Abstract
Aims: To assess the influence of microalbuminuria and hyperlipidemia on the occurrence and severity of diabetic retinopathy.
Materials and methods: This prospective cross-sectional study carried out over a period of 2 years, type 1 and 2 diabetic patients seeking ocular evaluation for diabetic retinopathy (DR) were assessed for presence and severity of DR. Retinal findings were correlated to severity of microalbuminuria and hyperlipidemia.
Results: 246 patients were included in the study. DR of any grade seen in 44% patients, 24% in type I DM and 96% in type II DM. Microalbuminuria (P < 0.01) and dyslipidemia (P < 0.05) were found to be highly significant risk factors for the development and increasing severity of DR.
Conclusion: Microalbuminuria and hyperlipidemia are strong predictor of DR. Although not directly involved in the pathogenesis, microalbuminuria can help identifying patients at risk for developing more severe diabetic eye disease. Microalbuminuria and hyperlipidemia warrants intensive monitoring of both retinal and renal status.
Introduction
Diabetic retinopathy is one of the leading cause of blindness in the world.1 Duration of diabetes is probably the strongest predictor for the development and progression of retinopathy.2,3,4
Microvascular complication in DM leads to diabetic retinopathy and diabetic nephropathy1. Retinopathy and nephropathy are both related to endothelial dysfunction mediated microvascular complication of DM especially in type 1 and to lesser extent in type 2.5 Mogensen (1987) – microalbuminuria a predictor of clinical diabetes. Cruiskshanks et al. (1993) showed association between microalbuminuria and diabetic retinopathy.6 Witra et al. (1999) retinopathy is independently related to microalbuminuria in type 2 DM.7 Other studies also established the relationship between diabetic retinopathy and microalbuminuria.8,9,10,11
Diabetic retinopathy is a common complication of DM characterized by macular edema and frequently accompanied by lipid exudation.12 Krock Collaborative Group (1984) found elevated serum lipid level increase the risk for development of hard exudates at the same time. Dorman et al.13 at the same time found higher cholesterol level in patient with diabetic retinopathy. While Kostrade JN (1991)14 found decrease in serum lipid level associated with decrease in development of hard exudates. Aikermann et al. (1992)15, Klein et al. (1998)16 suggested elevated level of serum cholesterol associated with increase severity of hard exudates.
Chen et al. (2003)17 surprisingly suggest that dyslipidemia but not hyperglycemia induces inflammatory adhesion molecules in human retinal vascular endothelial cells which are suppose to play a very important role in development of early diabetic retinopathy.
Keeping in mind the increasing number of cases and the potential hazards to the vision and renal function in diabetic patients, present cross-sectional study tried to evaluate degree of association between severity of diabetic retinopathy with microalbuminuria and hyperlipidemia in context of India particularly in southern Rajasthan.
MATERIAL AND METHODS
This prospective cross-sectional study was carried out in Department of Ophthalmology and Department of Endocrinology, RNT Medical College & associated MBGH, Udaipur over a period of 2 years.
Inclusion Criteria:
1.All patients with type I and type II diabetes, which is defined as fasting glucose more or equal to 120 mg/dl or a 2 hr post glucose load, plasma glucose of more than or equal to 200 mg/dl or random plasma glucose of than or equal to 200 mg/dl.
2. Patients who gave voluntary informed consent.
3. Mentally and physically fit patient up to a minimum level of participation in the study.
Exclusion Criteria:
1.Pregnancy
2.Chronic alcoholics
3.Malignant hypertension
4.Chronic blood loss
5.Primary renal disorder
6.Glaucomatous patient
7.Active systemic infection
8.Co-existing ocular disorders like uveitis, opaque/hazy media, high myopia, vitreoretinal degeneration and dystrophy, retinitis, pigmentosa and ocular surgeries < 6 month duration.
