Prevalence of Retinopathy Detected by Fundoscopy among Newly Diagnosed Type 2 Diabetic Patients Visiting a Local Hospital in Lahore

Tasnim Farasat*, Saima Sharif, Farkhanda Manzoor, Muneeza Zafar and Shagufta Naz

Department of Zoology, Lahore College for Women University, Jail Road, Lahore.

ABSTRACT

The cross-sectional study was conducted on 200 newly diagnosed diabetic patients to assess the prevalence of diabetic retinopathy and to evaluate its relationship with potential risk factors of diabetes on their first visit to a local hospital. Among the newly diagnosed diabetic subjects 33% (n=66) were with retinopathy. Out of which 30% (n=18) were male and 70% (n=48) were female. High density lipoprotein (HDL), both systolic and diastolic blood pressure, cholesterol level and serum insulin were significantly higher (p< 0.05) in proliferative group of diabetic retinopathy, while triglyceride level, HbA1c (%), and low density lipoprotein (LDL) were non-significantly higher (p> 0.05) in diabetic retinopathy groups. To conclude high prevalence of diabetic retinopathy was observed among newly diagnosed diabetic patients.

Article Information

Received 01 April 2015

Revised 02 May 2016

Accepted 09 August 2016

Available online 10 January 2017

Authors’ Contributions

TF conceived and designed the project. MZ executed experimental work. SS and TF compiled the results and wrote the article. SN and FM analyzed the data.

Key words

Fundoscopy, Retinopathy, Proliferative, BDR, Type 2 diabetes.

* Corresponding author: [email protected]

0030-9923/2017/0001-0367 $ 9.00/0

Copyright 2017 Zoological Society of Pakistan

DOI: http://dx.doi.org/10.17582/journal.pjz/2017.49.1.367.372

INTRODUCTION

An increase in the incidence and prevalence of diabetes mellitus and its complications have been observed in recent decades (Kollias and Ulbig, 2010). In Pakistan according to the National Health Survey the prevalence of impaired glucose tolerance (IGT) and diabetes among the population age >25 years, is 22.4% (Shera et al., 2010). Diabetic patients are also susceptible to acute and chronic complications such as retinopathy (Wild et al., 2004). Diabetic retinopathy (DR) is a microangiopathy of the retina, in which the visual acuity is lost when the area of the sharpest vision on the retina is affected severely by the pre or intraretinal hemorrhages, macular edema, retinal tractional and detachment, or due to loss of capillaries of the peripheral loop network (Kollias and Ulbig, 2010). In the USA, an estimated 40% (8% for vision-threatening retinopathy) of people with type 2 diabetes and 86% (42%) with type 1 diabetes have DR (Kempen et al., 2004; Roy et al., 2004). The low prevalence rates of DR have been reported in some developing countries e.g., India (17%) (Rema et al., 2005; Raman et al., 2009). In South East Asia, data from Singapore showed that 34% of Asian Malay adults with diabetes had signs of retinopathy and 10% had vision threating retinopathy (Wong et al., 2008). In Pakistan the overall DR prevalence is 15.3% (Shaikh et al., 2008). Background diabetic retinopathy is named appropriately because it sits in the background, not itself a danger to vision, but is instead a warning sign that serious damage may be starting (Watkins, 2003). In non-proliferative DR, the outward ballooning of the capillary wall occurs which is also known as micro aneurysms. They are detected by opthalomoscopy. The pre-proliferative stage, which is characterized by worsening of retinal ischemia, lead to formation of new vessels (neo-vascularization). It is characterized by the presence of one of the following: Multiple large dark blot hemorrhages, multiple (more than 5) cotton wool spots appearing as dead white patches with vague margins and representing micro-infarcts in the nerve fiber layer, Venous bleeding, looping, duplication and intraretinal micro-vascular abnormalities (IRMA).In proliferative diabetic retinopathy (PDR), the diffusion of the capillary bed becomes more severe and spread across the retinal-area. There are several risk factors, which are responsible for the occurrence and progression of diabetic retinopathy. The basic risk factors are hypertension, duration of disease and quality of glycemic control, hyperlipidemia, HbA1c level, and surgery for premature cataracts in diabetic patients (Wong and Mitchell, 2007; Kollias and Ulbig, 2010). Insulin is an important anabolic hormone which stimulates the proliferation of vascular endothelium, so insulin resistance is also an important risk factor for its proliferation. Type 2 diabetes usually remains asymptomatic before the onset of frank diabetes and its clinical diagnosis. The current study aimed to evaluate the prevalence of DR at the time of clinical diagnosis of diabetes mellitus because microvascular complications are directly related to the duration of diabetes mellitus, and early detection of retinopathy is an important preventative strategy for the visual impairment in diabetic patients on their visit first to a diabetic centre. In the UK Asian diabetes study researchers showed that after controlling for retinopathy risk factors people with a south Asian origin were more likely to have diabetic retinopathy than were white people (Raymond et al., 2009).

