Neuropathy and depressive disorders in people with diabetes as a public health challenge

INTRODUCTION

Diabetes mellitus is one of the most common civilization diseases affecting humankind [1]. Current data from the National Health Fund indicate that the number of people with diabetes in Poland is approximately 3 million, and it is estimated that in 2030, every tenth person will suffer from diabetes [2]. Long-term high blood glucose levels in diabetic patients can cause serious damage to the patients’ organs and bodies, resulting in chronic diabetic complications that develop gradually, leading to serious organ damage [3]. Chronic complications in diabetes include (a) diabetic macro- and micro-angiopathies, which damage blood vessels, causing impaired blood flow through malfunctioning blood vessels, leading not only to myocardial infarction but also to stroke [1]; (b) diabetic retinopathy, which damages the blood vessels of the retina and impairs the patient’s vision [4]; (c) cataracts, which arise as a consequence of damage to lens proteins [5]; (d) diabetic nephropathy, which damages the patient’s kidneys due to the removal of excessive amounts of fluid, glucose and protein from primary urine, with high arterial blood pressure [4]; (d) diabetic neuropathy, which damages the conduction of nerve impulses from the brain to the sense organs [6]; (f) gum and periodontal diseases, which, together with excessively developing bacteria in the oral cavity and high glucose concentration in saliva, attack tooth enamel, accelerating tooth decay, and subsequent damage to blood vessels intensifies gum infections [7]; (g) sexual dysfunctions in women [8]; (h) sexual problems in men resulting from erectile dysfunction leading to impotence [9]; and (i) diabetic foot resulting from a combination of micro- and macro-angiopathic changes, neuropathy and infections of skin lesions of the heel or toes. Injuries and mechanical damage to the skin of the toes and/or heel can lead to difficult-to-heal and painless wounds and ulcers due to a greater tendency for bacterial infections to occur [10]. Diabetic micro- and macro-angiopathy, along with diabetic neuropathy, lead to the development of diabetic foot, which, if left untreated or improperly treated, may result in severe infection of the deep tissues of the foot, ultimately leading to amputation [10].
Various chronic complications of diabetes often lead to the development of depressive states and depression in diabetic patients [11]. However, the most common chronic complication of diabetes is neuropathy, which develops due to metabolic disorders and changes in the nutritional vessels of the nerves, consequently leading to segmental demyelination and neuronal loss. Diabetic neuropathy can manifest either as generalized polyneuropathy (sensory, sensorimotor or autonomic) or as focal or multifocal neuropathy [12].
Patients often experience symptoms of diabetic neuropathy, especially severe pain, accompanied by tingling and burning, resulting in a reduction in quality of life [13-15]. Discomfort resulting from pain often leads to limitations in everyday activities and may also result in withdrawal from social activity, which in turn leads to mood disorders, forcing a change in the functioning of the individual in the area of emotions, cognition and behavior [16], as well as depressive disorders. It is estimated that depression is two to three times more common in people with diabetes, but most cases of depressive disorders remain undiagnosed [17].

MATERIAL AND METHODS

The research was conducted among patients of the Diabetology Clinic of the Institute of Rural Health by using a diagnostic survey method and tools, including an original survey questionnaire and the Beck Depression Inventory, the test for screening depression. The selection of the patients for the sample was nonrandom. The obtained survey results were associated with the results of the patients’ biochemical tests and the results of their medical examinations to look for symptoms of diabetic neuropathy. Single missing data in the research material collected for analysis resulted from missing medical records or omission of some questions by patients completing the survey questionnaire on their own. Therefore, the missing data were excluded from the statistical analysis. Calculations were made using the program IBM SPSS Statistics 25. This research was carried out as part of a scientific project financed by a subsidy from the Ministry of Science and Higher Education entitled “Sociodemographic determinants of depressive disorders in people with diabetic neuropathy”. The project received positive approval from the Bioethics Committee of the Institute of Rural Health (decision no. 6/2016). The research was carried out during 2017-2019. Participation in the research was voluntary and was preceded by the patients providing informed consent. In total, 314 patients from the Diabetology Clinic of the Institute of Rural Health participated in the present study.

