Functional status mediates the association between peripheral neuropathy and health-related quality of life in diabetics

Patients with diabetic peripheral neuropathy (DPN) have worse health-related quality of life (HRQoL) compared to patients without DPN, partly mediated by functional status parameters. Effective interventions targeting functional status may be beneficial in improving HRQoL in these patients. 

Diabetic patients are known to have the low quality of life (QoL). Diabetic peripheral neuropathy (DPN) accounts to be a most common complication in diabetes patients affecting almost 50% of the diabetics. Distal symmetric sensorimotor polyneuropathy is the most common type of peripheral neuropathy which causes sensory loss in a glove and stocking pattern. Patients with DPN are more prone foot infections and ulcerations which may, in turn, lead to an amputation and may be death.

Patients with DPN are known to have the more reduced health-related quality of life (HRQoL). Previous studies have reported that DPN patients tend to suffer from reduced proprioceptive senses, ankle mobility, range of motion and muscle strength. Individuals with DPN also results in reduced balance gait and mobility alterations and increased risk of falls. However, it is unclear, that these functional deficits in individuals with DPN are associated with, and responsible for, reduction in HRQoL.

Therefore, the present study determined the reduction in HRQoL associated with DPN, identify functional deficits among patients with DPN. They hypothesized that patients with DPN have functional deficits compared with non-DPN diabetic patients, and these deficits account for the reduction of HRQoL.

Rationale behind the research:

None of the study evaluated the association of functional deficits in individuals with DPN with reduction in HRQoL.

Therefore, Riandini T et. al. conducted this study to quantify the reduction in HRQoL associated with DPN, identify functional deficits among patients with DPN in terms of muscle strength, range of motion, balance functional tasks, and balance confidence, and examine the role of these functional deficits in the reduction of HRQoL.

Objective:

To quantify the reduction in HRQoL associated with DPN, identify functional deficits among patients with DPN in terms of muscle strength, range of motion, balance functional tasks, and balance confidence, and examine the role of these functional deficits in the reduction of HRQoL.

Study outcome measures:

• HRQoL

EQ-5D-5L: The EQ-5D-5L is a generic measure of HRQoL, comprising a health descriptive component and a visual analogue scale (VAS). The health descriptive component consists of five dimensions, one each on mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each item has five levels of response: no problem, slight problem, moderate problem, severe problem, and extreme problem. EQ-5D scores can be summarized into a single index value, the health utility score, using population preference weights. This index ranges between 0 and 1, where 1 represents perfect health and 0 represents death.

• Physical function assessment: Muscle strength at ankle and big toe were measured by using a handheld dynamometer positioned on the dorsum of the foot and proximal phalanx of the great toe, respectively, with the patient seated, and knees extended. Range of motion at ankle was measured by using a handheld inclinometer placed on the dorsum of the foot, with the patient seated and knees extended and starting with the ankle fully plantar flexed. Range of motion at knee was measured for flexion–extension at the joint using the handheld inclinometer placed on the lower third of the back of the leg of interest, with the participant standing with the knee extended at the start. After a mock run, two trials were conducted for each measure and the mean was taken.
• Participants were assessed on their functional capability using the timed up and go (TUG), five times sit-to-stand (FTSTS) and functional reach tests. The TUG is a test of mobility and measures the time taken by a participant to rise from a seated position, walk three meters forward, walk back and be seated. The FTSTS is a test of functional strength and measures the time taken for a participant to rise from and return to a seated position five times in a row. The functional reach test is a measure of balance during tasks and measures the distance a person can reach forward with his arm while standing without losing balance. A practice test was administered before the actual test for each measure.
• A balance platform (Accugait, AMTI, USA) was used to measure average body sway velocity with the participant standing with eyes closed for 2 min. Two runs were conducted for each participant and the mean was taken.
• Balance confidence was measured using the Activities-specific Balance Confidence (ABC) scale, a 16-item instrument that assesses individuals’ confidence in performing daily or routine activities without losing their balance. Each item is rated from 0 to 100% in terms of level of confidence, and the total score is the average of all individual item scores.

Time period: Write the time period at which outcomes were studied like baseline, 2 weeks and 6 weeks. 

Study Outcomes

• Functional status and HRQoL:

Participants with DPN had lower ankle dorsiflexion strength (right −0.74 lbs, 95% CI −1.54, 0.06 lbs, p=0.068; left −0.92 lbs, 95% CI −1.71, −0.13 lbs, p=0.023) and great toe extensor strength (right −1.2 lbs, 95% CI −1.92, −0.48 lbs, p=0.001; left −1.08 lbs, 95% CI −1.75, −0.41 lbs, p=0.002), poorer performance on TUG test (2.07s, 95% CI 0.92, 3.22s, p<0.001) and FTSTS test (1.87s, 95% CI 0.12, 3.61s, p=0.036), as well as greater body sway velocity while standing with eyes closed (0.50mm/s, 95% CI 0.19, 0.81mm/s, p=0.002). They also had significantly lower health utility score (−0.10 points, 95% CI −0.15, −0.06s, p<0.001) compared to participants without DPN. HRQoL differed in DPN and non-DPN groups in all dimensions except pain/discomfort.