The basic aim of this study was to find the DR prevalence and evaluate the potential risk factors including blood pressure, HbA1c, lipid profile serum insulin and insulin resistance in the progression of DR among newly diagnosed type 2 diabetic subjects.

MATERIALS AND METHODS

This cross-sectional study was conducted on 200 newly diagnosed diabetic subjects from January 2010 to June 2010 who visited the Amin-Hayyat Memorial Trust Hospital first time. It is an outpatient diabetic clinic for low income people. Impaired glucose tolerance (IGT) and hyperglycemic state remained undiagnosed for a long period when they first visited the hospital, the retinopathy condition was diagnosed. During the study period 250 subjects were diagnosed as hyperglycemic on the basis of American Diabetic Association criteria as for FBG > 126mg. They were informed verbally to visit the clinic after 12 h fast for detailed checkup. Out of the 250 subjects 200 were responders and 50 were non-responders who refused to eye examination and blood test. All the subjects in the study completed a questionnaire that included information about the subject’s age, personal habits (smoking or alcohol consumption), family history of diabetes and socioeconomic status. They all belonged to a low socioeconomic class. Biochemical laboratory tests were performed, included both fasting and random blood glucose levels, lipid profile and HbA1c by using Hitachi 902 biochemical analyzer and insulin resistance was calculated by HOMA IR. A consultant ophthalmologist of the hospital carried out detailed eye examination by using Top con Ophthalmoscope. DR was diagnosed on the basis of presence of lesions like micro-aneurysms, clinically significant macular edema, venous bleading and occasional dot blot hemorrhages. The presence of retinopathy was assessed by fundoscopy after dilating the pupil. DR was clinically graded according to the retinopathy disease severity scale (Wilkinson et al., 2003) as: i) No abnormality and no apparent retinopathy (Normal); ii) increased vascular permeability (BDR); iii) Pre-proliferative stage (Aneurism) and iv) Proliferative stage (Neovascularization, Multiple Hemorhages).

Monobind insulin ELISA kit was used for the quantitative determination of insulin in human serum.

Statistical analysis

The mean ± SEM values of demographic and biochemical parameters of each group was calculated. The difference between the groups and with in the groups was done by ANOVA followed by Tukey test. All the statements of significance are based on 0.5 % level of significance. Statistical analysis was done by using SPSS version 13.0 (IL, Chicago).

RESULTS

Out of the total responders 200 diabetic subjects, 40% (n=80) were males and 60% (n=120) were females. The total number of retinopathic subjects were 33% (n=66) and normal subjects were 67% (n=134). Out of the total 33% retinopathic subjects, 20% (n=40) were belonging to BDR group, 7% (n=14) were at preproliferative stage and 6% (n=12) were at the proliferative stage.

