|Year : 2022 | Volume
| Issue : 2 | Page : 130-136
Comparison of oxidative stress status and quality of life in participants with type 2 diabetes mellitus according to treatment modality
O Kuet1, TP Kilit1, E Kocak2
1 Department of Internal Medicine, Faculty of Medicine, Kutahya Health Science University, Kutahya, Turkey
2 Department of Medical Biochemistry, Faculty of Medicine, Kutahya Health Science University, Kutahya, Turkey
|Date of Submission||23-Feb-2020|
|Date of Acceptance||19-Oct-2021|
|Date of Web Publication||16-Feb-2022|
Dr. T P Kilit
Department of Internal Medicine, Kütahya Health Sciences University, 43050, Kütahya
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Oxidative stress triggered by hyperglycemia in diabetic patients leads to macrovascular and microvascular complications, resulting in deterioration in the quality of life. Aims: This study aimed to compare the oxidative stress status and quality of life in participants with type 2 diabetes mellitus according to treatment modality. Patients and Methods: Ninety type 2 diabetes mellitus participants aged between 40 and 60 years were included in the study. Forty-five participants were receiving oral antidiabetic drugs and 45 participants were receiving insulin therapy. Total antioxidant status, total oxidant status, and paraoxonase-1 were measured and oxidative stress indices were calculated. The SF-36 quality of life questionnaire was applied to the participants. Results: The total oxidant status and oxidative stress indices values were higher in the insulin-treated group than in the group treated with oral antidiabetic drugs. Paraoxonase-1 activities of the oral antidiabetic drugs-treated group were statistically significantly higher than the insulin-treated group. In the oral antidiabetic drugs-treated group, the physical function, social function, and pain subscale scores were higher than that of the insulin-treated group. In all participants, a negative correlation between total antioxidant status and fasting blood glucose and hemoglobin A1c, a positive correlation between total oxidant status and hemoglobin A1c and triglyceride, and a positive correlation was found between oxidative stress indices and fasting blood glucose and hemoglobin A1c. Conclusions: It was found that oxidative stress parameters were higher and quality of life was worse in the insulin-treated participants than participants treated with oral antidiabetic drugs. These results may be closely related to more severe chronic complications in insulin-dependent diabetes.
Keywords: Diabetes mellitus, hypoglycemic agents, insulin, oxidative stress, quality of life
|How to cite this article:|
Kuet O, Kilit T P, Kocak E. Comparison of oxidative stress status and quality of life in participants with type 2 diabetes mellitus according to treatment modality. Niger J Clin Pract 2022;25:130-6
|How to cite this URL:|
Kuet O, Kilit T P, Kocak E. Comparison of oxidative stress status and quality of life in participants with type 2 diabetes mellitus according to treatment modality. Niger J Clin Pract [serial online] 2022 [cited 2022 Dec 2];25:130-6. Available from: https://www.njcponline.com/text.asp?2022/25/2/130/337773
| Introduction|| |
Oxidative stress is associated with both the pathogenesis of diabetes and the complications of diabetes. The antioxidant capacity measurement may be useful in assessing oxidative stress and predicting the risk of complications in individuals with diabetes.
It is known that the imbalance between the body's antioxidant defense mechanism and the rate of free radical formation during the course of diabetes is known to cause tissue damage. High blood glucose in participants with diabetes leads to the formation of free radicals that can cause protein glycation, glucose auto-oxidation, and lipid peroxidation. Among other potential mechanisms of oxidative stress, there is a lack of antioxidant defense systems. As a result, chronic complications occur in participants with DM.
Oxidant and antioxidant systems are in balance in the body. It has been shown in previous studies that total antioxidant status (TAS) provides information about the status of all antioxidants in the body and total oxidant status (TOS) provides information about the oxidant system in the organism.
Paraoxonase-1 (PON-1) is a glycoprotein structure esterase that hydrolyses lipid peroxides and contains 355 amino acids bound to high-density lipoprotein (HDL). It has been shown that PON-1 is present in the structure of HDL and low-density lipoprotein (LDL) phospholipids have a protective role against oxidation by preventing lipid peroxidation. Serum PON-1 activity is low in participants with a high risk of atherosclerosis, such as DM. Thus, it is thought that coronary artery disease (CAD) seen in DM may be due to the decrease in PON-1 activity.
