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ORIGINAL ARTICLE |
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Year : 1989 | Volume
: 37
| Issue : 1 | Page : 5-7 |
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Growth hormone and diabetic retinopathy
R Singh, JK Agrawal, V Kumar, RD Raman, OPS Maurya
C-7, New Medical Enclave, Banaras Hindu University, Varanasi - 221 005, India
Correspondence Address: R Singh C-7, New Medical Enclave, Banaras Hindu University, Varanasi - 221 005 India
Source of Support: None, Conflict of Interest: None | Check |
PMID: 2807507
Growth hormone has been considered to be the cause of diabetic retinopathy. However the relationship between growth hormone responses and diabetic retinopathy has not been consistent. Moreover, the correlation (if any) between the severity of retinopathy and growth hormone changes are also not well defined. In the present study 23 diabetics (16 with retinopathy, 7 without retinopathy) and 8 non-diabetic healthy controls were studied. Serum growth hormone was measured in the fasting state and one hour after levodopa administration. The mean growth hormone levels were significantly higher in the diabetics as compared to controls, however there was no correlation between the mean growth hormone levels (either in the fasting state or after levodopa stimulation) and presence or absence of diabetic retinopathy although diabetics with retinopathy had significantly greater mean growth hormone response. The mean growth hormone was found to have no correlation with the fasting blood sugar levels. Diabetics with back ground retinopathy had significantly greater mean growth hormone levels than those with proliferative retinal changes
How to cite this article: Singh R, Agrawal J K, Kumar V, Raman R D, Maurya O. Growth hormone and diabetic retinopathy. Indian J Ophthalmol 1989;37:5-7 |
Introduction | | |
Serum growth hormone (GH) abnormalities in diabetics have long suggested to be responsible for the retinal changes [1],[2],[3],[4].This casual association has further been supported by the relative infrequency of retinopathy in diabetics with growth hormone deficient states [5],[6].Knoph and co-workers [7] observed significantly higher mean fasting growth hormone concentrations in diabetic with retinopathy than those without the retinal changes. Passa and his associates [8] demonstrated exaggerated growth hormone responses to muscular exercise in patients with diabetic retinopathy. However, such a correlation could not be established between the levodopa stimulated growth hormone response and the presence or absence of diabetic retinopathy [9].Moreover, the relationship between growth hormone responses and the severity of diabetic retinopathy is also not well defined.
In the present work, fasting and levodopa stimulated growth hormone responses have been studied in diabetes with and without retinopathy as well as in normal healthy controls. Further, the growth hormone response has also been correlated with the severity of diabetics and the grade of diabetic retinopathy.
[TAG:2]MATERIAL & METHODS[/TAG:2]
Twenty three diabetic patients and 8 age matched healthy controls have been studied. The diabetic state was confirmed on fasting blood sugar (FBS) levels (140 mg) or after an oral glucose tolerance test (OGTT) [10].The controls were selected from the persons attending the ophthalmic out patient for refractive errors. In them also diabetes mellitus was excluded by OGTT. The diabetic retinal changes were graded according to the criteria of Schie and Albert [11].The duration of diabetes was ascertained on the basis of history of definitive symptoms and/or previous FBS or OGTT results. The patients with FB S level of more than 200mg. per cent were considered to be severely diabetic and those having values below this level were considered mildly diabetic. The diabetic state was considered to be under good controls of the fasting blood sugar value was between 100-120mg per cent and/or postprandial blood sugar values were between 160-180mg per cent. Serum growth hormone levels were estimated in the fasting state and one hour after oral levodopa (500mg) administration [12].The levodopa was given in the fasting state. The radioimmune essay of growth hormone was done using dextran coated Charcoal [13]
Results | | | :
Amongst the 23 diabetics studied, retinal changes were found in 16 (69.5%) patients. In the remaining 7(30.5%), the fundus was normal. The mean age of diabetics with and without retinopathy was 52.8±11.5years and 49.3±8.5 years, while that of the controls was 46.4±6.7 years, respectively.
