|Year : 2013 | Volume
| Issue : 2 | Page : 18-22
Albuminuria as a biomarker for risk of retinopathy in type II diabetic patients in Suez Canal area
Walid Abdelghaffar1, Waleed Ghobashy2, Mohammed Abdo3, Amani El-Baz3, Magda Ibrahim3
1 Department of Ophthalmology, Benha University, Banha, Egypt
2 Department of Ophthalmology, Suez Canal University, Ismailia, Egypt
3 Department of Physiology,Suez Canal University, Ismailia, Egypt
|Date of Web Publication||24-Jun-2014|
40 Nehro Street, Heliopolis, Cairo 11341
Source of Support: None, Conflict of Interest: None
Aim: The aim of this study is to estimate the prevalence of albuminuria in type II diabetes mellitus and report its influence, as a risk factor, for the presence and severity of diabetic retinopathy (DR). Subjects and Methods: During the period of January 2012 to May 2013, 420 type II diabetic patients were examined. Albuminuria adjusted for creatinine concentration was measured. Body mass index and hemoglobin A1c were also measured. Patients were evaluated by direct and indirect ophthalmoscopy and were classified as non-retinopathy, non-proliferative, proliferative or diabetic maculopathy. Results: The prevalence of albuminuria among type II diabetic patients in this study was 40.2%. The prevalence of microalbuminuria and macroalbuminuria were 30.7% and 9.5% respectively. The study also showed an association between the degree of albuminuria and severity of retinopathy. Nearly 97.5% of the macroalbuminuric patients had sight threatening forms of retinopathy (proliferative diabetic retinopathy + diabetic maculopathy DM) compared with 87%of the microalbuminuric and only 15% of the normoalbuninuric patients. Conclusion: Micro- or macroalbuminuria are highly prevalent in subjects with type II diabetes. Subjects with micro- and macroalbuminuria are more likely to have DR compared with those without albuminuria.
Keywords: Albuminuria, diabetic retinopathy, risk factors
|How to cite this article:|
Abdelghaffar W, Ghobashy W, Abdo M, El-Baz A, Ibrahim M. Albuminuria as a biomarker for risk of retinopathy in type II diabetic patients in Suez Canal area. Egypt Retina J 2013;1:18-22
|How to cite this URL:|
Abdelghaffar W, Ghobashy W, Abdo M, El-Baz A, Ibrahim M. Albuminuria as a biomarker for risk of retinopathy in type II diabetic patients in Suez Canal area. Egypt Retina J [serial online] 2013 [cited 2020 Apr 7];1:18-22. Available from: http://www.egyptretinaj.com/text.asp?2013/1/2/18/135243
| Introduction|| |
The World Health Organization (WHO) has reported that diabetes mellitus (DM) is a chronic disease and its complications impose economic consequences on individuals, families, health systems and countries. The prevalence of diabetes in all age groups world-wide was estimated to be 2.8% in 2000 (171 million people) and projected to be 4.4% in 2030 (366 million people).  Diabetic retinopathy (DR) is one of the leading causes of blindness in the world that increases the chance of losing the sight about 25 times higher compared with normal individuals. The more advanced the DR, the greater risk of visual loss. Furthermore, patients with DR are at higher risk for coronary heart disease, stroke, diabetic nephropathy, limb amputations and death.  The main risk factors for the development or progression of DR are duration of diabetes mellitus,  poor glycemic control , and hypertension. ,
The prevalence of microalbuminuria among diabetic patients is 15-20%. Persistence of microalbuminuria in diabetic patients is a risk marker not only for kidney and cardiac disorders but also for severe ocular morbidity. ,
The concordance of microalbuminuria and DR has been well reported in patients with type I diabetes; ,, however, for type II diabetes, there is a paucity of data especially from population-based studies regarding the association of microalbuminuria with DR. ,, The sensitive marker for the detection of diabetic nephropathy is to estimate excretion of microalbumin in urine; and for the detection of DR, to have a fundus evaluation after pupillary dilatation. ,
The present study was carried out to estimate the prevalence of albuminuria (micro- and macro-) in type II diabetes mellitus and report its influence as a risk factor for the presence and severity of DR.
| Subjects and Methods|| |
This cross-sectional study was carried out on patients with type II diabetes who were referred to the out-patient clinic in Suez Canal University Hospital between January 2012 and May 2013.
The diagnosis of diabetes mellitus was performed according to WHO criteria, reported by the WHO study group (1985).
