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 Table of Contents  
Year : 2022  |  Volume : 34  |  Issue : 3  |  Page : 245-249

Diabetic nephropathy may predict the retinal changes of patients with diabetes: An Indian population-based study

1 Department of Ophthalmology, Northern Railway Central Hospital, New Delhi, India
2 Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Date of Submission27-Oct-2021
Date of Decision01-Dec-2021
Date of Acceptance13-Dec-2021
Date of Web Publication22-Dec-2022

Correspondence Address:
Dr. Sahil Agrawal
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/kjo.kjo_208_21

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Purpose: This study aimed to study and correlate fundus changes in patients with Type 2 diabetes mellitus with different stages of nephropathy. Materials and Methods: It is a prospective, observational study involving 100 patients at a tertiary health-care institute. Type 2 diabetic patients with diabetic nephropathy (DN) were enrolled. Those with uncontrolled hypertension, history of other ocular diseases, or surgeries were excluded. DN was defined as – microalbuminuria, macroproteinuria, and massive proteinuria based on 24-h urine protein analyser values. Participants underwent complete ophthalmic examination with fundus examination, fundus fluorescein angiography, and optical coherence tomography and were graded into various stages of diabetic retinopathy. The influence of nephropathy on retinal changes was assessed using Pearson's correlation analysis. Results: The study population included those with a median age of 56 years (range 38–79 years). In the group with microalbuminuria, 10 (62%) eyes did not have any retinopathy changes. In the macroproteinuria group, 61 (53%) showed mild-to-moderate nonproliferative diabetic retinopathy (PDR). In addition, 30 eyes of patients (48%) with massive proteinuria had PDR which were all statistically significant. Also in 32 eyes (16%) of DN patients, clinically significant macular edema was present, most of which, i.e., 24 (75%), were in the macroproteinuria group. Conclusions: These findings indicated that the severity of proteinuria was significantly associated with fundus changes in Type 2 diabetic patients. Thus, we conclude that DN is a marker of retinopathy and timely ophthalmic evaluation of patients should be done.

Keywords: Diabetes, diabetic nephropathy, diabetic retinopathy, fundus, glycated hemoglobin

How to cite this article:
Gupta S, Agrawal S, Chaudhary SK, Jhamb M. Diabetic nephropathy may predict the retinal changes of patients with diabetes: An Indian population-based study. Kerala J Ophthalmol 2022;34:245-9

How to cite this URL:
Gupta S, Agrawal S, Chaudhary SK, Jhamb M. Diabetic nephropathy may predict the retinal changes of patients with diabetes: An Indian population-based study. Kerala J Ophthalmol [serial online] 2022 [cited 2023 Feb 8];34:245-9. Available from: http://www.kjophthal.com/text.asp?2022/34/3/245/364719

  Introduction Top

Diabetes Mellitus (DM) is one of the leading causes of blindness worldwide. At present, India has about a million diabetics.[1] Rising prevalence requires proper study to assess diabetics and its related complications. There has been a multifold rise in cases of DM in the COVID-19 pandemic, especially with restriction of movement due to lockdowns, work from homes and decreased exercise including running, gym and use of steroids.[2],[3] Lack of exercise and improper diet caused by poor availability of healthy food along with psychological stress may lead to significant weight gain and thereby DM.[4]

Diabetes is a systemic disease and may lead to various micro and macrovascular complications such as diabetic retinopathy (DR), diabetic nephropathy (DN), and peripheral neuropathy. It is estimated that within 15–20 years of diagnosis, more than 75% of diabetic patients develop DR.[5] Approximately 40% of people with diabetes develop DN which has become the leading cause of end-stage renal disease in many countries.[6],[7],[8] Globally, the number of people with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and the number with vision-threatening diabetic retinopathy will increase from 37.3 to 56.3 million if prompt action is not taken.[9]

Although prevalence and risk factor for DR in Type 2 diabetes is extensively studied,[10],[11],[12] there are fewer data correlating DR and DN; with no major studies in the Indian population. Therefore, the current study strived to investigate relationship between changes of DR and its severity in patients with different stages of DN.

