CORRELATION BETWEEN EYE AND RENAL COMPLICATIONS OF DIABETES/KORELACIJA OCNIH I BUBREZNIH KOMPLIKACIJA SECERNE BOLESTI.
Diabetes mellitus is one of the most common metabolic diseases with an increasing incidence, and its complications can affect almost all tissues and organs, causing high morbidity, disability and mortality . Diabetic retinopathy is an eye complication of diabetes and it is the main cause of visual function loss in the working-age population . Blindness is 25 times more common in diabetics than in the general population . The consistent risk factors for diabetic retinopathy include duration of diabetes, age of the patient, nephropathy/albuminuria, genetic factors, pregnancy and degree of retinopathy, and variable risk factors including hyperglycemia/glycosylated hemoglobin (HbA1c), hypertension, dyslipidemia, physical inactivity and obesity . Two major processes are involved in the development of diabetic retinopathy and clinically significant macular edema: occlusion of the retinal capillaries and other blood vessels, resulting in ischemia, and abnormal vascular permeability . Another significant chronic complication of diabetes is diabetic nephropathy and it is one of the leading causes of terminal renal failure, as well as mortality at this stage of the disease . Kidney damage rarely occurs in the first 10 years of diabetes, usually taking 15--25 years to develop . It is important to inform and educate people with diabetes about the illness, risk factors and complications that accompany it, in order to actively participate in the screening process, to regularly monitor their vision and renal function, and to get treated in a timely manner.
The aim of this study was to examine eye and kidney disorders of patients with diabetes, and assess the correlation between them.
Material and Methods
A retrospective study included 45 patients with diabetes mellitus who underwent a routine ophthalmological examination at the Eye Clinic of the Clinical Center of Vojvodina in Novi Sad. The study was approved by the Ethics Committee of the Clinical Center of Vojvodina, Novi Sad, Serbia. Patients were divided into three groups (according to the International Clinical Diabetic Retinopathy Disease Severity Scale) : patients without diabetic retinopathy (WDR), patients with non-proliferative diabetic retinopathy (NPDR), and patients with proliferative diabetic retinopathy (PDR). Each group included 15 patients who suffered from type 2 diabetes mellitus for more than ten years.
Graph 1. Mean HbA1c levels (%) in blood in groups: WDR, NPDR, PDR Grafikon 1. Proseena koncentracija HbA1c (%) u krvi u odnosu na grupe: WDR, NPDR, PDR Legend: WDR - without diabetic retinopathy; NPDR - non-proliferative diabetic retinopathy; PDR - proliferative diabetic retinopathy; HbA1c - glycosylated hemoglobin Legenda: WDR - bez dijabetesne retinopatije; NPDR - neproliferativna dijabetesna retinopatija; PDR - proliferativna dijabetesna retinopatija; HbA1c - glikozilirani hemoglobin WDR 7,95 NPDR 8,15 PDR 8,48 Note: Table made from bar graph. Graph 2. Percentage (%) of patients without and with maculopathy Grafikon 2. Procenat (%) pacijenata bez i sa makulopatijom PDR NPDR Without maculopathy 40 With maculopathy 40 20 Note: Table made from bar graph.
The following data were recorded: patient's name and surname; gender; fasting blood glucose (FBG) and HbA1c from venous blood (according to Guidelines for Diabetes Mellitus  it should not exceed 7 mmol/l for FBG and 6.5% for HbA1c); level of diabetic retinopathy and presence or absence of maculopathy (based on fundus biomicroscopy with the slit lamp in artificial mydriasis, fluorescein angiography and optical coherence tomography); best corrected visual acuity (BCVA) using the Snellen optotype (in decimal values); intraocular pressure (IOP) measured by applanation tonometry; urea and creatinine in the serum (reference values for serum urea 2--7 mmol/l, and serum creatinine 45--90 [micro]mol/l in women, and 60--110 [micro]mol/l in men); creatinine clearance (reference values 97--137 ml/min in men, and 88--128 ml/min in women) and screening of 24-hour albuminuria after 24-hour urine collection.
Statistica 12.0 software was used for statistical data analysis. Statistical significance of the difference between the arithmetic means of three samples, with one variable of variance, was calculated using the analysis of variance (ANOVA). The F0 test of freedom, variance between groups divided by variance within groups, was compared with Snedecor's F-distribution, which is the probability test. If F0 < F, there was no statistically significant difference (p > 0.05), whereas if F0 > F, there was a statistically significant difference (p < 0.05) with a risk error of 5%.
