Demographic Characteristics of Persons with Diabetes Mellitus and Peripheral Neuropathy Sharada Tata M.S., Stephen Morewitz, Ph.D.

, Kea Hong Tan, Joel Clark, D.P.M.

Abstract Background: Studies have established a positive association between peripheral neuropathy (PN) and diabetes mellitus (DM). The purpose of the present investigation is to determine the predictor variables for demographic characteristics of persons with DM and peripheral neuropathy. Method: Results: Among persons with and without DM, males are more at risk to develop complications related to PN, such as foot insensate areas and numbness in extremeties. Persons with DM over 61 years old are at higher risk than other age groups. Among PN diabetic patients, females are more likely to suffer from emotional disorders like panic, anxiety disorder, and depression than males of the same age or younger. Conclusion: Predictor variables will assist clinician in better diagnosing PN, contributing in more effective treatments and shortening of healing time. Diagnosing measures to be taken into consideration include race, age, education, marital status, duration of DM, numbness in hands or feet, participation of moderate physical activity, and use of tobacco. Introduction: PN is commonly characterized as one of the prevalent lower extremity diseases (LED) among persons with DM. One report showed that approximately 18% of persons aged 40 and above had LED, and that LED was twice as prevalent among persons with DM than among persons without DM (1). DM was one of the major causes of morbidity and mortality in the United States that generated high socio-economic costs (2;3), with many complications, such as myocardial

infarctions, kidney failure, depression, anxiety disorder, PN, and amputations of the body (4,5,6). PN can be observed by abnormal gait, caused by muscle weaknesses, loss of reflexes in the ankle, foot deformities (e.g. hammertoes and collapse of mid foot), blisters and sores in the numb areas of the foot, foot injuries, ulceration, or infection that may lead to amputation (7). Most of the amputations caused by PN and poor circulation can be prevented by taking special care of foot and preventing untreated foot injuries in persons with DM (8). Another report on gender differences in the onset of diabetic neuropathy showed males developed neuropathic complications at age 63, approximately four years in advance of females (9). However, a difference in the progression and manifestation of diabetic neuropathy between men and women may exist. Methodology A population-based sample of 10122 adults - inclusive of individuals with and without DM from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) were analyzed using multivariate statistical procedures. 2003-2004 NHANES allowed for large sub-samples to test our hypothesis and also provided the opportunity to compare our results with other similar studies. Statistical analysis study was conducted on variables number of insensate areas in left and right foot from Lower Extremity Disease Peripheral Neuropathy Examination data. PN participants in the data collected were over 40 years old (NHIS, 2006). SAS and SUDAAN statistical tools were used for the analysis of these data. A master database was used for this study, which is a collection of different data sets. This database enabled a substantial sample to conduct various statistical procedures. Correlational analysis was conducted between number of insensate areas in left and right foot and numbness in hands/feet in the last 3 months that were split by sex, different age groups, and in

persons suffering from DM. The possible associations between number of insensate areas in right and left foot among different gender, origin, race, education, marital status, and duration of DM were analyzed with general linear model. To test the significance of the relationship between categorical variables to the number of insensate areas, Chi-square statistic was performed. CochranMantelHaenszel (CMH) chi-square statistics were performed to test for homogeneity of population. Result: The results from this sample are gender biased. The total number of males (N=4970) is lower than females (N=5152) (Table 1). However, both gender showed positive association (parameter) to number of insensate areas in both feet with numbness in hands/feet in the last three months irrespective of whether they had DM. Age group was categorized as < 25 years old, 26-40 years old, 41-60 years old, and > 60 years old. Males and females of age 61 years and above showed the highest significant association (r= +0.23, p=.0001, = 0.05), indicating that having insensate areas in both feet is significantly associated with having numbness in hands/feet. In contrast, there was no significant association among persons with DM of younger age groups. Various measures of the population were collected as a part of survey, such as Education people who completed less than high school, high school or more than high school, Marital Status divorced, married or other (Other- consisting of people who are married less than a year, living with partners or separated), Duration of DM- this variable consists a representative sample of people suffering from DM for a year or less than a year. Other variables include gender, race, and origin and are self explanatory (See Table 1 for more details).