Subsequent to completing preliminary questionnaires that covered personal data, the patients' ophthalmologic examination and laboratory tests were also carried out. All patients agreed to participate after signing an informed consent form, in accordance with the Helsinki Declaration of Human Rights. The procedures have been approved by the local Ethics committee. The subjects with pregnancy, proteinuria, serum creatinine more than 1.5 mg/dl and the causes of transient elevations in urinary albumin excretion (UAE), (i.e. urinary tract infection, hematuria, marked hypertension, acute febrile illness and heart failure) were excluded. Demographic data of the included patients are shown in [Table 1].
The "gold standard" to assess albuminuria is 24-h UAE. Because 24-h urine collection is cumbersome, American Society of nephrology guidelines suggest measuring albuminuria in a first morning void, either as urinary albumin concentration or adjusted for creatinine concentration, the albumin: creatinine ratio (ACR). , The ACR is done to compare the amount of albumin that is passing into the urine from the kidneys compared with the amount of creatinine present. Although one can always check for albumin levels in the urine by doing a simple test, the advantage of calculating the ACR is that this ratio remains unaffected by any kind of variation in the concentration in urine. Clinitek 100 (made by Bayer Corporation-Elkhart, IN 46515, USA) was used to measure microalbuminuria. Three urine samples were taken during 3-6 months and if two samples were positive, microalbuminuria was affirmed (the device shows the ratio of albumin to creatinine in mg/g). If the ratio was less than 30, the patient was normoalbuminuric. Ratios between 30 and 300 mg/g were indicative of microalbuminuria and above 300 mg/g revealed macroalbuminuria.
Ophthalmologic examination including visual acuity (by means of snellen charts), intraocular pressure (using applanation tonometry). Fundus examination was performed in all patients using direct and indirect ophthalmoscopy through dilated pupils. If required, fluorescein angiography was ordered. Patients were categorized according to the degree of their retinopathy. Retinopathy was classified as no retinopathy (NR), non-proliferative (including absent signs of DR or signs of non-proliferative DR, i.e. microaneurysms, hemorrhage, hard exudates), maculopathy, or proliferative (newly formed blood vessels and/or growth of fibrous tissue into the vitreous cavity). Patients with panretinal photocoagulation were classified as presenting proliferative DR. The severity of DR was graded based on the worst eye. In four patients in whom the presence of media opacities due to vitreous hemorrhage (two patients) and cataract (two patients) prevented fundoscopy in one eye, the contralateral eye was used to classify DR. No patient was excluded as a result of unreadable fundoscopy in both eyes. The diagnosis of proliferative DR based on fundoscopy performed by the ophthalmologists was used to classify the patients.
5 min after resting in the sitting position, the patients' blood pressure (BP) was measured by mercury sphygmomanometer. BP ≥140/90 mmHg was considered abnormal. Patient's medications including hypertensive drugs were also recorded. Body mass index (BMI) was also documented. Hemoglobin A1c (HbA1c) was ordered.
The patients' demographic data and baseline characteristics were presented using means, standard deviation and percentage. Chi-square test was employed to test the association between microalbuminuria and DR in type II diabetes. The magnitude of the difference in proportion of DR between type II diabetes with micro- and normoalbuminuria was presented along with 95% confidence interval.
| Results|| |
The study included 420 patients (226 male and 194 females). Methods of treatment ranged between dietary habits alone for 26 patients, oral agents for 321 patients, insulin for 54 patients and insulin plus oral agents for 19 patients. The age average was 54.3 ± 9.5 and the patients' duration of diabetes was between 1 and 39 years (mean = 20 ± 9.3). Duration of diabetes was less than 5 years in 25% of the patients, between 6 and 10 years in 22% and more than 10 years in 53% of them. Duration of diabetes was a strong predictor of severity of retinopathy (P = 0.001) [Table 2]. 53.09% of the patients had NR, 23.09% had non-proliferative diabetic retinopathy, 15.71% diabetic maculopathy DM, 8.09% proliferative diabetic retinopathy (PDR). About 175 of patients had BP ≥140/90 mmHg, 146 of whom were under treatment with antihypertensive drugs. There was no significant relationship (P = 0.27) between high BP and different degrees of retinopathy. Gender also had no significant correlation with severity of retinopathy (P = 0.21).
The relationship between different types of retinopathy and risk factors such as HbA1c, FBS, BMI and age were found to be significant [Table 3].
