The relationship between microvascular complications and depression in patients with type 2 diabetes mellitus who use insulin İnsülin kullanan tip 2 diabetes mellitus hastalarında mikrovasküler komplikasyonlar ile depresyonun ilişkisi

J Clin Exp Invest www.jceionline.org Vol 4, No 1, March 2013 1 Department of Endocrinology, School of Medicine, Harran University, Şanlıurfa, Turkey 2 Department of Internal Medicine, School of Medicine, Harran University, Şanlıurfa, Turkey 3 Department of Psychiatry, School of Medicine, Harran University, Şanlıurfa, Turkey Correspondence: Mehmet Ali Eren, Department of Endocrinology, Harran University Faculty of Medicine, Şanlıurfa, Turkey Email: drmalieren@hotmail.com Received: 04.12.2012, Accepted: 08.01.2013 Copyright © JCEI / Journal of Clinical and Experimental Investigations 2013, All rights reserved JCEI / 2013; 4 (1): 34-39 Journal of Clinical and Experimental Investigations doi: 10.5799/ahinjs.01.2013.01.0230


INTRODUCTION
Type 2 Diabetes Mellitus (DM) is a chronic and progressive disease during which microvascular complications such as nephropathy, neuropathy and retinopathy may develop. 1,2As is the case in other chronic diseases, the frequency of anxiety and depression increases in Type 2 DM. 3,46][7] The presence of depression is thought to complicate the glycemic control by disrupting the harmony between diet, exercise and therapy. 8Besides studies suggesting a correlation between the level of HbA1c, a good marker of glycemic control, and depressive symptoms, there are some which point to the contrary. 9 our study, we investigated the impact of diabetic microvascular complications on the frequency and severity of depression in Type 2 DM cases.

METHODS
Cases under the age of 65 admitted to our Endocrinology clinic, which had been using insulin for the past 6 months and/or more, were enrolled in this study.The study was approved by Harran University ethics committee.After informing patients about the study, their verbal and written consents were collected.Patients who had been diagnosed with depression or those who received anti-depressant therapy within the past 6 months were excluded from the study.For the determination of diabetic nephropathy, the spot urine albumin-creatinine ratio was measured in the first morning urine.Cases with a serum creatinine level of >1.4 mg/dl were excluded from the study.Detailed examination of the retina with an ophthalmoscope was performed for the determination of diabetic retinopathy.The presence and severity of diabetic neuropathy was defined by the "United Kingdom neuropathy screening score" (UKNS) as normal, mild, moderate and severe.The severity of the depression symptoms was assessed by the "Beck depression scale" (BDS).

Statistical analysis
SPSS version 15.0 (Windows, Chicago, IL, USA) was used for statistical analyses.Results were given as average ± standard deviation (SD).Categorical variants were compared via the Chi-squared test whereas the continuous variants were compared via the unpaired Student's t or Mann-Whitney U tests according to their compatibility with normal distribution.One-way ANOVA was used for the comparison between parametric data between three or more groups, and the Turkey test was used as the post hoc test.In the comparison between three or more groups, Kruskal-Wallis variation analysis was used along with the Mann-Whitney U test for sub group comparisons of the obtained results.Spearman correlation test was used in correlation analysis.p<0.05 was considered to be statistically significant.

RESULTS
An overall number of 80 Type 2 DM patients were included in the study.The groups were found to be biochemically similar (Table 1 and Table 2).Depression severity determined by the BDS showed significant increase going from group 1 to group 4 (p<0.001between all groups).Furthermore, as going from group 1 to group 4 according to the UKNS, there was an increase in the ratio of patients with moderate neuropathy (8.3% for group 2, 26% for group 3, 8.3% for group 4) or in the ratio of patients with severe neuropathy (4.2% for group 2 and 33.3% for group 4) (p<0.001).In the Spearman correlation analysis, there was a positive correlation between the severity of the depression determined by the BDS and triglyceride (TG) (r=0.235,p=0.036) and the UKNS (r=0.231,p=0.039) (Figure 1, Figure 2).No correlation was found between the presence of retinopathy and nephropathy and the severity of the depression (Table 3).

DISCUSSION
Chronic diseases generally lead to anxiety and depression due to the fear of the future, of organ loss and of death.The symptoms of the chronic and progressive disease Type 2 DM frequently yield depression because of emerging organ function loss and complications, disrupted quality of life and secondary biological changes to brain disease. 10The frequency of life-long depression in diabetic cases has raised two fold in comparison with the healthy control group. 8Moreover, depression is associated with behavior such as the habit of smoking, and weight gain rooting from lack of physical activity and inappropriate food intake, hence, may cause obesity and impaired glucose tolerance followed by organ defects. 8,11 is well known that the frequency of depression increases in cases with diabetes-related complications. 12In our study, the severity of depression symptoms and that of neuropathy were rising proportionally whereas no evidence was found to the significant correlation between depression severity and the presence of retinopathy and nephropathy.4][15][16] However, the number of studies investigating the relationship between depression symptoms and neuropathy is limited.Even though several systems were used in the assessment of depression severity until today, the UKNS was reported to be a realistic, objective and accurate scoring system for the assessment of diabetic peripheral neuropathy. 17Therefore, the use of UKNS in our study seems like quite a valid assessment method, and accordingly, there is a significant relationship between the UKNS.This finding supports the previous study results obtained by other scoring systems used for the determination of neuropathy severity and pointing out proportional increase in depression severity linked to neuropathy severity. 18,19We were not able to detect evident relationship between depression severity and TG.1][22] Heckbert et al. did not able to find any correlation between depression and LDL-C; whereas, Gary et al. neither found any correlation between depression and LDL-C however defined significant relationship between depression and TG. 23,24In another study, TG was found to be higher in patients with associated cardiac disease among Type 2 cases with major depression. 25As we did not perform sub group analyses in terms of cardiac diseases on our study patients, it does not seem possible to comment on such a correlation.On the other hand, one study showed that increase in TG levels leads to neuropathy independent of age, duration of disease and glycemic control. 26In the light of the current data, even if TG levels were not found to be so high, this increase may augment the severity of diabetic neuropathy, and this may be clinically vital for the approach towards neuropathy.
Though the impact of dyslipidemia on the severity of neuropathy has been evaluated in various studies, the mechanism of action of dyslipidemiadependent neuropathy is not yet clarified.As is well known, oxidative stress increases with Type 2 DM, and this leads to oxidation of various vital molecules containing lipids. 27It is advocated that the severity of diabetic neuropathy is related to these oxidized lipids. 28 conclusion, severity of depression increases along with that of neuropathy in diabetic patients.There is a relationship between TG levels and depression in diabetic patients.Due to these facts, the presence of neuropathy and depression might be investigated in diabetic patients especially with other micro vascular complications.The presentation of appropriate approach towards these associated conditions may have a positive effect on the patients' quality of life.It is also possible that treatment of hyperlipidemia cause decrease in the severity of neuropathy and hence contribute to the treatment of depression.

Figure 1 .
Figure 1.A correlation between the Beck depression severity and the level of triglyceride.

Figure 2 .
Figure 2. A correlation between the Beck depression severity and the UKNS.

Table 1 .
A comparison of clinical data between groups (*p<0.001 between all groups).

Table 2 .
A comparison of biochemical data between groups* (*p>0.05for all data).

Table 3 .
A correlation between the Beck depression severity and clinical and biochemical data