Frequency analysis was conducted on variables Foot Pain- right foot/ left foot, race, education, origin (Mexican American/Other Hispanic), marital status, duration of DM, age (further divided into age groups), moderate physical activity after dividing them by gender. Chi-square statistic was calculated as a part of the frequency analysis and is significant for all variables except left foot and origin and duration of DM. This indicates that pain in left foot and duration of DM are not dependent on gender. The non significance also indicates that no direct conclusions can be derived from persons with DM suffering from left foot pain and in patients suffering from DM for a year with regard to gender. The variables Left foot with pain, Right Foot with pain and Numbness in hands/feet in the past three months were also fit in general linear model analysis to better explain the variations in outcomes. All the three variables are significant (Table 2). These results indicate that gender is one of the most important variables that should be considered while providing treatment for individuals with DM. Chi-square statistic was not significant for left foot. Therefore, we subjected the variable, Numbness in Hands/Foot in the past three months, to logistic procedure. Both right foot and left foot were significant. These results indicate that tingling/numbness in both feet/ hands is a major symptom in treating PN. We further conducted analysis of variance (ANOVA) on the three variables number of insensate areas in left and right foot and numbness in significant hands/feet in past 3 months to demonstrate the effect of other predictor variables and their interactions on these variables. Number of insensate areas was quantified with 0, 1, 2, 3, and -1. 0 denotes all sensate or no insensate areas while 1, 2, and 3 corresponds to the numbers of insensate areas on each foot. -1 represents data that could not be obtained or missing. -1 data have been renamed as Other and were not included as they were insufficient to represent information in the study.

The data were subjected to ANOVA analysis to further study the interaction of predictor variables--sex, age-group, duration of DM, marital status, and education on left and right foot pain. These interactions play a vital role in suggesting treatments to PN patients. Significant interactions of variables for number of insensate areas in left foot were: (1) gender and duration of DM; (2) gender, age group, and duration of DM; (3) sex and education; (4) age group and education; (5) duration of DM and education; (6) sex, duration of DM, and education; (7) age group, education, and duration of DM. Significant interactions for number of insensate areas in right foot were: (1) age group and education; (2) age group, education, and duration of DM; (3) sex, age group, education, and duration of DM; (4) marital status and duration of DM. The variable, education, is significant for numbness in hands/ feet in the past three months. When the analysis states that an interaction is significant, it means that the variable should be given consideration while suggesting treatment to neuropathic patients. Therefore, from the above analysis, when it states that interaction of variables age group and education and age group, education, and duration of DM are significant for both left and right foot pain it means that the variables, age group, education, and duration of DM of the patient should be considered while suggesting treatment. Patients from younger age group and older age group differ in treatment; patients with education and without education differ in understanding the gravity of the severity of symptoms. Also, duration of DM plays an important role in suggesting treatment for PN patients. The statistical analysis of the study indicated that compared with males with DM, the females were, on average, older, Mexican American, divorced, and have higher education level. Moderate activity was observed more frequently in males with DM than in females, showing an inverse relationship with number of foot insensate areas. Because the sample size is large, the standard error mean values are small for all variables.

The general linear model for the variables yielded significant interactions for the predictor variables, sex, duration of DM, and have DM, are significant with a p-value = <0.001 for right and left foot (See Appendix Table 2). The interactions of the variables were found not significant. To explain the outcome of variable, sex, over number of insensate areas in left and right foot further, we fit the variable, sex, in logistic regression model. The chi-square statistic was calculated and found significant with a p-value = <0.001 for both males and females. Conclusion Males with DM have higher risks of developing PN. Other predictor variables include race, age, education, marital status, duration of DM, numbness in hands or feet, and moderate activity. Males with DM are also more prone to suffer from more foot insensate areas than female with DM. The frequency of females suffering from DM over one year is higher than for males. Persons with DM who have the habit of exercising are at lower risk for PN than those who do not exercise. Persons with DM over the age of 61 have higher risk of developing PN than all younger age groups. Gender and age differences should be taken into consideration for persons with DM and PN to ensure earlier detection and better treatment outcome. Male with DM can be less communicative about their pain levels or some of them may simply have higher tolerance for pain. Numbness in hands/feet should not be dismissed merely as signs of aging but utilized for early detection of PN. Another consideration to bear in mind is the use of tobacco, since cigarette smoking is known as a risk factor not only for PN but also other peripheral vascular diseases (7). Clinicians should include routine examination for symptoms including pain, tingling sensation, numbness, and loss of feeling in the upper and lower extremities. Standard foot exam, which was covered in a 2004 American Diabetes Association include five simple clinical tests, namely the 10-

g monofilaments, 128-Hz tuning forks, Pinprick sensation, Achilles tendon test, and vibration perception threshold testing (10). Alternative treatments like acupuncture and massage also might be suggested to alleviate pain in elderly patients. Physical therapy may also help improve weakness in muscle or loss in coordination of limbs (8). As for neuropathic ulceration management, foot off-loading has shown to be effective in reducing plantar pressure and shortening healing time (11). Of all off-loading methods, total-contact cast was found to be the most effective for both infected and uninfected neuropathic ulcers (12).

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http://diabetes.niddk.nih.gov/dm/pubs/neuropathies. Accessed March 5, 2011. 11. Bus SA, Valk GD, van Deursen RW, et al.: The effectiveness of footwear and offloading interventions to prevent and heal foot ulcers and reduce plantar pressure in diabetes: a systematic review. Diabetes Metab Res Rev, 24(1): 162180, 2008. 12. Armstrong AG, Nguyen HC, Lavery LA: Off-loading the diabetic foot wound. Diabetic Care, 24(6): 1019-22, 2001. Appendix