Biochemical parameters and its association with quality of life in patients with diabetic foot ulcers

 

 

Abstract               Background: Diabetic foot ulcer (DFU) is a serious complication of Diabetes mellitus (DM) with significant impact on the quality of life(QoL). Various biochemical parameters can play important role in evaluating QoL in DFU patients. Objective: To evaluate the health related quality of life (HRQOL) in DFU patients and its association with different biochemical parameters in a tertiary care teaching hospital. Methodology: A total of 70 DFU patients from surgery department were enrolled and their demographic and disease related parameters were recorded. They were subjected to undergo routine investigations like CBC, Hb, FBS, PP2BS, HbA1c, lipid profile and serum creatinine levels. HRQOL was evaluated using Cardiff Wound Impact Questionnaire. Association of biochemical parameters as predictors of HRQOL was statistically evaluated. Results: All patients of DFU showed deteriorated HRQOL with mean score of 42.2±15.13 in social domain, 17.12±7.43 in wellbeing, 75.33±27.06 in physical domain and total score of 146.56±45.46.FBS levels were significantly affecting all the domains like social (p=0.03), wellbeing (p=0.049), physical (p=0.04), overall quality of the life (p=0.004) and total HRQOL scores (p=0.009). HBA1c also found to be affecting all the domains including social, wellbeing, physical symptoms score, overall quality and total score(p<0.05). Decrease Hb levels significantly affected social domain (p=0.023), physical symptoms(p=0.014) and total score(p=0.059). BMI was significantly affecting social, physical symptoms, total scores and overall quality life (P<0.01). PP2BS, cholesterol and creatinine levels were not significantly associated with the QOL scores(p>0.05). Conclusion: Biochemical parameters of glycaemic control like FBS, HbA1c can serve as effective predictors of HRQOL in DFU patients. Hb levels and BMI also affects HRQOL. These biochemical parameters can be used for designing the treatment and monitoring regimen for better QOL of patients with DFUs.

Key Word: Diabetes foot ulcer, quality of life, Cardiff Wound Impact Questionnaire, FBS, PP2BS, HbA1c

 

 

INTRODUCTION

Diabetes mellitus (DM) is one of the chronic metabolic diseases. The prevalence of diabetes is increasing worldwide and also in India. It is predicted that by 2030 diabetes mellitus may afflict up to 79.4 million individuals in India.¹ One of the most common diabetic-related complications is the diabetic foot problem. This complication, caused by peripheral arterial disease or peripheral neuropathy, brings about poor ulcer healing, infection, or even leg amputation. Diabetic foot ulcer (DFU) has been identified as common and serious complications of DM which involve about 15% of patients with DM during their lives with significant impact on the quality of life (QoL)² The mortality rate of these patients is 2.4 times greater than those without foot ulcers^3,4. WHO defines Quality of Life as individuals’ perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. It is a broad ranging concept affected in a complex way by the person's physical health, psychological state, level of independence, social relationships, personal beliefs and their relationship to salient features of their environment.^[5] Mainly, limited mobility and increased dependence affects the QoL by impinging upon four aspects- social, psychological, physical and financial. People commonly suffer perceptions of diminished self-worth due to an inability to perform social and family roles⁶. Various researchers have tried to indenify different factors influencing quality of life in diabetes. It had been reported that factors like duration of diabetes, treatment given for it, adherence to treatment, strict glycaemic control achieved are significantly associated with the quality of life in diabetes patients⁷ but only few studies have targeted the population the diabetes foot ulcers. Additionally, patients with DFUs report more depression, less satisfaction with life and poorer psychosocial adjustment to illness than diabetics who do not suffer from foot ulcers⁸. The assessment of HRQOL is of importance in establishing evidence-based treatment protocols. As Gordon et al. states, two patients with the same clinical manifestations often have drastically different perceptions of HRQOL⁹. Reliably measuring HRQOL is of great importance to patients and clinicians because poor HRQOL has been associated with poor ulcer prognosis⁸. Major metabolic problem in the diabetes is lack of insulin in body. Lack of Insulin leads to various metabolic complications in the human body with increases blood glucose, cholesterol, creatinine and transaminases enzyme level and decreases protein content¹⁰. Achievement of tight glycaemic control has been a mainstay of therapy for diabetes. Drug therapy and other non-pharmacological measures are designed in a way to control glucose levels. Periodic monitoring of RBS, FBS, PP2BS, HbA1c etc has been a routine practice in monitoring the progress of diseases as well as outcome of the therapy¹⁰. Considering all these facts, the present study has been planned to evaluate the quality of life in diabetes foot ulcer patients and its association with different biochemical parameters in a tertiary care teaching hospital.