The characteristics of the study population are summarized in Table I. No difference in the mean age was observed among the groups. ANOVA followed by Tukey test revealed that both proliferative and BDR groups have

Table I.- Demographic and Biochemical characteristic of the study population in control and diabetic retinopathic subjects.

significantly higher values of FBG (p < 0.05) when compared with normal group while pre-proliferative stage has non-significantly higher values when compared with normal fundoscopic group. Random blood glucose (RBG) was significantly higher in proliferative group when compared with normal (p < 0.05). The difference among the pre-proliferative group and BDR group was non-significant (p > 0.05). The difference of HbA1c between and within the groups was non-significant (p > 0.05). Serum Insulin levels also had a significant difference among the groups (p < 0.05). The difference of systolic blood pressure among the normal group and proliferative group was significant (p <0.05) whereas in other groups difference was non-significant. The difference of diastolic blood pressure among the groups was significant (p < 0.05). The difference in total cholesterol between pre-proliferative group and proliferative group was significant (p < 0.05) while the difference of the BDR group with normal group was non- significant. In triglyceride the differences among the groups were non-significantly higher (p > 0.05). HDL had non-significant difference between the groups (p > 0.05). The difference of LDL between proliferative group and BDR groups was significant (p < 0.05) while the difference between the pre-proliferative group and BDR was non-significant (p > 0.05). Significant difference among the groups was observed in the values of fasting serum insulin (Table I). Significant differences were observed for diabetes related parameters according to the presence of DR stage. The significant clinical parameters included random blood glucose, HbA1c, Diastolic blood pressure and lipid profile.

DISCUSSION

It was reported by Farasat et al. (2009) that 58% subjects were found undiagnosed of their diabetic status on their first visit to hospital. In this study the diabetic subjects were clinically evaluated by fundoscopy after diagnosis of diabetes. According to our study the prevalence of diabetic retinopathy was very high (33%) as compared to international and national data. According to pilot studies in Pakistan the prevalence of diabetic retinopathy is between 26.1% and 33.3% (Kayani et al., 2003). Similarly high prevalence estimates have been reported in other countries (Raymond et al., 2009).

In this study the fasting and random plasma glucose was significantly associated with advanced stage of retinopathy i.e. Proliferative DR. Hyperglycemia increases production of reactive oxygen species (free radical) leading to the activation of protein kinase C formation of advanced glycation end products contributing to vascular endothelial damage.

These results were similar as compared to other multiple studies in which higher FBG level was associated with diabetic retinopathy. The results of random blood glucose were also similar with findings of Reichard et al. (1993). Our finding about HbA1c level revealed that it was significantly associated (p < 0.05) with retinopathy stage detected by fundoscopy. These results were similar to other observational studies which reported that the glycated hemoglobin significantly increased with the severity of diabetic retinopathy (Klein et al., 1994; Lloyed et al., 1995). Significant association of glycated hemoglobin might be attributed due to the prolonged duration of hyperglycemia among these newly diagnosed diabetic subjects. The study population belonged to low socioeconomic status, the hyperglycemia remained undiagnosed and when they approached the clinic persistent hyperglycemic condition damaged the retina resulting in retinopathy.

According to the present study the concentration of serum insulin and insulin resistance were significantly high with the progression and proliferation of diabetic retinopathy. In persistent undiagnosed hyperglycemia diabetes might reduce insulin receptor signaling in the retina leading to neurodegeneration and damage to the retina (Curtis et al., 2009). The differences between all the groups were significant as (p < 0.05). These results were similar with Gwinip and Elias (1991) who reported increased concentration of serum insulin in the advanced stages of the retinopathy. The blood pressures both systolic and diastolic were significantly high with the advancement of retinopathic stage. Hendrick et al. (2002) reported that the increasing blood pressure is associated with increased proliferation in diabetic retinopathy. Other studies done in different countries in Iran, India and in Denmark also revealed the similar results and concluded that the blood pressure is an important risk factor for the progression and proliferation of diabetic retinopathy (Hov et al., 2004; Abdollahi et al., 2006; Agarwall et al., 2006). In the present study the total cholesterol level was significantly higher with the progressive diabetic retinopathy. The results were in agreement with Wahab et al. (2008) who reported that an increased cholesterol level was associated with retinopathy. The mean value of HDL cholesterol decreased during the subsequent stages of retinopathy with a significant difference in the progressive stages of retinopathy (p<0.05). These results were in contrast to Kordonouri et al. (1996) who reported that the level of HDL was significantly higher in the diabetic retinopathy (p < 0.05). In present study the LDL cholesterol concentration increased as the proliferation of retinopathy increased. The difference in the mean values of LDL between the groups was significant (p < 0.05). These results were also in agreement with Kostraba et al. (1991) who reported an increase in LDL cholesterol with progression of PDR in a multivariate analysis. Two other studies done by Wahab et al. (2008) and Hendrick et al. (2002) had revealed that LDL cholesterol is an important risk factor the diabetic retinopathy. The mean values of triglycerides in the present study, showed an increasing trend for triglyceride level in subsequent stages of diabetic retinopathy.