The rate of psychiatric symptoms and illness is higher in participants with DM compared with healthy individuals. Emotional reactions, adaptation difficulties, and depressive disorders are the most common mental problems in participants with DM. These psychiatric symptoms and disorders lead to noncompliance in treatment and difficulty in metabolic control. As a result, the frequency of the development of chronic complications of DM increases. In the studies, it was emphasized that quality of life was associated with hyperglycemia, insulin therapy, duration of diabetes, age, gender, diabetes complications, and the presence of other comorbidities.
It is thought that lifestyle change, compliance with treatment, and strict glycemic control can prevent complications in participants with DM and oxidative stress can be reduced with appropriate treatment. If the disease itself and its complications are kept under control, it can be prevented from adversely affecting the quality of life.
This study aimed to compare the effects of treatment modalities in type 2 DM on oxidative stress conditions and quality of life that may cause chronic complications.
| Subjects and Methods|| |
In this observational cross-sectional study, 90 type-2 diabetes mellitus participants aged between 40 and 60 years were included. A simple random sampling technique was used to select the study participants. Forty-five participants were receiving oral antidiabetic drugs and 45 participants were receiving insulin therapy. Pregnant women, participants with comorbid disease (malignancy, cerebrovascular disease, CAD, etc.), participants with active infection, participants using vitamins and similar antioxidant supplements, smokers, and alcohol users were excluded from the study. Before the study, approval was obtained from the local medical ethics committee with the decision number 2015/07-166. Informed consent was obtained from participants in the study.
Short form 36 quality of life questionnaire (Short form-36; SF-36)
SF-36 quality of life questionnaire, which was developed by Rand Corporation and which was a generic criterion self-assessment scale was performed for all participants to evaluate their quality of life. The SF-36 quality of life questionnaire is used to measure the quality of life, especially in participants with physical illness. It can evaluate its positive aspects as well as its negative health and is very sensitive to detect small changes in disability. SF-36 examines the physical function, role limitations (due to physical and emotional problems), social function, mental health, vitality (energy), pain, and eight dimensions of health in 36 items. The scale does not have a raw score and only the total score of eight subdimensions is calculated. The scores of the subscales ranged from zero to 100. Zero indicates poor health and 100 indicates good health. It is not possible to calculate the total score of the scale. The validity and reliability study of the Turkish version was conducted by Demiral et al.
Blood sample collection and laboratory analysis
Venous blood samples were collected from the participants for 12 h after fasting for routine biochemical diabetes tests and oxidative stress parameters and whole blood samples were collected for glycated hemoglobin (HbA1c) measurements. After blood samples were taken, they were centrifuged within 1 h and the serum samples were divided into polystyrene tubes. Fasting blood glucose and lipid parameters (total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride) were measured on the Beckman Coulter AU680 analyzer (Beckman Coulter, Miami, FL, USA) using the original kits without waiting on the day of blood taken. HbA1c values were measured by the high-pressure liquid chromatography (HPLC) method on the Tosoh G8 HPLC analyzer (Tosoh Bioscience, Inc., San Francisco, CA). Serum samples for TAS, TOS, and PON-1 were stored at −80°C until the day of study. Serum TAS and TOS levels and PON-1 activities were measured according to the method developed by Erel on a Beckman Coulter AU680 analyzer (Beckman Coulter, Miami, FL, USA) using commercial kits (Rel Assay Diagnostic, Bursa, Turkey).,, TAS levels were expressed as mmol Trolox equivalent/L, TOS levels were expressed as μmol H2O2 equivalent/L, and PON-1 activity was expressed as U/L.
Calculation of oxidative stress index (OSI)
The percent ratio of TOS to TAS was accepted as the OSI, an indicator of the degree of oxidative stress. TAS in mmol Trolox equivalent/L was converted to μmol Trolox equivalent/L, after which the OSI was calculated as follows: OSI = [(TOS, μmol H2O2 Eq/L)/(TAS, μmol Trolox Eq/L) × 100]. Results were expressed as arbitrary units (AU).
