|Year : 1989 | Volume
| Issue : 1 | Page : 2-4
Genetic marker in juvenile diabetic retinopathy
PK Khosla, K Sharma, HK Tiwari, JS Bajaj, MC Vaidya
Department of Neuro-Ophthalmology, Sanjay Gandhi Post Graduate, Institute of Medical Sciences, Raebareli Road, Post Box 375, Lucknow 226 001, India
Department of Neuro-Ophthalmology, Sanjay Gandhi Post Graduate, Institute of Medical Sciences, Raebareli Road, Post Box 375, Lucknow 226 001
Source of Support: None, Conflict of Interest: None
Thirty five patients with insulin dependent diabetes mellitus (IDDM) were investigated for development of retinal microangiopathy by fluorescein angiography. HLA typing (A,B.C antigens) was done as a genetic marker. There was no statistically significant difference in the frequency of HLA antigens between patients without retinopathy (Gr.I) and with retinopathy (Gr.II) Frequency of various HLA antigens did not differ significantly in the mild and severe retinopathy groups or in comparison with controls. HLA B8 was significantly over represented in the patients of IDDM as a single group (GrI + II) when compared with controls (26% vs 8%). HLA profile was not a predictor of either the development or the severity of retinopathy in IDDM.
|How to cite this article:|
Khosla P K, Sharma K, Tiwari H K, Bajaj J S, Vaidya M C. Genetic marker in juvenile diabetic retinopathy. Indian J Ophthalmol 1989;37:2-4
|How to cite this URL:|
Khosla P K, Sharma K, Tiwari H K, Bajaj J S, Vaidya M C. Genetic marker in juvenile diabetic retinopathy. Indian J Ophthalmol [serial online] 1989 [cited 2020 Oct 24];37:2-4. Available from: https://www.ijo.in/text.asp?1989/37/1/2/26110
| Introduction|| |
The pathogenesis of diabetic microangiopathy remains poorly understood. Some diabetics remain free of complications after many years of inadequate control, while others develop complications like retinopathy relatively soon after the diagnosis of diabetes, indicating that factors others than diabetic control might be contributing to the risk of microangiopathy. Genetic factors seem to determine to a considerable extent the development of retinopathy in non-insulin dependent diabetes mellitus . In insulin dependent diabetes mellitus (IDDM, Juvenile diabetes), there is still a lot of controversy regarding the role of various factors in the pathogenesis retinopathy as of diabetes itself. The aim of the present study is to investigate the HLA system as a genetic marker for the development of juvenile diabetic retinopathy.
| Material and methods|| |
The study was carried out in 35 patients with juvenile diabetes (IDDM) and a group of 113 healthy normal subjects comparable in age and sex to the patients in the study. Patients with IDDM were divided into various groups depending on the severity of retinopathy . Group I- no retinopathy (20 patients); Group II-patients with retinopathy (15 patients) further divided into Group II a-mild retinopathy (6 patients), Group II a, II b -severe retinopathy (9 patients).
A detailed history and physical examination was done with regard to the duration of diabetes, family history, visual involvement, peripheral vascular disease, coronary artery disease and peripheral neuropathy. Detailed ophthalmological examination was carried out in each case including visual acuity, anterior segment examination, intraocular tension and fundus examination. Fluorescein angiography was done in all the cases of IDDM using Retinophot, Carl Zeiss (W. Germany) fundus camera with automatic robot equipment. Photographs of the disc and macula were taken at rapid sequence after injection of the dye. A late phase photograph was taken after an interval of 5 minutes.
Oral glucose tolerance test involved estimation of blood glucose, serum insulin (RIA) and C-peptide immunoreactivity using RIA kit (Novo Research Institute, Denmark) to test the beta cell function. IDDM was diagnosed by the severe loss of beta cell function and glucose intolerance. The patients and controls were HLA typed for A,B,C. loci by using two stage NIH microlymphocytotoxicity technique of Terasaki and McClelland .