Detailed ocular examination was carried out by using Snellen’s chart for BCVA, S/L biomicroscopy by 90D for fundus examination, tonometry by Schiotz tonometer for IOP assessment. Ophthalmoscopic examination done under full mydiosis (direct/indirect) and FFA if required. Patient having diabetic retinopathy were classified according to ETDRS classification.18
Clinically significant macular edema was diagnosed based on the modified ETDRS protocol.19
(i) Retinal thickening at or within 500 µm of centre of macula.
(ii) Hard exudates at or within 500 µm of centre of macula if associated with adjacent retinal thickening.
(iii) Zone or zones of retinal thickening one disc area in size, at least part of which was within one disc diameter of centre of macula.
Microalbuminuria was measured in spot urine sample by using S8 specific dipsticks (Clinitek) which can detect albumin in urine at concentration as low as 3-4 mg/dl. Change in colour of stick can be used to determine albumin excretion in 24 hrs by comparison with standardized colour index. Besides albumin these sticks can also detect concentration of creatinine in urine so the albumin / creatinine ratio can also be determined.
Other lab test include fasting and 2 hrs postprandial blood sugar, glycosylated Hb (HbA1c) and lipid profile. Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/day.20 While > 300 mg/day albumin in urine defined as overt nephropathy. Dyslipidemia was defined using NCEP ATP III guidelines as: Total cholesterol ≥ 200 mg/dl and or HDL cholesterol < 40 mg/dl or LDL cholesterol21 > 100 mg/dl and/or triglycerides > 150 mg/dl and HbA1c > 7% was considered abnormal.20
Statistical analysis
Yules’ coefficient of association has applied to determine the nature and degree or extent of association between two attributes. On applying Yules’ coefficient value of coefficient ‘Q’ lies between ±1.
Q = +1 is a perfect positive association.
Q = -1 perfect negative association
Q = 0 two attributes are independent
On applying Yules’ coefficient in given data retinopathy has found positive association with all the three variables i.e., macroalbuminuria, haemoglobin and abnormal lipids. Out of these three variables Yules’ coefficient ‘Q’ shows very little association with abnormal profile.
Positive association with uncontrolled glycosylated haemoglobin and high degree of positive association with macroalbuminuria.
Table 1.
Variable
|
Retinopathy
|
No retinopathy
|
P value
|
No.
|
%
|
No.
|
%
|
Albuminuria:
No albuminuria
Microalbuminuria
Macroalbuminuria
|
19
69
22
|
20%
53%
88%
|
70
63
3
|
 80%
47%
12%
|
P<0.01
Q (0.740)
|
Lipid profile:
Normal
Abnormal
|
53
57
|
37%
54%
|
80
48
|
63%
46%
|
 P=0.05
Q (0.27)
+ve association
|
Glycosylated haemoglobin
Well controlled (<7%)
Uncontrolled (>7%)
|
44
66
|
34%
56%
|
84
52
|
36%
44%
|
P=0.042
Q (0.416)
|
RESULTS:
In this cross-sectional study, 246 type I and type II diabetic patients for evaluation of their diabetic retinopathy status during the study period were included. The age of patients ranged from 15-60 years. The study included 158 males and 88 females.
Duration of diabetes included recently diagnosed to 30 years. Occurrence of risk factors like microalbuminuria, systemic dyslipidemia, metabolic control (HbA1c) is enumerated in Table 2.
Table 2: Demographic and other systemic parameter of the study patients
Risk factors
|
Range
|
Age
|
15-60 years
|
Duration
|
Recently diagnosed to 30 years
|
Gender:
Male
Female
|
155
88
|
Lipid profile:
Normal
Abnormal
|
141
105
|
Albuminuria :
Microalbuminuria
Macroalbuminuria (Overt)
|
132
25
|
Metabolic control (HbA1c):
Well control (<7%)
Uncontrol (> 7%)
|
128
66
|
Out of 246 patients, 110 patients (44%) showed evidence of diabetic retinopathy, out of these 95 patients having NDPR and 15 patients (13%) had PDR.