• In the multivariable analysis, only DPN status, FTSTS, body sway velocity, BMI, gender, diabetes duration, and burning pain were significant predictors of health utility score with explanation of 37.80% of total variance in HRQoL in Model 1. Addition of ABC score in Model 2 resulted in explanation of 45.35% of total variance in HRQoL. In this model, FTSTS turned out to be non-significant (p=0.254), probably due to stronger correlation between ABC score and health utility score as well as strong correlation between ABC score and FTSTS of −0.544 (p<0.001). Correlations between ABC score and functional measures ranged from 0.0456<|r|<0.5440. Age of participants, although significantly different between DPN and non-DPN groups, was not significantly associated with HRQoL. Employment status was significantly associated with HRQoL on bivariate analysis but did not appear as a significant predictor in both models. Diabetes duration significantly differed between the two groups and was associated with HRQoL with borderline significance, after adjusting for functional status and other confounding factors. Burning pain was no longer significant in Model 2.

• Structural equation modelling of the final model showed direct association of that DPN status with HRQoL, as well as indirect associations through functional status. There were significant individual paths from DPN status to FTSTS (β=−1.9, SE=−0.17, p=0.033), from FTSTS to ABC score (β=−1.8, SE=−0.52, p<0.001), and from ABC score to HRQoL (β=0.0041, SE=0.52, p<0.001), suggesting that FTSTS and ABC score mediated the relationship between DPN and HRQoL (Figure 1). All other paths were significant and consistent in terms of the magnitude and direction of associations with the multiple linear regression model, except for the paths from body sway velocity to HRQoL which did not reach significance (β=−0.014, SE=−0.091, p=0.17). The overall model showed reasonably good ft with χ2 =8.075 (p=0.044), RMSEA=0.103 (lower bound 0.015, upper bound 0.191), CFI=0.966, TLI=0.887, and SRMR=0.053. 

Figure 1: SEM analysis of HRQoL predictors

This study demonstrated that patients with DPN had a significantly lower HRQoL and lowered functional status compared to those having diabetes without DPN. Mean utility score in the non-DPN group in this study was similar to that reported in Europe among people with diabetes patients without complications (mean=0.74, SD=0.27). The utility scores in the DPN group in this study, however, were comparable to the scores reported in patients with other conditions from this region, such as breast cancer (mean=0.78, SD=0.16), age-related macular degeneration (mean=0.89, SD=0.14), and end-stage renal disease (mean=0.60, SD=0.21). It is evident that the impact of DPN on HRQoL could be similar or even worse than other severe conditions.

In the present study, domains of mobility, self-care, usual activity as well as anxiety were associated with DPN, while the pain was not. It was shown that DPN is associated with significant reduction in HRQoL, with greatest declines seen in the physical function/ mobility and pain domains. The recent findings are also consistent with previous work in this area. From this study, it is well recognized that DPN leads to specific sensorimotor deficits, with consequent limitations in balance or postural stability, functional strength, gait, and mobility. However, few previous studies have empirically demonstrated the link between either specific neurological deficits or functional measures with HRQoL in individuals with DPN. To our knowledge, only one previous pilot study has reported on this relationship, finding significant associations between HRQoL (assessed by EQ-5D-3L) and functional mobility in older patients with diabetes. While the role of functional status in HRQoL has been previously demonstrated in patient populations with known functional disability, like the elderly and those with multiple sclerosis.  In this study, the authors investigate the role of functional status in patients with DPN on HRQoL and examine the inter-relationships between DPN, functional status, and HRQoL.

The actual relationships among these variables could be complicated and reciprocal. For example, it is possible that lower HRQoL in patients with diabetes may alter their self-care and diabetes management behaviors, which in turn could put them at higher risk of developing complications and further decrease HRQoL. In our analysis, balance confidence was significantly correlated with functional status measures and dominated the relationship with HRQoL as the most reliable predictor. Based on our results, the mediating paths from FTSTS to ABC score and from ABC score to HRQoL were both significant. This might explain why FTSTS became non-significant when ABC score was included and suggests mediation between FTSTS and HRQoL by balance confidence. ABC score, however, did not mediate the relationship between body sway velocity and HRQoL; therefore, balance confidence appears to be a mediator of certain functional measures only. In many studies, HRQoL was also associated with socioeconomic factors. Similar associations have been reported previously in patients with diabetes and underline the need for tailored clinical-social interventions in specific subgroups to improve health outcomes. However, since most studies have been cross-sectional, it is also unclear whether employment and income levels are the cause or effect of DPN and HRQoL status. 

The patients with DPN tend to have significantly lower HRQoL. Results indicate that increased functional status and balance confidence may prove  to be useful in improving HRQoL in individuals with DPN.