Statistical analysis of the data was made by using Chi-square test (with Yate's correction) for sample size more than 30 and Fisher exact test for sample size less than 30.
| Observation|| |
Of the 35 patients of IDDM, 25 were males and 10 were females. The average age of onset of diabetes (at which the disease was diagnosed) and the duration of the disease are shown in [Table - 1]. While majority of the patients (53%) with retinopathy (Group II) had the disease for more than 10 years, the duration of the disease in 70% of patients without retinopathy (Group I) was less than 5 years.
Five out of 35 patients of IDDM had clinical evidence of peripheral neuropathy. There was no correlation between peripheral neuropathy and diabetic retinopathy (x 2= 3.29, not significant). One patient with severe retinopathy had large vessel disease which resulted in a below knee amputation. Results of ocular examination and fluoruscein angiography are shown in [Table - 2]. Extended oral GTT was done to characterize the type of diabetes. It involved serum immunoreactive insulin (IRI), serum C-peptide radio immunoreactivity (CPR) and blood glucose estimations at an interval of 30 minutes for 3 hours after 75 gm of glucose load. All the patients of IDDM showed loss of beta cell function indicated by severe carbohydrate intolerance with lower basal and post-glucose IRI and CPR as compared to normal controls.
HLA typing: Frequencies of various HLA antigens (A,B,C. loci) were studied in all the patients of IDDM (Gig 1 & 2). On statistical analysis, B8 was significantly over represented in patients of IDDM as a whole when compared with controls (26% vs 8%, p > 0.05). On comparison of the retinopathy group to the control, no significant over or under representation of any HLA antigen could be observed. No significant pattern of representation of HLA antigens could be revealed when the group of IDDM patients without retinopathy or with mild or severe retinopathy were compared with each other.
| Discussion|| |
The aetiopathogenesis of micro and macroangiopathic complications of diabetes presents a major challenge.
Relationship of the duration of diabetes and retinopathy: The mean duration of diabetes in Group I (no retinopathy) was 6.5 years; while in Group II (with retinopathy) it was 9 years. There was a trend towards increase in the frequency and, severity of retinopathy as the duration of the disease increased [Table - 1]. Some workers have reported that the frequency and severity of retinopathy is related to the duration of diabetes ,. Despite the fact that most patients after 15-20 years of overt diabetes develop retinopathy, unexplained is the fact that some juvenile diabetics never develop microangiopathic complications.  In the present study, 2 patients with no retinopathy (Group I) have had diabetes for 23 and 25 years respectively.
Retinopathy, neuropathy and peripheral vascular disease: In the present study, as has been reported by other workers,  there was no direct relationship between peripheral neuropathy and diabetic retinopathy. Correlation between retinopathy (microangiopathy) and big vessel disease (macroangiopathy) was also not very evident. 'In the multinational WHO study, diabetics from Japan and Hong Kong were relatively free from coronory artery and peripheral arterial disease, but the frequency of retinopathy and nephropathy was at least as high as in the most atherosclerotic diabetic populations. 
HLA and diabetic retinopathy : In the present study there was no significant difference in the frequency of various HLA antigens between the group of IDDM with and without retinopathy. There was no correlation either with the incidence or severity of retinopathy in IDDM. [Figure 1][Figure 2].
Several attempts have been made to answer the question of whether or not microvascular abnormalities like retinopathy are associated with particular HLA phenotypes. Becker et a1  reported in younger diabetics association of A1, B 8, B 15 and diabetes, with no further alterations in the patients with retinopathy. But these patients were not well characterized with regard to loss of beta cell function to diagnose IDDM, as has been done in our study.
Larking et al  in a small number of patients of IDDM with well characterized retinopathy showed an association between proliferative retinopathy and B8, when the latter was not associated with Al. Some other authors have also reported an association between B8 and severe diabetic retinopathy . In the present study patients of IDDM as a group showed statistically significant higher frequency (26%) of B8 as compared to controls (8%) but there was no association with the retinopathy.
Some workers have reported slightly increased frequency of B15 in IDDM patients with severe retinopathy , In our study, on the contrary the frequency of B 15 in IDDM patients as a group was quite low, with no correlation with retinopathy. Such negative correlation in north Indian juvenile diabetics has also been reported by other workers . Negative association between proliferative retinopathy and B7 & B 18 has been reported in IDDM , In our study, no patient with retinopathy was positive for B7 or B 18 but this negative association was not significant.
