥ 6.1 mmol·L−1), and two individuals had impaired glucose tolerance (fasting glucose ≥ 6.1 mmol·L−1 and 120-min glucose ≥ 7.8 mmol·L−1). The mean BMI was 34 kg·m−2 (range = 25.9-49.5 kg·m−2) in women and 33 kg·m−2 (range = 27.0-42.4 kg·m−2) in men. The mean ± SD V˙O2max was 22.6 ± SD 4.7 mL·min−1·kg−1 for women and 31.8 ± SD 6.3 mL·min−1·kg−1 for men. The mean ± SD values of peripheral nerve conduction measures are shown in Table 2.
V˙O2max correlated positively with peroneus distal CMAP amplitude (r = 0.49, P = 0.002; Fig. 1), peroneus proximal CMAP amplitude (r = 0.45, P = 0.004), and F-wave persistence (r = 0.50, P = 0.001). PAI at the age of 30 yr was significantly correlated with F-wave dispersion (r = −0.34, P = 0.03), medial plantar sensory latency (r = −0.43, P = 0.007), and medial plantar sensory NCV (r = 0.33, P = 0.04). The association between the number of steps measured by an accelerometer and sural SNAP amplitude was of borderline significance (r = 0.31, P = 0.06). BMI correlated negatively with V˙O2max (r = −0.48, P = 0.001), sum of acceleration pulses' intensity (r = −0.41, P = 0.01), and number of steps (r = −0.35, P = 0.03). The sum and median of the intensity of the activity pulses and other physical activity age indexes were not associated with nerve conduction measures.
In multiple stepwise regression analysis, after adjusting for age, height, and skin temperature, BMI was a significant predictor for medial plantar SNAP amplitude variation, with coefficient of determination of 23% (Table 3). After adding V˙O2max to the regression models, BMI no longer explained the medial plantar SNAP amplitude variation. The results of the final multivariate regression analyses are shown in Table 4. V˙O2max explained 17% of the peroneal distal CMAP amplitude variation and 16% of the peroneal proximal CMAP amplitude variation. In addition, V˙O2max was a significant predictor of F-wave persistence, radial sensory NCV, and medial plantar SNAP amplitude variation, with coefficients of determination of 18% (0.35 increase per unit), 12% (0.18-m·s−1 decrease per unit), and 22% (0.47-μV increase per unit), respectively.
There was a significant positive association between PAI at the age of 30 yr and nerve conduction measures. PAI at the age of 30 yr was significantly associated with peroneal motor NCV, peroneal F-wave maximum latency, medial plantar sensory latency, and NCV variation, with coefficients of determination of 9% (0.98-m·s−1 increase per unit), 8% (1.23-s decrease per unit), 14% (0.10-s decrease per unit), and 10% (1.47-m·s−1 increase per unit), respectively (Table 4).
A positive association between the number of steps measured by the accelerometer and medial plantar SNAP amplitude variation was found, with a coefficient of determination of 10% (0.0005-μV increase per unit), respectively (Table 4).
In this study, we showed for the first time an association between physical activity and fitness and PNS function in overweight individuals. Our results suggest that V˙O2max and physical activity are positively associated with PNS function, providing new evidence for the health-related benefits of physical activity in overweight individuals.
Being overweight or obese is associated with various disorders such as hypertension, hyperlipidemia, insulin resistance, impaired glucose tolerance, and type II diabetes. The increased risk of polyneuropathy in type II diabetes has been well recognized, and recent studies have also shown that incipient type II diabetes increases the risk of polyneuropathy (12,19,22,28). Mounting evidence suggests that BMI greater than 25 kg·m−2 is an important risk factor for developing polyneuropathy.
Cardiorespiratory fitness is associated with improved health and decreased morbidity and is inversely related to chronic diseases such as cardiovascular disease (3), high blood pressure (21), metabolic syndrome (15), impaired glucose tolerance, and type II diabetes (26). We hypothesized that cardiorespiratory fitness and physical activity are associated with PNS function even in overweight or obese individuals known to be at increased risk of developing polyneuropathy. In our study, V˙O2max was significantly associated with peroneal CMAP amplitudes and F-wave persistence, supporting our hypothesis.
Previous studies have suggested that V˙O2max, assessed with maximal exercise testing, is a better measure of health outcomes than physical activity alone because fitness assessment is less prone to misclassification (2). V˙O2max reflects cardiorespiratory fitness and does not reveal the type of physical activity done by an individual. Furthermore, V˙O2max does not leave space to identify either how much or what form of physical activity would be optimal when considering PNS function. Therefore, we also measured self-rated PAI and used accelerometers to evaluate individuals' physical activity. PAI at the age of 30 yr was significantly associated with both motor and sensory nerve conduction measures, further supporting our hypothesis that physical activity is positively associated with PNS function. The number of steps measured by an accelerometer in a 24-h period was positively associated medial plantar SNAP amplitude. Our results are in accordance with previous studies, demonstrating the favorable effects of physical activity on PNS function.
Several mechanisms are described in the literature, which might explain our findings. According to a recent study, voluntary exercise increased axonal regeneration through a neurotrophin-dependent mechanism (18). Another study observed that the concentration of Na+/K+-ATPase increased because of exercise (10). In both large and small vessels, exercise augments endothelial NO-dependent vasodilatation (9). Evidence suggests that hypertrophic changes occur in motor neurons owing to periods of increased use (7,25), helping explain the faster motor nerve conduction velocities in athletes compared with those in nonathletes (13). Furthermore, Fisher et al. (8) demonstrated several physiological improvements after moderate exercise in individuals with diabetic neuropathy, including an increase in cardiorespiratory fitness, motor conduction velocities and CMAP amplitudes, sensory conduction velocities and SNAP amplitudes, and F-wave latencies.
This study has some limitations. Our ability to draw definitive conclusions was limited by this study's relatively small sample size. Owing to the cross-sectional design, we cannot provide evidence of causality, and thus, our study does not explore the role of physical activity in the prevention or treatment of polyneuropathy. A 24-h measurement period with an accelerometer represents only a sample of an individual's average activity. Subjective physical activity can be prone to misclassification, which should be taken into consideration. No assessment of peripheral arterial disease was made. Increased subcutaneous tissue owing to overweight may have affected the accuracy of our neurophysiological data. Finally, our study population was middle-aged, which limits the generalizability of these findings to older populations.
We conclude that aerobic fitness and physical activity are positively associated with PNS function in overweight adults. Our results provide further evidence on the need to promote physical activity in the health counseling of overweight people. To evaluate the quantity and quality of the exercise and to identify the importance of exercise as a preventive method of polyneuropathy, dose-response intervention studies in overweight people are needed.
This study was funded by the Ministry of Education, Finland, and was partly supported by the Academy of Finland.
The authors thank Professor Uolevi Tolonen and Hannu Kaikkonen for their contributions to the experimental data. The authors also thank Polar Electro Oy, especially Mr. Hannu Kinnunen, for providing the accelerometers used in this study.
The results of the study do not constitute endorsement of any product by the authors or by the American College of Sports Medicine.
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