Duration and Severity of Diabetes and Retinopathy
The duration of diabetes was less than 5 years in 56.5% and in the remaining it was more than 5 years. The diabetic state was mild (FBS (200 mg%) in 30.4% and severe (FBS - 200 mg%) in the remaining 69.6%. The frequency of retinopathy was found to have no correlation either with the duration or the severity of the disease.
Serum Growth Hormone and Retinopathy:
The mean growth hormone levels in the fasting state as well as after the levodopa stimulation were significantly higher in diabeties with and without retinopathy (p/_ 0.01) as compared to healthy controls. However, in between the two diabetic groups there were no statistical differences [Table - 2]. But diabetics with retinopathy had greater (p/-0.05) mean growth hormone response to levodopa as compared to controls, than those without retinopathy.
Growth Hormone Response and Severity of Diabeties and Retinopathy
The mean growth hormone response after levodopa administration was found to be statistically similar in patients with fasting blood sugar values below or above 200mg percent, whereas diabetics with background retinopathy had significantly greater (p/-0.01) response than those with proliferative retinal changes.
Comments
In the pathogenesis of diabetic retinopathy, many factors have been implicated [14].Lundback et al [2],[3] while observing high and fluctuating levels of growth hormone considered it to be the main cause of diabetic angiopathy and retinopathy. The infrequency of retinal involvement in growth hormone deficient dwarfs having poor growth hormone responses [6] favors such a concept.
Some studies [15],[16],[17],[18] demonstrated elevated growth hormone levels in patients with diabetes mellitus. Hansen [17],[18] in addition, mentioned, that response to exercise occurs earlier and is greater in diabetics that that in the normal subjects. Knopf and workers [7] observed significantly higher mean fasting growth hormone concentrations in diabetics with retinopathy than those without it. Passa and his associates [8] described significantly greater growth hormone response to muscular exercise in patients with diabetic retinopathy only. Holland et al [9] however, could not correlate levodopa stimulated growth hormone response with the presence or absence of retinopathy. In the present study also, the mean serum growth hormone concentrations both in the fasting state (Group A : P/-0.01; Group B : P/-0.01) as well as after the levodopa stimulation (Group A : P/-0.01; Group B : P/-0.01) were significantly higher in the diabetic groups as compared to the normal healthy controls. But these were statistically similar in diabetics with and without retinopathy. The mean growth hormone response to levodopa was, however, significantly greater (P/-0.05) in patients with retinopathy only [Table - 2].
Although, abnormal growth hormone dynamics in diabetics have been correlated with blood sugar levels in the reported patient, no such association could be established. The man growth hormone was similar in patients with FBS levels below or above 200mg per cent. The severity of retinopathy however, was found to be a significant determinant of growth hormone response as patients with background retinopathy had significantly greater (P/-0.05) mean values, than those with proliferative retinal changes [Table - 3]. To explain this association, if has been proposed that the elevated growth hormone levels in diabetics, enhances fatty acid catabolism with accumulation of sorbitol leading to basement membrane thickening and other changes secondary to sorbitol accumulation [21]. Alternatively other growth hormone dependent mechanisms, viz. hepatic synthesis of large plasma proteins including fibrinogen and alpha-2 globulins [19]sub , altered basement membrane glycoprotein synthesis [22] and accelerated platelet aggregation secondary to changes in von-Willebrand factor activity [23], have also been suggested. However, the precise biochemical mechanism of growth hormone action and its role in the pathogenesis of diabetic retinopathy still remains unclear.