Statistical analyses were performed using GraphPad version 6.05 (GraphPad Software, Inc., CA, USA). All data were tested for normality using the Kolmogorov–Smirnov test. Data showing normal distribution were shown as means ± SD (standard deviation) and data not normally distributed were shown as the median and interquartile range (IQR) (25%–75%). According to the distribution of data, parametric or nonparametric statistical tests were used. In the comparison of the variables examined between the study groups, data showing normal distribution were analyzed by two-tailed Student's t-test and data without normal distribution were analyzed by Mann–Whitney U test. Correlation analyses were performed using Spearman's correlation analysis because variables were not normally distributed in all groups. P < 0.05 values were considered statistically significant; no adjustment was made for the multiplicity of statistical tests.
| Results|| |
Fifty-one of the participants were women (57%) and 39 were men (43%). The mean age of the participants was 52.1 ± 4.9 years (age range = 40–60 years). When the demographic data, biochemical, and oxidative stress parameters of the study groups were compared, the median duration of DM in the insulin-treated group was 10 years (IQR: 4.5–13.5 years), and the median of the group receiving OAD was 5 years (IQR: 3–7 years), and a statistically significant difference was found between the groups (P = 0.001) [Table 1]. Although the median HbA1c of the OAD group was 58 mmol/mol (IQR: 46–76 mmol/mol), it was higher than 73 mmol/mol (IQR: 57–91 mmol/mol) of the insulin-treated group and there was a statistically significant difference between them (P = 0.003). When the TOS values of the two groups were compared, the median TOS of the OAD group was 3.52 μmol H2O2 Eq/L (IQR: 3.02–4 μmol H2O2 Eq/L), and the median of the insulin receiving group was 3.94 μmol H2O2 Eq/L (IQR: 3.67–4.7 μmol H2O2 Eq/L), the difference between the groups was statistically significant (P < 0.001). The mean values of the calculated OSI values were 0.23 ± 0.05 in the OAD group and 0.29 ± 0.07 in the insulin-receiving group and there was a statistically significant difference between them (P < 0.001). When the PON-1 values were compared between the groups, the median OAD group was 365 U/L (IQR: 183–531 U/L), and the insulin-treated group was 192 U/L (IQR: 123.5–385 U/L). There was a statistically significant difference between the groups (P = 0.007). When the gender, age, weight, height, FBG, triglyceride, total cholesterol, HDL, LDL, and TAS values of the two groups were compared, no statistically significant difference was found.
|Table 1: Comparison of demographic data and biochemical parameters between study groups|
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When the SF-36 quality of life questionnaire scores was compared between the groups, the median physical function scores of the OAD group was 83.0 (IQR: 63.0–91.5), and the median of the insulin-treated group was 63.0 (IQR: 50.0–80.0), and a significant difference was found between groups (P < 0.001) [Table 2]. The median social function score of the OAD group was 70 (IQR: 50–100), whereas the insulin group received 50 (IQR: 30–75), and there was a statistically significant difference between the groups (P = 0.003). In the pain category, the median OAD group was 81 (IQR: 63–100), whereas the mean insulin group was 63 (IQR: 49.5–81.0) and there was a statistically significant difference between them (P = 0.003). When the scores of general health status, physical role difficulty, vitality, mental health, and emotional role difficulty categories were compared, no statistically significant difference was found between the groups.
When the relationship between oxidative stress parameters and biochemical parameters of all study participants was examined, a negative correlation was found between TAS and FBG and HbA1c (r: −0.25, P = 0.02 and r: −0.26, P = 0.01) [Table 3]. There was a positive correlation between TOS and HbA1c and triglyceride levels (r: 0.23, P = 0.03 and r: 0.23, P = 0.03). There was a positive correlation between the calculated OSI values and FBG and HbA1c values (r: 0.29, P = 0.005 and r: 0.34, P = 0.001). There was no significant correlation between PON-1 and other parameters.