Graph 3. Mean values of the best corrected visual acuity (BCVA) for the right eye, left eye and average for both eyes in groups: WDR, NPDR, PDR Grafikon 3. Srednje vrednosti najbolje korigovane vidne ostrine (BCVA) za desno, levo i prosek za oba oka u grupama: WDR, NPDR, PDR Legend: WDR - without diabetic retinopathy; NPDR - non-proliferative diabetic retinopathy; PDR - proliferative diabetic retinopathy; HbA1c - glycosylated hemoglobin Legenda: WDR - bez dijabetesne retinopatije; NPDR - neproliferativna dijabetesna retinopatija; PDR - proliferativna dijabetesna retinopatija; HbA1c - glikozilirani hemoglobin WDR NPDR PDR BCVA Odex 0,81 0,86 0,39 BCVA Osin 0,85 0,82 0,51 BCVA average for both eyes 0,83 0,84 0,45 Note: Table made from bar graph.
This study included a total of 45 patients, of which 17 (37.78%) were female and 28 (62.22%) male.
The average FBG levels in all three groups of patients exceeded the reference ranges. The highest levels were recorded in patients with PDR (11.27 mmol/l), followed by patients with NPDR (10.63 mmol/l) and finally in patients with WDR (9.37 mmol/l). There was no statistically significant difference between the groups in regard to FBG (F0 = 1.02, F = 3.22, F0 < F, p > 0.05).
The highest mean HbA1c level was observed in patients with PDR--8.48%, while it was 8.15% in the group of patients with NPDR, and 7.95% in patients with WDR (Graph 1). There was no statistically significant difference between the observed groups (F0 = 1.69, F = 19.5, F0 < F, p > 0.05).
Of the 30 patients with diabetes-induced eye diseases, diabetic maculopathy was found in 18 patients (60%). Of those, 6 patients (20%) were in the NPDR group and 12 of them (40%) in the PDR group (Graph 2).
Visual acuity (VA) was measured by Snellen optotype, and the results were expressed in decimals. The mean values of BCVA in both eyes were significantly lower in the PDR group (mean value of 0.45) in comparison with the values in patients with NPDR (mean value of 0.84) and WDR group (mean value of 0.83) (Graph 3). There was a statistically significant difference in mean BCVA values in both eyes (F0 = 9.99, F = 3.19, F0 > F, p < 0.05) in the observed groups.
Mean values of IOP, measured by applanation tonometer, were not elevated in any patient, i. e. in all patients values ranged from 10 to 21 mmHg.
Mean serum urea was 6.61 mmol/l in the WDR group, in the NPDR group it was 6.16 mmol/l, and the highest value was 7.37 mmol/l, in the PDR group. There was no statistically significant difference in mean values of urea between these three groups (F0 = 1.41, F = 19.5, F0 < F, p > 0.05).
Mean serum creatinine levels were highest in the PDR group (106.13 [micro]mol/l), followed by the NPDR group (94 [micro]mol/l) and lowest among the patients in the WDR group (90.73 [micro]mol/l). There was no statistically significant difference in creatinine levels between these groups (F0 = 1.05, F = 19.5, F0 < F, p > 0.05).
The lowest mean creatinine clearance was found in the PDR group--72.80 ml/min. In the NPDR group, it was 101.47 ml/min, and in the WDR group it was 95.33 ml/min (Graph 4). There was a statistically significant difference in mean levels of creatinine clearance in the studied groups (F0 = 3.36, F = 3.22, F0 > F, p < 0.05).
The mean albuminuria level was highest in patients with PDR--346.31 mg/24h, followed by NPDR patients --71.80 mg/24h, while the lowest level was observed in patients in the WDR group--12.45 mg/24h (Graph 5). There was a statistically significant difference in mean albuminuria level in the studied groups (F0 = 43.67, F = 3.22, F0 > F, p < 0.05).
Complications of diabetes are directly related to disease control . Mean values of FBG and HbA1c were highest in the PDR group (11.27 mmol/l and 8.48%, respectively), which corresponds to the fact that severe forms of diabetic retinopathy are found in patients with poor metabolic regulation [9, 10]. The mean values of HbA1c in the FinnDiane study were similar to values found in our patients and amounted to 8.6% in patients with PDR . It has been proven that glycemic control, especially when initiated in the early stage of the disease, can prevent or delay development of diabetic retinopathy . It has been established that 1% reduction of HbA1c reduces the risk of retinopathy by 40% and mortality due to diabetic complications by 25% [8, 12].