METHODOLOGY

This was a prospective, observational, single center study carried out in the general surgery department of Civil Hospital, Gandhinagar, a tertiary care teaching hospital in western India. The study protocol was presented and approved by an Institutional Ethics Committee (IEC). Patients were explained clearly about the nature and purpose of the study in the language they understood. Written informed consent wasobtained before enrolling the patient for the study. Permission from Medical Superintendent and the Head of the Surgery department was obtained before conducting the study.

Study population: All the patients with age 18 years and above and receiving either preventive care or treatment for an active diabetic foot ulcer or protection of a healed ulcer and able to comprehend and complete the questionnaire attending to the surgery department during study duration (April – June 2018) were included in the study. Patients who were at no current risk of experiencing diabetic foot ulceration, patients unable to attend the clinic during the study period and those having severe cognitive impairment and who refused to consent for the QOL interview were excluded from the study.

Sample size: Taking into consideration “DFU involves about 15% of patients with DM during their lives²”, sample size was calculated by using the formula: 4pq/L² (assuming 10% error and rounding off the value obtained) and sample size of 60 patients were required and considering the dropout rate (10%) from the questionnaire filling, 70 patients were enrolled for the study.

Study procedure details: A total of 70 patients meeting inclusion and exclusion criteria and attended the surgery department enrolled for the study. Patients were approached after they finished consultation with the physician in the hospital. All necessary information like demographic data, history of illness, clinical data and drug treatment were collected by reviewing the hospital case file and by interview with patients. All the information gathered was recorded in the structured case record form. Weight of all patients was measured using a standard calibrated scale placed on the floor. Patients were weighed while standing barefoot and were instructed not to hold onto any form of support. Height was measured with a tape measure and recorded to the nearest centimetre. The patient was requested to stand barefoot with his/her heels together and touching the wall, with his/her back against a wall. Body mass index (BMI) was calculated using Quetelet’s formula (weight (kg)/ height(meter)² and defined using the World Health Organization (WHO) classification (underweight <20 kg/m², normal 20 - 24.9 kg/m², overweight 25 - 29.9 kg/m², and obese >30 kg/m²). All the patients were advised for laboratory investigations on the day of the visit and thereafter patients were interviewed about QOL questionnaire.

Laboratory evaluations: Consent was taken from every subject and they were requested to fast overnight (10 to 12 hours). Blood samples were collected from all subjects in plain and EDTA vacutainer for biochemistry parameters and complete blood count. The serum samples were separated after allowing them to clot by centrifugation at 2500 rpm for 10 minutes at room temperature and analysed for FBS, Lipid profile and serum creatinine on Vitros 250 dry chemistry analyser. And blood samples also collected two hours after meal for PPBS estimation. Blood sugar levels (FBS, PPBS) estimated by glucose oxidase and peroxidase (GOD-POD) method¹¹. Total cholesterol measured by CHOD-PAP method ¹². Serum Triglyceride measured by GPO-PAP method¹³. HDL cholesterol measured by direct enzymatic method ¹⁴.Serum creatinine estimated by modified Jaffe’s enzymatic method¹⁵. HbA1C was measured by Latex enhanced Immunoturbidimetry method on Mispa i2 analyser¹⁶. Complete blood counts including hemoglobin (Hb) were estimated by Diatron abacus 380analyzer.

Questionnaire to measure health related quality of life: Data were collected using case record form which includes information about patients’ demographic characteristics and the factors related to their illness and a separate questionnaire for evaluating the QOL. QOL was assessed using a standardised questionnaire “Cardiff Wound Impact Questionnaire”. The “Cardiff Wound Impact (Quality of Life) Questionnaire” was developed to assess HRQOL in people with chronic wounds of the lower limbs⁸. Pose questions to the person to elicit responses to the 47 screening questions, found in the four domains: ‘Social Life’(14 questions graded on a five point Likert scale), ‘Well-Being’ (7 questions, graded on a five point Likert scale), ‘Physical Symptoms and Daily Living’ (24 questions, graded on a five point Likert scale), and ‘Overall Quality of Life’ (2 questions, graded on a 10 point Likert scale). NOTE: the five point Likert scales use the following response terminology ‘Not at all/not applicable’, ‘Slightly’, ‘Moderately’, ‘Quite a Bit’, and ‘Very’⁸. Total screening score being 245 points. Therefore, with the help of these two questionnaire score of the patient through their response would be counted. The score were analysed in a statistical manner. This instrument was translated in vernacular (Gujarati) language and back translated to ensure content validity. Questionnaire was designed for self-administration but structured interview was conducted to ensure reliability of data. To test feasibility of the instruments pilot study was carried out on 20 patients. It took approximately about 10 minutes to collect data from one patient (consent, history, QOL scale).

Statistical analysis: Microsoft Excel 2007 and open-Epinfo software were used to analyze the data. Descriptive analysis included actual frequencies, percentage, calculation of means, standard deviations (SD) of categorical variables. The statistical correlations between different determinants (demographic parameters and biochemical parameters) with HRQOL were analyzed using chi-square test, Mann-Whitney Test and Kruskal Wallis Test as appropriate. The values were considered statistically significant if P < 0.05.