Out of NDPR, 57 patients (47%) mild, 19 (17%) moderate, 11 (10%) severe, 7 patients (6%) very severe diabetic retinopathy. 6 patients (5%) had CSME
Out of 110 patients, 65 (59%) were having macular involvement.
Out of 246 patients, 105 patients (41%) had abnormal lipid profile. Out of 105 patients, 57 (54%) were having diabetic retinopathy.
Out of 57 patients, 46 patients (80%) had hypercholesterolemia with or without raised triglycerides level.
Eleven patients were having PDR and all of those associated with increase level and all patients with CSME (6 patients) were showing hypercholesterolemia.
Table 3
Prevalence of diabetic retinopathy in patients having both microalbuminuria and dyslipidemia
|
Retinopathy
|
No retinopathy
|
Total
|
Only microalbuminuria
|
69 (52.2%)
|
63
|
132
|
Only abnormal lipid profile
|
57 (54.4%)
|
48
|
105
|
Both microalbuminuria and abnormal lipid profile
|
38 (63.4%)
|
22
|
60
|
Out of 110 patients having diabetic retinopathy, 38 patients were having both abnormal lipid profile and microalbuminuria in comparison to 22 (16%) patients out of 136 with diabetic retinopathy.
Conclusion:
Present study suggests that diabetic patients with microalbuminuria have significantly higher chances for the concomitant presence of diabetic retinopathy (diabetic retinopathy) in comparison to patients with non-microalbuminuria (52% v/s 20%). Frequency and severity of diabetic retinopathy were also found to be increased with increased amount of albumin in urine.
An independent association between microalbuminuria and non-proliferative diabetic retinopathy (NPDR) was observed in a study from Cameroon by Sonbngwi et al.22. More recent study done by Ahmed et al. (2000)23 showed higher incidence of proliferative diabetic retinopathy in microalbuminuria, positive patients. The stages of retinopathy was compared with mean microalbuminuria level, which was found to be lowest in background diabetic retinopathy and highest (macroalbuminuria level) in proliferative diabetic retinopathy.
These findings support that both diabetic retinopathy and nephropathy occurs in parallel way, both are microangiopathic complications of diabetes and probably diabetic nephropathy per se increase the risk of development of diabetic retinopathy by elevating blood pressure and serum level of fibrinogen.24,25 These findings stress on the need for close monitoring for diabetic retinopathy in patients with microalbuminuria to prevent irreversible visual loss. These association also indicates the overall more grave prognosis in patients with diabetic retinopathy, which call for close monitoring of renal and cardiovascular function in the presence of diabetic retinopathy.
The study also established a correlation between diabetic retinopathy and hyperlipidemia because elevated lipids are involved in atherosclerosis and vessel wall stenosis. Furthermore recent concept of role of high serum level of apolipoprotein level in the pathogenesis of capillary occlusion and severe retinopathy demands the need of intensive investigatory approach in this issue.
The limitations of this study include: (1) small sample size, (2) the setting of study at tertiary care centre.
Larger prospective longitudinal population-based studies are required to categorically ascertain this association of microalbuminuria and hyperlipidemia with type 1 and type 2 DM.
In conclusion, we have observed a significant correlation between albuminuria and prevalence of diabetic retinopathy. Hence detection of microalbuminuria may serve as a non-invasive sensitive indicator for the early detection of diabetic retinopathy.
This, in turn, may reduce the irreversible visual loss due to diabetic retinopathy.
Our study also demonstrated relationship between hyperlipidemia and severity of diabetic retinopathy. Hard exudates were commonly associated with hypercholesterolemia and proliferative diabetic retinopathy (PDR) was more frequently associated with hypertriglyceridemia.
Hence presence of microalbuminuria and dyslipidemia in diabetic patient should alert the physician for the potential presence of sight threatening complication of diabetic retinopathy.
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