There are conflicting reports in the literature regarding the effect of lipid profile on retinopathy. In a study by Lyons et al. (2004) observed that severity of retinopathy was associated with increasing triglycerides and inversely associated with HDL cholesterol. It was reported by Keech et al. (2006) that intensive glycemic control and combination treatment of dyslipidemia reduced the rate of progression of DR. In another study it was reported that serum lipids may have a strong influence only in the severe forms of diabetic retinopathy that involved the pathogenesis only via exudation of lipids through damaged retinal vasculature and breakdown of the blood retinal barrier (Benarous et al., 2011). On the contrary Hove et al. (2004) in a study conducted in Denmark reported no significant association between DR, triglycerides, HDL and total cholesterol in the diabetic population. In another study, there was no association between DR and lipid profile, however, clinically significant macular edema was found to be associated with serum lipids (Benaraus et al., 2011). Although all ethnic groups are susceptible to the established risk factors of DR such as duration of the disease, severity of hyperglycemia, dyslipidemia and hypertension, Significant differences in the prevalence and severity of DR and Diabetic macular edema between different ethnic groups has been reported (Wong et al., 2006; Sivaprasad et al., 2012). This population represented a low income group without any management of diabetes and medical care. A high %age of HbA1c in these newly diagnosed groups indicates chronic hyperglycemia and other causal factors, including dyslipidemia and consistent hypertension that initiated a cascade of biochemical and physiological changes that lead to the manifestation of microvascular damage and diabetic retinopathy.

CONCLUSION

The results of present study revealed high percentage (33 %) of diabetic retinopathy among newly diagnosed type 2 diabetic patients that underscores the need for fundoscopic examination in newly diagnosed diabetic patients.

Statement of conflict of interest

Authors have declared no conflict of interest.

REFERENCES

Abdollahi, A., Malekmadani, M. H., Mansoori, M.R., Bostak, A., Abbaszadeh, M.R. and Mirshahi, A., 2006. Prevalence of diabetic retinopathy in patients with newly diagnosed type II diabetes mellitus. Acta med. Iran, 44: 415–419.

Agarwal, S., Raman, R., Kumari, R.P., Deshmukh, H., Paul, P.G. and Gnanamoorthy, P., 2006. Diabetic retinopathy in type II diabetics detected by targeted screening versus newly diagnosed in general practice. Annl. Acad. Med., Singapore, 35: 531-535.

Benarous, R., Sasongko, M.B., Qureshi, S., Fenwick, E., Dirani, M., Wong, T.Y. and Lamoureux, E.L., 2011. Differential association of serum lipids with diabetic retinopathy and diabetic macular edema. Invest. Ophthalmol. Vis. Sci., 52: 7464–7469. https://doi.org/10.1167/iovs.11-7598

Curtis, T.M., Gardiner, T.A. and Stitt, A.W., 2009. Microvascular lesions of diabetic retinopathy: clues towards understanding pathogenesis? Eye, 23: 1496–1508. https://doi.org/10.1038/eye.2009.108

Farasat, T., Cheema, A.M. and Khan, M.N., 2009. Correlation among BMI, fasting plasma glucose and HbA1c levels in subjects with glycemic anomalies visiting diabetic clinics of Lahore. Pakistan J. Zool., 41: 173-178.