References | | |
1. | Powell, E.D.V.; Frantz, A.G.; Ralkin, M.T. et al: Growth hormone in relation to diabetic retinopathy. New Eng. J. Med. 275, 922 |
2. | Lundback, K.; Christensen, N.J.; Jenson, V.A. et al: Diabetes, Diabetic Angiography and Growth Hormone. Lancet, 2:131, 1979. |
3. | Lundback, K; Christensen, N.J.; Jenson, V.A. et al: The pathogenesis of Diabetic Angiopathy and Growth Hormone. DMiish. Bull 18:1, 1971. |
4. | Luft, R. and Guillemin, R. : Growth hormone and diabetes in man. Old concept - New implications. Diabetes, 23:273, 1974. |
5. | Merimee, T.J.; Fineberg, S.E. and Hollander, W.Vascular Diseases in the Chronic Growth Hormone Deficient State. Diabetes, 22:813, 1973. |
6. | Passa, P.; Rousselie, F. Gauville, C. et al. : Retinopathy and plasma growth hormone levels in idopathic haemochromatosis with diabetes. Diabetes, 26:113, 1977. |
7. | Knoph, H.F.; Fajan, S.S.; Floyd, J.C. et al. : Elevated 'casual' fasting levels of growth hormone in patients with diabetic retinopathy. Diabetes. 21 (Suppl;, 1) 322, 1972 |
8. | Passa, P.; Granville, C. and Caniveb, P. : Influence of muscular exercise on plasma levels of growth hormone in diabetes with and without retinopathy. Lancet 2:27, 1974. |
9. | Holland, P.M.; Landers, M.B. III, Lebovitz, A.E. et al. : Levodopa stimulated growth secretion and diabetic retinopathy. Amer. J. Ophthal. 82:62, 1976 |
10. | Fajan, S.S. and Conn, J.W. : Early diagnosis of diabetes. Ann.N.Y. Acad. Sci. 82:208, 1959. |
11. | Schie, H.G. and Albert, DMS : In text book of ophthalmology W.B. Saunders, New York, 1977. |
12. | Lin,T. and Tucci,H. :Provocative tests of growth hormone release. A comparison of results with seven stimuli Ann. Inst. Med. 80:464, 1974. |
13. | Meek,J.C.;Stoskoph,M.M.andBotinger,R.E.:Optimizationofradioimmunoassay for human growth hormone by charcoal sixtra technique. Clin. Chem. 16:845, 1970. |
14. | Kohner, E.M. and Dollery, C.T. : Diabetic retinopathy : In complication of diabetes. Edited by H. and J. Jarret, pp. 7-98, Edward Arnold, London, 1975. |
15. | Johansen, K. and Hansen, A.P. : High 21 hour level of plasma growth hormone in juvenile diabetics. Brit. Med. 1.2:356, 1969. |
16. | Hazen, T.C.; Lawren, A.M. and Kristein, L. : Abnormal G.H. secretion in ketosis prone diabetes. J.Lab. Med. Clin. 78:993, 1971. |
17. | Hansen, A.P. :Abnormal serum growth hormone response to exercise in Juvenile diabetics. J.Clin. Invest. 43:1467, 1973. |
18. | Hansen, A.P. : Abnormal serum growth hormone response to muscular exercise in maturity onset diabetes. Diabetes, 22:619, 1973. |
19. | Little, H.L.: Role of abnormal hemorrheic dynamics in the pathogenesis of diabetic retinopathy. Trans. Amer. Ophthal. Sec. 74:573, 1976. |
20. | Hansen, A.P. : Normalization of Growth Hormone Hyper response to exercise in Juvenile Diabetes after Normalization of Blood sugar. J. Clin. Invest. 51:1806, 1971. |
21. | Bearumont, P. Schofield, P.J., Hollows, F.C. et al :Growth hormone, Sorbitol and Diabetic Capillary Disease : Lancet 1:579, 1971. |
22. | Albert, K.C.M.M. and Hockaday, T.D.R.: The Biochemistry of the complications of diabetes mellitus In.: Complications of Diabetes edited by H. Keen and J. Jannet. P.P. 22:264. Edward Arnold, London, 1975. |
23. | Sarji, K.E.; Levine, J.W.; Nair, R.M.S. et al.: Relation between Growth Hormone Levels and von-Willebrand Factor Activity, J.Clin. Endo. & Metals. |
[Table - 1], [Table - 2], [Table - 3]
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