RESULTS

Out of total 70 patients included in the study, only 60 could complete the whole study protocol including laboratory investigations and QOL questionnaire so only those were included in the analysis. Mean age of the study patients was 53.92 ± 9.27 with male preponderance and male: female ratio of 1.5:1. All the patients in the study suffered from type 2 diabetes and mean duration of the diabetes was 8.0±1.4 year. Mean BMI of the study patients was 23.36 ±1.4. Baseline demographic and biochemical parameters are shown in table 1. The blood sugar levels were found to be high in both male and female patients as per the WHO diagnostic criteria for diabetes with the mean FBS and PP2BS level of 162±92.8 and 249.3±67.6 respectively. Mean HBA1c level was 7.9±1.8 suggesting poor control of blood sugar over past 3 months contributing to diabetes foot ulcer. Levels of lipid profile and serum creatinine are also shown in table 1. All the patients of diabetes foot showed deteriorated quality of life with mean score of 42.2±15.13 in social domain, 17.12±7.43 in wellbeing, 75.33±27.06 in physical domain and total score of 146.56±45.46. Overall QOL perceived and satisfaction level was 10.62±3.01 suggesting not satisfying with their QOL. Association of the blood glucose related parameters with QOL scores are shown in table 2. Mean QOL score increased from 37.58±15.26 to 49.12±12.23 in social domain, from 16.89±4.51 to 19.33±4.75 in wellbeing, from 69.72±26.44 to 83.12±21.97 in physical symptoms, from 9.05±2.78 to 11.37±3.17 and overall score increased from 133.25±44.85 to 162.96±38.17 as FBS levels increases. FBS levels were found to be significantly affecting all the domains like social domain (p=0.03), wellbeing (p=0.049), physical domain (p=0.04) and overall quality of the life (p=0.04) and total HRQOL scores (p=0.009). PP2BS was not significantly affecting the QOL score at any domain in this study. HBA1c was also found to be affecting all the domains including social, wellbeing, physical symptoms score and overall quality and total score (p<0.05). As shown in table 3, other biochemical parameters also affect QOL scores. On analysing other laboratory parameters and their association with QOL scores, it was found that decrease Hb levels were significantly affecting social (p=0.023) domain, physical symptoms (p=0.014) and total score (p=0.059) of the patients. BMI levels were found to be significantly affecting social, physical symptoms, total scores and overall quality life (P<0.01). Total cholesterol levels and serum creatinine levels were not significantly associated with the QOL scores (p>0.05).

RESULTS

Table 1: Baseline characteristics of study patients: (n=60)

* According to ADA(American Diabetes Association)

 

Table 2: Blood glucose level related parameters and their association with QOL scores in diabetes foot ulcer patients:

Table 3: Other laboratory parameters and their association with QOL scores in diabetes foot ulcer patients (n=60)

 