|Table 3: Relationship between oxidative stress parameters and biochemical parameters|
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When the relationships between SF-36 questionnaire scores, demographic data, and biochemical parameters of the participants were examined, there was a negative correlation between vitality and total cholesterol and HDL (r: −0.25, P = 0.02 and r: −0.25, P = 0.02), negative correlation between mental health and HDL (r: −0.25, P = 0.02), negative correlation between mean age and FBG (r: −0.23, P = 0.03), negative correlation between mean weight and FBG (r: −0.23, P = 0.03), but there was a positive correlation (r: 0.23, P = 0.03) between weight and triglycerides [Table 4]. There was a negative correlation between height and HDL (r: −0.24, P = 0.02). There was a positive correlation between DM duration and FBG and HbA1c (r: 0.33, P = 0.002 and r: 0.29, P = 0.005, respectively). There was no statistically significant correlation between the other parameters.
|Table 4: Relationship between SF-36 questionnaire scores, demographic data, and biochemical parameters|
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When the relationships between SF-36 questionnaire scores, demographic data, and oxidative stress parameters were examined, a negative correlation was found between social function and TOS (r: −0.24, P = 0.02), a positive correlation was found between age and TAS (r: 0.39, P < 0.001), a negative correlation was found between age and OSI (r: −0.30, P = 0.004) [Table 5]. There was no statistically significant correlation between the other parameters.
|Table 5: Relationships between SF-36 questionnaire scores, demographic data, and oxidative stress parameters|
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| Discussion|| |
Oxidative stress is caused by an imbalance between the rate of formation of free radicals in the organism and their rate of elimination. When the rate of formation of free radicals exceeds the antioxidant capacity, the harmful effects of these substances on the organism begin to emerge. On the other hand, the importance of DM increases due to the role of oxidative stress in both the pathogenesis and chronic complications of the disease.
There are many studies in the literature on DM and oxidative stress. In these studies, some researchers investigated oxidative stress in participants with chronic complications of diabetes, and some researchers compared participants with diabetes and without chronic complications with healthy controls. When oxidative stress parameters were analyzed, statistically significant results were obtained.
In this study, considering the previous studies, two DM groups were compared because it was predicted that oxidative stress parameters would be high in DM groups compared with the healthy control group. According to the treatment received by participants with DM without chronic complications other than known HT, the participants were divided into two groups as OAD-treated and insulin-treated and their oxidative stress status was examined. When 45 participants using OAD and 45 participants receiving insulin treatment were compared in terms of oxidative stress parameters, in the insulin-treated group, TOS and calculated OSI were found to be higher and PON-1 was lower than the OAD group. In addition, DM duration and HbA1c levels were higher in the insulin-treated group than in the OAD group. This study demonstrated that longer DM duration and higher hyperglycemia in the insulin-treated group may have played a role in increased oxidative stress.
The PON level was found to be statistically lower in participants with DM using insulin than those using OAD. The difference from the other studies was that both groups were consisted of participants with diabetes and did not have any known DM complications.
The correlation analysis revealed a statistically significant negative correlation between TAS and FBG and HbA1c, a statistically significant positive correlation between TOS and HbA1c and triglyceride, and a positive correlation between OSI and FBG and HbA1c in all study participants. It can be concluded that poor glycemic control will adversely affect oxidative stress. In other words, the higher the plasma glucose and HbA1c averages, the greater the oxidant status. However, there was no statistically significant correlation between PON-1 levels and FBG, HbA1c, and lipid profile evaluated in this study.
Ultraviolet rays, drugs, lipid oxidation, radiation, aging, stress, smoking, and alcohol are among the factors affecting oxidative stress. It is known that oxidative stress increases with the aging process. Criteria such as the absence of chronic complications of diabetes, no signs of active infection, absence of any other chronic disease, and no advanced age were sought in the participants included in this study. The inclusion criteria of the participants are among the strengths of this study in terms of the parameters to be investigated.
The incidence of psychiatric disorders in participants with DM and the problem of treatment adherence, as well as an increase in diabetes complications, are observed. In this study, when 45 participants using OAD and 45 participants receiving insulin treatment were compared in terms of the results of the SF-36 quality of life questionnaire, physical function, social function, and pain subscales were statistically significantly lower in the insulin group compared with the OAD group. In the correlation analysis, it was found that there was a negative correlation between social function and TOS that could be clinically significant.