RESULTS

CHARACTERISTICS OF THE STUDIED PATIENTS

The analyzed social factors included age, gender, place of residence, education and marital status, professional status and financial situation.
Women were the leading percentage of respondents (60.5%), and men accounted for 39.5%. The dominant age category was patients aged 51-70 years (48.7%), and the remaining age categories were ≥ 30 years (11.1%), 31-50 years (28.0%), and < 70 years (12.1%).
The average age of the patients was 53.23 ± 16.03 years. The average ages of the women and men were similar, at 53.83 ± 16.33 years and 52.31 ± 15.57 years, respectively.
Most of the patients included in the study were urban residents (63.1%), and the rest lived in rural areas (36.9%). Every fourth study participant had a higher education (25.8%). The remaining respondents had the following education level: postsecondary or secondary (44.6%), basic vocational (22.3%) or primary (7.3%).
Most of the surveyed patients were married (57.3%), and the rest were single (18.5%), widowed (16.9%), or divorced or separated (7.4%).
More than half of the surveyed patients were economically inactive (60.7%). The financial situation was assessed by most respondents as bad or average (75.2%), and only 24.8% of respondents described it as good.

TYPE OF DIABETES AND DURATION OF DISEASE

The study participants included patients with two types of diabetes. More than half of the participants had type 2 diabetes (58.3%), and the rest (41.7%) had type 1 diabetes. The analysis of the disease duration revealed that 35.3% of the patients had diabetes for 1-10 years, 36.8% for 11-20 years, and 27.9% for 21 years or more, with an average duration of 17.5 ± 11.59 years in people with type 1 diabetes and 15.1 ± 8.67 years in people with type 2 diabetes.