Macular edema that occurs in both forms of diabetic retinopathy is the most common cause of visual impairment. The Wisconsin Epidemiological Study of Diabetic Retinopathy found that in patients with moderately severe and severe NPDR, macular edema occurred in 38% of cases, while in patients with proliferative form it occurred in 71% of cases . In our study, of 30 patients with diabetes-induced diseases, diabetic maculopathy was found in 60% of patients. Of these, 20% of patients were in the NPDR group and 40% in the PDR group. A statistically significant difference in the mean values of the BCVA in both eyes was established between the groups; values were significantly lower in the PDR group, which is in accordance with the study from India, where the BCVA was proportionally reduced with the severity of diabetic retinopathy .
Diabetic nephropathy is a very significant chronic complication of diabetes and is one of the leading causes of terminal renal failure and mortality in this stage of the disease . In our research, PDR patients had a mean serum urea levels above reference ranges, amounting to 7,37 mmol/l. These levels were significantly higher in the study carried out in India--16,17 mmol/l . In our study, the mean serum creatinine levels were 94 [micro]mol/l in the NPDR group and 106.13 [micro]mol/l in the PDR group. These results are very similar to the Indian study which reported the mean value of 95,92 [micro]mol/l in the NPDR group and 112,64 [micro]mol/l in the PDR group . In this study there was a statistically significant difference in mean creatinine clearance level in the observed groups (WDR, NPDR and PDR). The lowest mean creatinine clearance was observed in the PDR group--72,80 ml/min. In the NPDR group, it amounted to 101,47 ml/min, and in the WDR group it was 95,33 ml/min. In the FinnDiane study, mean creatinine clearance in WDR, NPDR, and PDR groups was 93 ml/min, 79 ml/min and 59 ml/min, respectively; in the Chronic Renal Insufficiency Cohort study, values for the same groups were 42.8 ml/min, 36.6 ml/min and 32.2 ml/min, respectively, while the Indian study reported a mean creatinine clearance of 95.2 ml/min in patients with NPDR and 80.2 ml/min in patients with PDR [11, 14, 15]. Although the values are quite different among the studies, it can be seen that creatinine clearance was significantly lower in severe forms of retinopathy. Mean albuminuria levels in the WDR, NPDR and PDR groups were 12.45 mg/24h, 71.80 mg/24h and 346.31 mg/24h, respectively. There was a statistically significant difference among the groups, which points to the fact that in patients with advanced diabetic proliferative eye diseases there was proportional renal function impairment, manifesting in 24-h albuminuria. In FinnDiane study, these
values were significantly lower (8 mg/24h, 31 mg/24h and 135 mg/24h) . Our findings support the hypothesis that common mechanisms may cause both retinal and renal vascular changes and that there is a correlation between the degree of diabetic retinopathy, 24-h albuminuria and kidney function [11, 15-17].
1. Severe forms of diabetic retinopathy were found in patients with poor metabolic regulation, i. e. in patients with higher blood sugar levels and glycosylated hemoglobin.
2. Patients with proliferative diabetic retinopathy had a higher incidence of macular edema as well as significantly reduced best-corrected visual acuity in both eyes, while the values of intraocular pressure were within normal limits.
3. Serum urea and creatinine, as well as 24-h albuminuria, showed the highest levels in patients with proliferative diabetic retinopathy, whereas creatinine clearance was the lowest in this group.
4. It has been established that there is a correlation between diabetic eye and kidney diseases, and that the degree of eye damage was proportional to the degree of renal function damage; this opens up a possibility that there may be a link between the pathogenetic mechanisms causing diabetic retinopathy and nephropathy.
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Rad je primljen 21. VI 2018.
Recenziran 17. VII 2018.
Prihvacen za stampu 20. VIII 2018.
Health Center Novi Sad, Novi Sad (1)
University of Novi Sad, Faculty of Medicine, Novi Sad (2)
Clinical Center of Vojvodina, Eye Clinic, Novi Sad (3)
Katarina ANISIC (1,2) and Sofija DAVIDOVIC (2,3)
Corresponding Author: Dr Katarina Anisic, Dom zdravlja Novi Sad, 21000 Novi Sad, Bulevar Cara Lazara 75, E-mail: firstname.lastname@example.org, email@example.com
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|Title Annotation:||ORIGINAL STUDIES/ORIGINALNI NAUCNI RADOVI|
|Author:||Anisic, Katarina; Davidovic, Sofija|
|Date:||Sep 1, 2018|
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