Examination of urine samples in 251 subjects (60%) showed normal range of albumin excretion (normoalbuminuria). About 30.7% of the patients were microalbuminuric and 9.3% had macroalbuminuria. [Table 4] shows the significant relationship between different grades of retinopathy and albuminuria (P = 0.025).
|Table 2: Relationship between duration of diabetes and different types of retinopathy|
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|Table 4: Relationship between different types of retinopathy and albuminuria|
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| Discussion|| |
Diabetes mellitus is one of the most common metabolic diseases in which either the hormone insulin is lacking or the body's cells are insensitive to insulin effects. Microvascular complications of diabetes mellitus, especially retinopathy and nephropathy are the leading cause of blindness and end stage renal disease respectively in many populations both developed and developing countries. ,
Albumin is the most abundant plasma protein, with a molecular weight of approximately 69,000 D and is mainly responsible for total plasma colloid osmotic pressure. The repeated presence of albuminuria in diabetics' urine samples reveal damage to the glomerular basement membrane and should be considered an early diabetic nephropathy.  The present study primarily reports the prevalence of albuminuria (micro- and macro-) among persons with type II diabetes and evaluates its role as a risk factor for presence and severity of DR.
The prevalence of albuminuria among type II diabetic patients in this study was 40.2%. Many of the studies showed a prevalence between 16% and 53% respectively. ,,,, The variation in rates could be a result of the different methods used in those studies, the population and or the ethnic group involved, or variations in controlling blood sugar levels.
The prevalence of microalbuminuria and macroalbuminuria in our study was 30.7% and 9.5% respectively. Parving et al., in their study have reported a prevalence rate of 22% for microalbuminuria in diabetes type II,  whereas Lunetta et al. reported a prevalence rate of 15%.  The above-mentioned studies show that there is a significant relationship between the degree of retinopathy and albuminuria.
However, there are few studies contradicting such a relationship. Erasmus et al., showed that in 113 patients suffering from non-insulin dependent diabetes mellitus, the prevalence rate of microalbuminuria was as high as 54% among males and 59% among females. Prevalence of retinopathy and hypertension was 16% and 41% respectively. They concluded that microalbuminuria may not predict retinopathy and occurs independently of both glycemic control or elevated BP level.  The population chosen for the study influences the different incidences achieved in various studies.
This study showed that in addition to disease duration, age of patients, HbA1c, BMI-albuminuria is a contributing factor to the degree of retinopathy (P = 0.001) and this association can be explained by the common mechanisms involved in tissue damage by all those factors. Only 37% of normoalbuminuric patients had some degree of retinopathy, whereas 81% of the microalbuminuric and all the macroalbuminuric patients had retinopathy.
The study also showed an association between the degree of albuminuria and severity of retinopathy. About 97.5% of the macroalbuminuric patients had sight threatening forms of retinopathy (PDR + DM) compared with 87% of the microalbuminuric and only 15% of the normoalbuninuric patients. The Diabetes Control and Complications Trial study in type I diabetes mellitus reported that there is a relationship between DR and diabetic nephropathy.  Within the study group that showed evidence of minimal DR at baseline, 10% had elevated urinary albumin excretion rates. For the population with type II diabetes, though the association between advanced degrees of DR and macroalbuminuria (or proteinuria) is well-known, the relationship with lower levels of urinary albumin excretion within the range of microalbuminuria is controversial. Some investigators have reported a positive association, , whereas in other studies this has not been observed. , Boelter et al.,  also reported the presence of renal involvement, including UAE within the microalbuminuria range in type II diabetic patients with PDR. They emphasized that all patients with PDR should undergo an evaluation of renal function including urinary albumin measurements.
The microvascular damage in type II diabetic patients goes hand in hand in retinal and renal vessels, thus excretion of albumin in urine can be regarded as a sign of kidney involvement and can reflect retinal vessels damage. Further prospective studies should be carried out to evaluate the effect of lowering albumin excretion on the reduction of blood vessel damage and further well-designed cohort studies for expressing the relation of microalbuminuria and retinopathy should be performed before type II diabetic patients develop microvascular complication.
| Conclusion|| |
Micro- or macroalbuminuria are highly prevalent in patients with type II diabetes. Patients with micro- and macroalbuminuria are more likely to have DR compared with those without albuminuria. If longitudinal studies confirm these findings, diabetic patients who have microalbuminuria may benefit from close ophthalmologic follow-up.
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[Table 1], [Table 2], [Table 3], [Table 4]