DISCUSSION

Diabetes foot ulcers are difficult complication of DM requiring special attention. Successful healing of DFUs often requires long periods of treatment with additional limitations in patients' daily activities. This burden in the life of patients adversely affects Health-Related Quality of Life (HRQOL). Most significant parameter affecting healing of ulcer is glycemic control as mentioned in various literatures^7,9,10. Different biochemical and laboratory investigations are used to diagnose and monitoring of diabetes patients which can also serve as predictors for HRQOL. An understanding of the determinants of DFU patients' HRQOL may help health professionals in clinical decision making, specifying risk groups and allowing the prediction of the HRQOL. The aim of this study was to ascertain the association and impact of different biochemical parameters on health-related quality of life in patients with diabetic foot ulcers. The overall HRQOL scores suggests poor quality of life in patients with DFU in this study which is well coinciding with the literature suggesting poor quality of life in patients with complications of diabetes.^17,18 The study showed that there is derangement in the values of some biochemical parameters investigated in the T2DM cases having foot ulcers and it affects quality of the life of the patients. The blood sugar levels were found to be high in both male and female patients as per the WHO diagnostic criteria for diabetes. Poorly controlled PPBS levels have been shown to adversely affecting on arteries leading to either microvascular or macrovascular or both complications¹⁹. It independently shows association with disability and death caused by cardiovascular disease irrespective of FBS. In this study, only FBS levels not the PP2BS levels were found to be significantly affecting quality of life of the individuals. Most patients perceive that raised PP2BS is because of their food intake and they didn’t perceive its importance in diabetes management reflected as no correlation in this study. Through patients’ counselling should be done to improve their perception about glycemic control and its impact on HRQOL. Different studies have already described an association between higher levels of HbA1c and significantly lower HRQOL^20,21. Our study also found that exact same association between HRQOL and HbA1c levels. Tight glycemic control achieved over past 3 months may help in better ulcer healing and improve the mobility of the leg leading to improved quality of life. Moreover, glycemic control can delay the progression of diabetes neuropathy which can be important predictors in DFU healing. Another Brazilian study also showed the direct relationship between higher glycemic levels in patients who were more dissatisfied with Type 1 Diabetes mellitus²². One possible explanation would be that the patients felt uncomfortable when visualizing high glucose levels since hyperglycemia is well known to be associated with complications of the disease. It seems that mean glucose levels are more easily interpreted than HbA1c levels as an indicator of glycemic control. These biochemical parameters related to blood glucose levels measurements like FBS, PP2BS, HbA1c, mean glucose levels can act as effective predictors for the HRQOL which is considered as outcome of patients. However, the causal relationship between these variables remains unclear. HRQOL can affect a patient’s perception of the disease, its management, behavior related to self-care, metabolic control and the incidence of complications; all these variables, in turn, can affect the HRQOL^23,24. One can also speculate that hyperglycemia is directly associated with severe symptoms moreover patients with poor QOL adhere less to the treatment leading to hyperglycemia (as shown as higher mean FBS and PP2BS values in this study) and poor QOL. Further prospective and interventional studies are necessary to clarify the causality of this relationship. Previously, two studies have reported HRQOL in diabetes patients from Brazil including the large sample of type 1 diabetes patients. The first study evaluated a sample of patients younger than those in our study and demonstrated that a better glycemic control as achieved by HbA1C could positively impact the health status of individuals with Type 1 diabetes mellitus²⁵. A secondary analysis using the same population demonstrated differences in health status in different Brazilian regions; these differences, however, were not explained by HbA1c levels. The authors suggested that additional factors not evaluated in their study could determine theHRQOL of patients with Type 1 diabetes mellitus²⁶. It is worth noticing that SMBG was not evaluated in these studies. As found in our study with mean Hb level of 11.7 ± 1.6 gm/dl, occurrence of anaemia in patients with T2DM is a frequent condition^27,28. Anaemia is identified as an important predictor for microvascular disease ^[29] or progression of kidney diseases³⁰. Anaemia contributes to tiredness in 74% of the diabetic people than those without anaemia ^[31]. This could explain the significantly higher scores in physical symptoms domain of HRQOL in DFU patients in this study. Kidney function as evaluated by serum creatinine levels were not significantly found to be associated with any domain of HRQOL. We didn’t find significant association of serum total cholesterol with HRQOL in this study. Previous researchers have found that dyslipidemias are frequently associated with the T2DM and it is one of the major risk factors for cardiovascular diseases³². The elevated levels of triglycerides with low HDL levels when compared to normal ones showed an increased risk of coronary heart disease (CHD)^32] Sample size of our study was small to evaluate such detailed lipid profile analysis and its association with different parameters of the HRQOL. We found total WBC count slightly on the higher side in patients of DFU. They are mainly because of the foot ulcer with probable inflammatory response at the site in active ulcer patients. But higher values are little controversial in patients with healed diabetes foot ulcers. Previous studies have shown that T2DM has an impact on total and differential counts of WBC³³. Increased WBC count has been shown as independent biomarkers for macro and microvascular complications responsible for death and disability in T2DM patients. Lymphocyte count is decreased with the advancement of diabetic nephropathy even in the normal range¹⁹. The future incidence of CHD is predicted by the total and the differential cell counts of WBC (eosinophils, neutrophils, and monocytes) ^[19]. Role of WBC counts as predictors for HRQOL in DFU patients remains uncertain from the study. Further larger studies focusing on this aspect is required. This study has evaluated the role of different biochemical parameters for predictors of HRQOL in DFU patients but it has some limitations. First, only a small number of individuals were evaluated and that too from a single centre. It seems reasonable to speculate that different results would have been achieved with larger populations and longer follow-up. These two important limitations (i.e., sample size and study length) may also have impacted on the HRQOL in DFU patients. Also geographic variations affecting QOl could not be evaluated in this study.

 

CONCLUSION

HRQOL has been deteriorated all domains like social, well being, physical symptoms and overall quality of life in patients with diabetes foot ulcer as shown by increased scores in “Cardiff Wound Impact Questionnaire”. Different biochemical parameters found be associated with HRQOL in DFU patients and they can be used as predictors of HRQOL in DFU patients. Tight glycemic control as evaluated by FBS levels and HbA1c levels were significantly affecting HRQOL scores. Decrease haemoglobin and increased BMI levels were found to affect physical symptoms related quality of life in DFU patients. Management of diabetes patients should involve multifactorial approach involving diet and non-pharmacological measures, drug therapy, preventive foot care etc. aimed at achieving tight glycemic control as well as improvement in quality of life of the patients with DFUs.

 

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