  Materials and Methods Top

It was a prospective observational study done at the department of ophthalmology of a tertiary health-care institute. The study protocol was reviewed and approved by the institute ethics committee. Written informed consent was obtained from all individual participants before the start of the study.

The study was conducted on a total of 100 patients (195 eyes). Patients with DN due to Type 2 diabetes were included in the study. Patients with cardiovascular disease, malignancy, pregnancy, and acute intercurrent illness who could otherwise have non-DN were excluded. In addition, patients with a previous history of laser photocoagulation, glaucomatous and myopic patients, and other retinal vascular and proliferative diseases were excluded.

Patients underwent blood profile tests including serum creatinine, urine albumin excretion, blood pressure, fasting blood glucose, glycated hemoglobin (HbA1C), and detailed ophthalmic examination. They were divided into three groups – microalbuminuria (urinary albumin excretion of 30–300 mg/day), macroproteinuria (urinary albumin excretion of ≥300 mg/day), and massive proteinuria (urinary albumin excretion of ≥3000 mg/day) based on 24-h urine protein values using urine protein analyzer. At the time of enrolment in the study, a complete medical and ocular history was taken along with a comprehensive ophthalmic examination. Their fundus examination was done using fundus photography, fundus fluorescein angiography, and optical coherence tomography. It was then graded into no DR, mild, moderate-to-severe non-PDR (NPDR) and PDR. Diabetic macular edema was categorized into clinically significant macular edema (CSME) and non-CSME.

Statistical analysis was performed on SPSS version 24 and STATA 12.1 (StataCorp, College Station, TX). Median values were used to present continuous variables, while categorical variables were expressed as numbers or percentage values. Comparisons between continuous data were performed using the Mann–Whitney U-test. A Chi-square (χ2) test was used to analyze the differences between categorical data. Statistical significance was established for results with a P < 0.05.

  Results Top

The study was done in 100 patients (195 eyes) with a median age of 56 years (range 38–79 years). Out of 100 patients, 63 were male and 37 were female. The duration of diabetes ranged from 1 to 35 years. Forty-seven patients had diabetes for more than 10 years. About 77% of patients had associated hypertension (HTN). In five of the total eyes, fundus could not be visualized due to the presence of advanced cataracts in 4 of them and total corneal opacity in one. Seventy-one patients were on insulin, and the rest 29 were on oral hypoglycemic drugs.

In our study, of the 195 eyes screened, 51 (26%) showed no signs of DR, 50 (25%) showed mild NPDR, 41 (21%) had moderate NPDR, 14 (7%) had severe NPDR, and 39 (20%) had PDR. Furthermore, based on 24-h urine protein analysis, the majority, i.e., 60% of patients, had proteinuria between 300 and 3000 mg/24 h and a significant proportion, i.e., 32%, had massive proteinuria. Only 8% of patients had microalbuminuria.

The majority, i.e., 10 (62.5%), eyes of patients with microalbuminuria had no changes of DR, four (24%) had mild-to-moderate NPDR, while the remaining two (12.5%) had PDR. Amongst those who had macroproteinuria, of them 41 eyes (35.3%) had no DR changes, 33 (28.4%) had mild NPDR, 28 (24.1%) had moderate NPDR, seven (6%) had severe NPDR, and the remaining seven (6%) had PDR changes. All patients with massive proteinuria had some form of DR, i.e., 15 (23.8%) had mild NPDR, 11 (17.4%) had moderate NPDR, seven (11.1%) had severe NPDR, while almost half of them, i.e., 47.6%, had PDR. The relationship between proteinuria and retinopathy was found to be statistically significant (P < 0.001) [Figure 1].
Figure 1: Graphical correlation between grades of nephropathy and grades of retinopathy

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In addition, out of sixteen patients with microalbuminuria, only 3 had maculopathy. Among patients with macroproteinuria, 24 had CSME, and four had non-CSME maculopathy. In massive proteinuria group, eight patients had maculopathy [Figure 2].
Figure 2: Graphical correlation between grades of nephropathy and grades of maculopathy

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In our study, 48% of patients had DR of >10 years duration and 36% of 5–10 years duration. Furthermore, 87% of patients had uncontrolled diabetes (HbA1C >7). We also found a positive relationship between severity of diabetes (HbA1C) and duration of DM with the stage of DR [Figure 3].
Figure 3: Correlation between severity of diabetic retinopathy and control diabetes