SELECTED ASPECTS OF HEALTH

Table 1 presents selected aspects of the health status of the surveyed patients.
The height and weight of the examined patients were measured, which allowed for the determination of the body mass index (BMI). It was assumed that BMI < 18.5 means underweight, 18.5 ≤ BMI ≤ 24.9 normal weight, 25 ≤ BMI ≤ 29.9 overweight and BMI > 30 obesity. Analysis of the BMI of the study patients revealed that 76.3% of them were overweight or obese, 22.8% had a normal body weight, and 1% were underweight. Obesity was significantly more common in patients with type 2 diabetes (80.2%) than in people with type 1 diabetes (13.8%). In turn, patients with type 1 diabetes were significantly more likely to be overweight than were those with type 2 diabetes (37.7% vs. 13.7%) (χ² = 139.717, p = 0.000).
The level of glycated hemoglobin (HbA_1c) was determined for the study participants. According to the recom­mendations of the Polish Diabetes Association, in patients diagnosed with diabetes, it is recommended that the HbA_1c level should be lower than 7%, which will minimize the risk of complications of this disease. In our studies it was assumed that a level above 6.5% should be an indication to modify the treatment so that this value does not exceed 7%. Based on these guidelines, it was assumed that HbA1c values less than 6.1% are below the norm, values 6.1-6.5% are the norm, and values greater than 6.5% are above the norm. The research showed that in the vast majority of patients (90.5%), the HbA1c value was above the upper limit of the normal range, < 6.1% represented 6.2% of the respondents, and 6.1-6.5% represented 3.3% of the studied patients.
Based on medical records, it was established that the vast majority of both type 1 and type 2 diabetes patients had 4 or more insulin injections per day (72.5% and 78.7%, respectively). Every fourth patient with type 1 diabetes used an insulin pump.
Patients struggle with various complications of diabetes, often several at the same time (micro- and macro­vascular). Due to the main aim of the study, the focus was primarily on diabetic neuropathy and depressive disorders. Most patients (64.0%) experienced complications of diabetic neuropathy.
Logistic regression analysis was used to identify the determinants of diabetic neuropathy. In the theoretical model, the dependent variable is the dichotomous variable of the occurrence of neuropathy (0 – no, 1 – yes). Eight independent variables were introduced into the model using the backward Wald selection technique, in the order from variables determining selected indicators of the health status of the respondents to demogra­phic variables: HbA1c level (exact measurement), type 1 diabetes (0 – no, 1 – yes), insulin use (0 – no, 1 – yes), BMI incorrect (0 – no, 1 – yes), number of years of diabetes (number of years with an accuracy of 1 year), sex (1 – woman, 2 – man), place of residence (1 – rural area, 2 – city), education (1 – low [primary, basic vocational], 2 – secondary, 3 – higher) (Table 2).
Logistic regression analysis for the model of neuropathy determinants identified 4 variables that significantly influenced the probability of developing this disease: HbA1c level, occurrence of type 1 diabetes, number of years of suffering from diabetes, and education level (the reference category was low education). The analysis showed that an increase in the HbA1c level by one unit increased the probability of neuropathy by 16.2% (odds ratio = 1.162; Table 2). The likelihood of developing this disease also increases with the number of years of diabetes. Increasing the duration of the disease by 1 year increased the probability of developing neuropathy by 8% (odds ratio = 1.08). The probability of developing neuropathy was reduced by almost 80% in the group of people with type 1 diabetes compared to those with type 2 diabetes (odds ratio = 0.215; Table 2). Moreover, the probability of developing this disease decreased by 63.6% in the group of people with higher education compared to people with lower education (odds ratio = 0.364; Table 2).
The presented model was statistically significant (χ² = 76.6982; p < 0.001). The value of Nagelkerke’s R² coefficient = 0.307 means that the correlation found within the model is moderate and explains approximately 30% of the variance. The results of the Hosmer and Lemeshow test (χ² = 8.087; p = 0.425) indicate that the empirical data are well suited to the predicted data. We can therefore assume that the model fits the data well.
Depressive disorders are a common consequence of diabetes. The analysis of the results showed that every second patient was experiencing such disorders, and they were of varying severity (Table 1). At the same time, it is worth mentioning that depressive disorders were diagnosed significantly more often (χ² = 11.23, df = 3, p = 0.011) among patients with type 2 diabetes (57.4%) than among patients with type 1 diabetes (43%).
Similarly to the factors determining the occurrence of diabetic neuropathy, logistic regression analysis was used to develop a model to predict the occurrence of depressive disorders (Table 3). The dependent variable in the model was the dichotomous variable occurrence of depression (1 – no, 2 – yes), while the independent variables were entered into the model in two groups. The first was related to selected health status indicators, and the second was sociodemographic variables, such as age, place of residence, level of education, marital status, professional activity, and financial situation. The analysis identified 4 variables that significantly influence the probability of developing depressive disorders, i.e., BMI, the occurrence of neuropathy, the financial situation of the respondents, and their professional activity.
Statistical analysis using a logistic regression model showed that there is a relationship between the occurrence of depressive disorders in diabetic patients, diabetic neuropathy and BMI; therefore, it should be assumed that neuropathy, overweight and obesity are risk factors for depression. For people diagnosed with neuropathy, the risk of depression increased by 57.7%, while an increase in BMI of one unit increased the risk of depressive disorders by 2.9% (Table 3). As previously mentioned, sociodemographic variables were also included in the model. The analysis showed that two of the previously indicated variables are related to the occurrence of depressive disorders, namely, financial situation and professional activity. It was assumed that the reference cate­gory for the financial situation was its average assessment. Having a poor financial situation compared to the average increases the probability of depression by 50.4% (odds ratio = 1.504). A good financial situation has the opposite effect, which in turn reduces the risk of depression by 44.0% compared to the average. The probability of depression was reduced by 37.2% for professionally employed people (odds ratio = 0.628) (Table 3).
As mentionjavascript: ve.execCommand('formBodyId', 'veSub', '');ed above, diabetic neuropathy is an important predictor of increased risk of developing depressive disorders. Studies have shown a statistically significant relationship between the occurrence of depressive disorders of varying severity in patients and the occurrence of diabetic neuropathy, especially in relation to mild depressive disorders (Table 4).
The surveyed patients were asked about their need for professional psychological support. It was reported by 44.3% of people surveyed. Notably, 69.4% of patients also declared the need to expand their knowledge about diabetes and the treatment process, which supports the value of conducting educational activities for this group of patients.