Though some reports suggest an association between HLA system and retinopathy in patients of IDDM, the evidence is not very definite. Recent data ,, which is based on well characterised and carefully selected patients of IDDM with and without retinopathy fails to show any HLA association with either incidence or severity of retinopathy. In subjects of IDDM, results of HLA-DR typing also do not suggest any correlation with the presence or absence of microangiopathy . Cudworth and Bodensky  have been unable to find any significant alteration in the frequency of non-HLA chromosome-6 genetic markers in patients of IDDM with complications.
Our present study does not suggest that in IDDM, development of retinopathy is dependent on HLA phenotypes. It is difficult to demonstrate a significant additional increase of any particular HLA specificity relating to a secondary aspect of diabetes when that particular antigen (i.e B8) is already associated with the basic susceptibility to develop IDDM.
| References|| |
Leslie, R.D.G., Barrette, A.H. and Pyke, D.A. Lancet. 1: 997, 1979
Leslie, R.D.G. and Pyke, D.A, Diabetes, 31:19, 1982.
Terasaki, P.I. and McClelland, J.D., Nature. 204:998, 1964.
Mild, E., Akanuma, Y., Kasaka, K., In frontiers in Diabetes Microangiopathy,3:285, 1983.
Pirart, J., Diabetes Care, 1:168, 1978
Bolande, R.P., Perspect. Pediatr. Pathol, 5:269, 1979.
Blood worth, J.M.B. and Greider, M. Endocrine Pathology, General and surgical : Bloodworth, J.M.B (Ed.) p. 556, 1982.
Jarret, R.J. and Keen II., Diabetes Care, 2:196, 1979.
Becker, 13., Shin, D.II., Burgess Des al Diabetes, 26:997, 1979.
Larkins, R.G., Martin, F.I.R. and Tait, B.D., BMJ, 1:111, 1978.
Standl, E., Dextel, T., Lander, T., Albert, E.D., and Scholz, S., Diabetologia, 18.79, 1980.
Barbosa, J., Noreen, II., Emmel, L. et al, Tissue Antigens, 7:233, 1976.
Moller, E, Person, B. and Sterky, G., Diabetologia. 14:155, 1978.
Srikanta, S., Mehra, N.K., Vaidya, M.C., Malaviya, A.N., Clinical and Experimental, 30:992,1981.
Standle, E., Dexel, T., Alberti, E.D., et al, Diabetes, 28:396,1979.
Cove, D.I I., Wlaker, LM., Mackintosh, P., Wells, L., Wright, d.D., Diabetologia, 19:402, 1980
Johnston, P.B. Kidda, M., Middleton, D., Greenfield, A.A., Archer, D.B., Maguire, C.J.F. and Kennedy, L., Br. J. Opthalmol., 66:277, 1982.
Mimura, G., Putenma, H. and Sakamoto, Y., Frontier in Diabetes, Microangiopathy, Belior, F.(Ed). 3:365,1983.
Bodansky, II.J., Wolf, E., Cudworth, A.G., et al, Diabetes, 31:70,1982.
Bodansky, Iii., Drury, P.L., Cudworth A.G. et al, Diabetes. 30: 907, 1981.
[Table - 1], [Table - 2]
|This article has been cited by|
||Genetics of diabetic retinopathy: Study of VEGF gene
| ||Bazzaz, J.T., Pravica, V., Boulton, A.J.M., Hutchinson, I.V. |
| ||Iranian Journal of Diabetes and Lipid Disorders. 2006; 5(3): e22 |
||Diabetic retinopathy and HLA antigens in type 2 diabetes mellitus
| ||Birinci, A., Birinci, H., Abidinoglu, R., Durupinar, B., Öge, I. |
| ||European Journal of Ophthalmology. 2002; 12(2): 89-93 |
||Genetic markers in early diabetic retinopathy of adolescents with type I diabetes
| ||Falck, A.A.K., Knip, J.M., Ilonen, J.S., Laatikainen, L.T. |
| ||Journal of Diabetes and its Complications. 1997; 11(4): 203-207 |