Gwinp, G. and Elias, A.N., 1991. Hypothesis: insulin is responsible for vascular complications of diabetes. Med. Hypoth., 34: 1- 6. https://doi.org/10.1016/0306-9877(91)90056-5

Hendrick, A., Leiden, V., Jacqueline, M., Annette, C., Nijpels, G., Robert, J., Lex, M., Coen, D.A. and Bettine, C.P., 2002. Blood pressure, lipids, and obesity are associated with retinopathy. Diabet. Care, 25: 1320-1325. https://doi.org/10.2337/diacare.25.8.1320

Hove, M.N., Kristensen, J.K., Lauritzen, T. and Bek, T., 2004. The prevalence of retinopathy in an unselected population of type 2 diabetes patients from Arthus County, Denmark. Acta Ophthalmol. Scand., 82: 443–448. https://doi.org/10.1111/j.1600-0420.2004.00270.x

Kayani, H., Rehan, N. and Ullah, N., 2003. Frequency of retinopathy among diabetics admitted in a teaching hospital of Lahore. J. Ayub Med. Coll. Abbottabad, 15: 53-56.

Keech, A.C., Mitchell, P., Summanen, P.A., O’Day, J., Davis, T.M., Moffitt, M.S., Taskinen, M.R., Simes, R.J., Tse, D., Williamson, E., Merrifield, A., Laatikainen, L.T., D’emden, M.C., Crimet, D.C., O’Connell, R.L. and Colman, P.G., 2006. Field study investigators Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomized controlled trial. Lancet, 370: 1687–1697. https://doi.org/10.1016/S0140-6736(07)61607-9

Kempen, J.H., O’Colmain, B.J. and Leske, M.C., 2004. The prevalence of diabetic retinopathy among adults in the United States. Arch. Ophthalmol., 122: 552–563. https://doi.org/10.1001/archopht.122.4.552

Wild, S., Roglic, G., Green, A., Sicree, R. and King, H., 2004. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabet. Care, 27: 1047–1053. https://doi.org/10.2337/diacare.27.10.2569-a

Klein, R., Klein, B.E K., Moss, S.E. and Cruickshanks, K.J., 1994. The Wisconsin epidemiologic study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch. Ophthalmol., 112: 1217-1228. https://doi.org/10.1001/archopht.1994.01090210105023

Kollias, N.A. and Ulbig, W.M., 2010. Diabetic retinopathy. Dtsch. Arztebl. Int., 107: 75-84.

Kordonouri, O., Danne, T., Hopfenmuller, W., Enders, I., Hovener. G. and Weber, B., 1996. Lipid profiles and blood pressure: are they risk factors for the development of early background retinopathy and incipient nephropathy in children with insulin-dependent diabetes mellitus? Acta Paediat., 85: 43-48. https://doi.org/10.1111/j.1651-2227.1996.tb13888.x

Kostraba, J.N., Klein, R. and Dorman, J.S., 1991. The epidemiology of diabetes complications study. IV. Correlates of diabetic background and proliferative retinopathy. Am. J. Epidemiol., 133: 381-391.

Lloyd, C.E., Klein, R., Maser, R.E., Kuller, L.H., Becker, D.J. and Orchard, T.J., 1995. The Pittsburgh epidemiology of diabetes complications (EDC). Study. J. Diab. Comp., 9: l40-l48. https://doi.org/10.1016/1056-8727(94)00039-Q

Lyons, T.J., Jenkins, A.J., Zheng, D., Lackland, D.T., McGee, D., Garvey, W.T. and Klein, R.L., 2004. Diabetic retinopathy and serum lipoprotein subclass in DCCT/EDIC cohort. Invest. Ophthalmol. Vis. Sci., 45: 910-918. https://doi.org/10.1167/iovs.02-0648