The quality of life of patients with diabetes is lower than the general population. When the subscales of the SF-36 quality of life questionnaire were compared in both groups, it was observed that the participants using insulin in the field of physical function, social function, and pain had lower scores. Considering that the DM duration of the insulin group was longer than the OAD group, it was concluded that the quality of life of the participants deteriorated during the illness. In addition, the fact that participants who inject at least one single dose of subcutaneous insulin per day had a lower mean score in the area of pain than participants receiving OAD suggests that subcutaneous injection adversely affects the quality of life.
In this study, a negative correlation was found between TOS and social function, which is one of the subscales of the SF-36 quality of life questionnaire. There were no clinically significant differences between the other subscales of the questionnaire and oxidative stress parameters.
| Conclusion|| |
In this study, when participants with diabetes who were not previously known to have chronic disease other than HT and were taking OAD and insulin treatment were compared in two groups, it was found that oxidative stress parameters were higher and quality of life was worse in an insulin-treated group than OAD group. It is thought that these results may be closely related to more severe chronic complications of insulin-dependent diabetes.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Opara EC, Abdel-Rahman E, Soliman S, Kamel WA, Souka S, Lowe JE, et al
. Depletion of total antioxidant capacity in type 2 diabetes. Metabolism 1999;48:1414-7.
Satoh M, Fujimoto S, Haruna Y, Arakawa S, Horike H, Komai N, et al
. NAD (P) H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy. Am J Physiol Renal Physiol 2005;288:F1144-52.
Wu R, Feng J, Yang Y, Dai C, Lu A, Li J, et al
. Significance of serum total oxidant/antioxidant status in patients with colorectal cancer. PLoS One 2017;12:e0170003. doi: 10.1371/journal.pone. 0170003.
Deakin SP, James RW. Genetic and environmental factors modulating serum concentrations and activities of the antioxidant enzyme paraoxonase-1. Clin Sci (Lond) 2004;107:435-47.
Sanghera DK, Saha N, Aston CE, Kamboh MI. Genetic polymorphism of paraoxonase and the risk of coronary heart disease. Arterioscler Thromb Vasc Biol 1997;17:1067-73.
Eren I, Erdi O, Sahin M. The effect of depression on quality of life of patients with type II diabetes mellitus. Depress Anxiety 2008;25:98-106.
Keinanen-Kiukaanniemi S, Ohinmaa A, Pajunpaa H, Koivukangas P. Health related quality of life in diabetic patients measured by the Nottingham Health Profile. Diabet Med 1996;13:382-8.
Bowling A, Bond M, Jenkinson C, Lamping DL. Short Form 36 (SF-36) Health survey questionnaire: Which normative data should be used? Comparisons between the norms provided by the Omnibus Survey in Britain, the Health Survey for England and the Oxford Healthy Life Survey. J Public Health Med 1999;21:255-70.
Demiral Y, Ergor G, Unal B, Semin S, Akvardar Y, Kivircik B, et al
. Normative data and discriminative properties of short form 36 (SF-36) in Turkish urban population. BMC Public Health 2006;6:247.
Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9.
Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11.
Eckerson HW, Wyte CM, La Du BN. The human serum paraoxonase/arylesterase polymorphism. Am J Hum Genet 1983;35:1126-38.
Yang H, Jin X, Kei Lam CW, Yan SK. Oxidative stress and diabetes mellitus. Clin Chem Lab Med 2011;49:1773-82.
Ceriello A, Bortolotti N, Pirisi M, Crescentini A, Tonutti L, Motz E, et al
. Total plasma antioxidant capacity predicts thrombosis-prone status in NIDDM patients. Diabetes Care 1997;20:1589-93.
Viña J, Borrás C, Miquel J. Theories of ageing. IUBMB Life 2007;59:249-54.
Güldal Altunoğ E, Sarı Z, Erdenen F, Müderrisoğlu C, Ülgen E, Sarı M. The relationship of depression, anxiety, and disability with HbA1c and duration of diabetes in patients with type 2 diabetes mellitus. Istanbul Med J 2012;13:115-9.
Rubin RR, Peyrot M. Quality of life and diabetes. Diabetes Metab Res Rev 1999;15:205-18.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]