DISCUSSION

Diabetic neuropathy is one of the most common causes of chronic and highly disabling neuropathic symptoms and is a complication of diabetic microangiopathy. The results of the present study showed that there is a relationship between the impact of health and social factors and the occurrence of neuropathy and depressive disorders in people with diabetes. Factors increasing the risk of neuropathy include increased HbA_1c levels and type 2 diabetes. A similar relationship was detected by other authors [19-23]. A factor significantly increasing the risk of neuropathy was the duration of the disease. It was found that extending the duration of the disease by another year increases the probability of developing neuropathy by 8%. This predictor was also found to strongly increase the probability of occurrence of the discussed complication in studies carried out by other scientists [24, 25].
Among the social variables that predispose patients to neuropathy, logistic regression analysis revealed that the patient’s education level may be associated with increased or decreased risk of this complication. The relationship observed in this analysis showed that the probability of neuropathy is 63.6% lower in the group of people with higher education compared to people with lower education. Similar conclusions were reached by researchers from China, who found that a higher level of education was a protective factor compared to patients with a primary school education or less [25, 26]. Although other health disorders and illnesses are also associated with diabetic neuropathy, this study focused primarily on depressive disorders.
Type 2 diabetes increases the risk of depression and may contribute to a more serious course of the disease [27, 28]. Moreover, depression may increase the risk of progression from prediabetes to type 2 diabetes [29] and the subsequent risk of hyperglycemia, insulin resistance, and micro- and macrovascular complications [27].
It was confirmed in this study that among the factors that had a significant impact on the occurrence of depression in diabetic patients were a BMI that deviated from the norm, accepted as appropriate, and the occurrence of diabetic neuropathy, confirmed by a medical examination. A similar relationship has been confirmed by other authors [30, 31]. However, in this study, the increase in the risk of depression was also estimated. Statistical analyses revealed that neuropathy increases this risk by 57.7%, and an increase in BMI of 1 unit increases the risk of depression by 2.9%.
It has also been found that social factors are related to the occurrence of depressive disorders. Studies using logistic regression analysis have shown that a good financial situation and being professionally active among people with diabetes are factors that reduce the risk of deve­loping depressive disorders. Similar findings have been reported in studies by other authors. More specifically, in the study by van Duinkerken et al. [32], the factors increasing the risk of depressive episodes among people with diabetes (selected on the basis of multinomial logistic regression) included financial problems, age and female sex, lower education, experiencing discrimination at work, home and school, larger waist circumference, albumin to creatinine ratio and insulin resistance, as well as the presence of hypertension and cardiovascular disease.
On the other hand, a biopsycho-metaanalysis of social and nutritional factors of depression in patients with type 2 diabetes based on the results contained in 71 articles showed that among the social factors significantly increasing the risk of depression were low economic and social status but also poor social support, low educational status, and marital status single/no partner [33].
Knowing that a significant number of patients with diabetes suffer from depression or stress related to diabetes, and most of them remain undiagnosed and untreated, it seems well justified to conduct routine screening for depression and distress [34]. The presence of depression combined with other ailments leads to a significant reduction in the quality of life of patients with diabetes [35], which in turn requires psychological intervention. Almost half of the people surveyed stated that they felt the need for professional support.
In summary, the diabetes epidemic in the 21^st century and its accompanying complications are important challenges for public health, especially in the areas of health education, health promotion and prevention, and in terms of reducing health inequalities resulting from socioeconomic conditions.

CONCLUSIONS

1. Research has shown that diabetic neuropathy and depressive disorders are important disease consequences of diabetes, the occurrence of which is determined by both health and social factors.
2. The occurrence of neuropathy was found in 2/3 of the study patients. The factors increasing the risk of this complication include increased levels of glycated hemoglobin, type 2 diabetes, and an increasing number of years with the disease. At the same time, it was found that higher education was a factor reducing the risk of diabetic neuropathy.
3. Depressive disorders affected more than half of the examined patients, and the factors increasing the risk of their occurrence included diabetic neuropathy, type 2 diabetes, high BMI, professional inactivity and poor financial situation.
4. In the face of the growing number of people suffering from type 2 diabetes, it is advisable to conduct educational activities to promote knowledge about the risk factors for diabetes and its complications.

DISCLOSURE

The authors report no conflict of interest.

References