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  Discussion Top

DR and DN are microvascular complications in which retina and glomerulus are affected respectively by similar pathophysiologic features in diabetes. Chronic hyperglycemia is the inciting factor.[13],[14] It causes progressive narrowing and eventual occlusion of vascular lumina, subsequently leading to inadequate perfusion of the affected tissue. In the retina, diabetes induces programmed cell death of Muller, ganglion cells, pericytes, and endothelial cells.[15] In the glomerulus, urinary protein loss and renal function decline are associated with widespread capillary occlusion and podocyte loss.

Several risk factors appear to influence susceptibility to the microvascular complications of DM, but the roles of genetic and environmental factors are not yet completely understood. In most of the previous studies, the prevalence of microvascular complications in patients with DM was evaluated along with their association with both univariate and multivariate regression analyses.[16] However, the relationship of one diabetic microvascular complication with another, to date, has not been clearly described in the Indian population. Although there has been consistent correlation showing association of risk factors like DM duration, poor glycemic control, arterial HTN, and poor lipid control with DR and DN,[17],[18] especially in Type 1 diabetics; however, the correlation is less evident in Type 2 diabetics with different prevalence rates.[19]

Pedro et al. showed that for DR, microalbuminuria is a good predictor for Type 1 DM but not for Type 2. However, their study showed a significant relationship of overt nephropathy with DR and macular edema in both types of diabetes.[20]

In the current study, 10 (62%) eyes in the group with microalbuminuria did not have any retinopathy changes. In the macroproteinuria group, a significant portion of patients' eyes, i.e., 61 (53%), showed mild-to-moderate NPDR. In massive proteinuria, 30 eyes of patients (48%) had PDR, which is again a significant number. Thus, there was a positive relationship found between proteinuria and retinopathy which was statistically significant. El-Asrar et al.[21] indicated that the prevalence of DN was found to rise with increasing severity of DR. Schmechel and Heinrich also indicated that the prevalence of proteinuria increased relative to the severity of DR in Type 1 and Type 2 DM.[22]

Also out of the total, CSME was present in 32 eyes (16%), most of which, i.e., 24 (75%), were in the macroproteinuria group. This is consistent with previous studies where the prevalence rates of DN was significantly higher among patients with DME when compared with those without DR.[21] However in a study by Lee et al., there was no significant association between CSME and DN, though they limited this finding by their smaller sample size, especially in patients with CSME.[23]

In addition, we found a significant relationship between HbA1C and both retinopathy and nephropathy as HbA1C assesses the glycemic control in diabetic, both in univariate and bivariate regression analyses. This result is consistent with previous studies where HbA1c, DM duration, and blood pressure were the most important risk factors.[24]

Similar previous studies showed diverse conclusions, and thus, they all were not consistent with the results of the current study. It may be due to differences in the study design, smaller sample size, or ethnic differences between east and western populations compared with the previous studies.

Our study concluded that the prevalence of diabetic retinopathy and maculopathy was more in patients with macroproteinuria and massive proteinuria than with microalbuminuria. Furthermore, a high prevalence of PDR was seen in patients with massive proteinuria. Thus, there was a positive correlation between diabetic retinopathy and nephropathy in Type 2 diabetics.

There also have been some previous studies that have reported the occurrence of DN and DR in isolation with no association between them.[25] This may be explained by fundamental differences in some patients and in pathogenesis. Further experimental studies would be required to investigate the exact differences in the pathophysiology of these diabetic microvascular complications.[26]

  Conclusions Top

A number of studies conducted on the western population provide evidence that DR is a powerful predictor for the progression of renal damage in DM patients, as it may be independently associated with the development of microalbuminuria.[21],[27],[28],[29] To the best of our knowledge, this is the first study evaluating the relationship between DR and DN in a Indian population and predicting the presence and severity of DR according to the severity of DN. The study suggests that patients with diabetic proteinuria must be carefully monitored for progressive eye disease, and timely evaluation should be done for a better prognosis. Thus, this study will help us to better understand the microvascular damage in diabetes and improve ways to screen, treat and control the disease.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3]


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