Raman, R., Rani, P.K., Reddi, S., 2009. Prevalence of diabetic retinopathy in India: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study Report 2. Ophthalmology, 116: 311–318. https://doi.org/10.1016/j.ophtha.2008.09.010

Raymond, N.T., Varadhan, L. and Reynold, D.R., 2009. Higher prevalence of retinopathy in diabetic patients of South Asian ethnicity compared with white Europeans in the community: a cross-sectional study. Diabetes Care, 32: 410–415. https://doi.org/10.2337/dc08-1422

Reichard, P., Nilsson, B.Y. and Rosenqvist, U., 1993. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N. Engl. J. Med., 329: 304-309. https://doi.org/10.1056/NEJM199307293290502

Rema, M., Premkumar, S., Anitha, B., Deepa, R., Pradeepa, R. and Mohan, V., 2005. Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural Epidemiology Study (CURES) eye study, I. Invest. Ophthalmol. Vis. Sci., 46: 2328–2333. https://doi.org/10.1167/iovs.05-0019

Roy, M.S., Klein, R., O’Colmain, B.J., Klein, B.E., Moss, S.E. and Kempen, J.H., 2004. The prevalence of diabetic retinopathy among adult type 1 diabetic persons in the United States. Arch. Ophthalmol., 122: 546–551. https://doi.org/10.1001/archopht.122.4.546

Shaikh, A., Shaikh, F., Shaikh, A.Z. and Ahmed, J., 2008. Prevalence of diabetic retinopathy and influence factors among newly diagnosed diabetics in rural and urban areas of Pakistan. Pak. J. med. Sci., 24: 774-779.

Shera, S., Basitb, A., Fawwadc, A., Hakeemc, H., Ahmedanic, Y.M., Zafar, M., Hydrieced, I. and Khwajaa, I.A., 2010. Pakistan national diabetes survey: prevalence of glucose intolerance and associated factors in Punjab Province of Pakistan. Prim. Care Diabetes, 4: 79-83. https://doi.org/10.1016/j.pcd.2010.01.003

Sivaprasad, S., Gupta, B., Crosby, N.R. and Evans, J., 2012. Prevalence of diabetic retinopathy in various ethnic groups: a worldwide perspective. Surv. Ophthalmol., 57: 347–370. https://doi.org/10.1016/j.survophthal.2012.01.004

Wahab, S., Mahmood, N., Shaikh, Z. and Kazmi, H.K., 2008. Frequency of retinopathy in newly diagnosed type 2 diabetes patients. J. Pak. med. Assoc., 58: 557-561.

Watkins, P.J., 2003. ABC of diabetes-Retinopathy. Br. med. J., 326: 924-926. https://doi.org/10.1136/bmj.326.7396.977

Wilkinson, C.P., Ferris, F.L,, Klein, R.E., Lee, P.P., Agardh, C.D., Davis, M., Dills, D., Kampik, A., Pararajasegaram, R. and Verdaguer, J.T., 2003. Global diabetic reti­nopathy project group. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology, 110: 1677-82. https://doi.org/10.1016/S0161-6420(03)00475-5

Wong, T.Y. and Mitchell, P., 2007. The eye in hypertension. Lancet, 365: 525–635. https://doi.org/10.1016/b978-0-323-03961-1.50054-4

Wong, T.Y., Cheung, N. and Tay, W.T., 2008. Prevalence and risk factors for diabetic retinopathy: the Singapore Malay Eye Study. Ophthalmology, 115: 1869–1875. https://doi.org/10.1016/j.ophtha.2008.05.014

Wong, T.Y., Klein, R., Islam, F.M., Cotch, M.F., Folsom, A.R., Klein, B.E., Sharrett, A.R. and Shea, S., 2006. Diabetic retinopathy in a multi-ethnic cohort in the United States. Am. J. Ophthalmol., 141: 446–455. https://doi.org/10.1016/j.ajo.2005.08.063