Diabetes Mellitus is Frequent, But Retinopathy is Rare in Acromegaly: A Cross-sectional Study
Diabetes and Retinopathy in Acromegaly
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https://doi.org/10.5281/zenodo.10019784Keywords:
Acromegaly, retinopathy, growth hormone, diabetes mellitus, insulin like growth hormoneAbstract
Background: The roles of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in diabetic retinopathy (DR) are well recognized, but the prevalence and pathogenesis of retinopathy in acromegaly are not fully understood. We established the frequency and severity of glucose intolerance and retinopathy—and the relationship between them—in patients with acromegaly.
Methods: All patients with acromegaly under the care of the Department of Endocrinology, Baskent University Hospital were enrolled. Fundoscopy was carried out by two experienced ophthalmologists. Acromegaly disease state was evaluated by basal GH and IGF-1 measurements, and an oral glucose tolerance test (OGTT) when appropriate. Glucose tolerance states were assessed by means of fasting and postprandial plasma glucose concentrations, glycohemoglobin measurement and an OGTT when appropriate. The relationships between retinopathy, acromegaly disease activity and glucose tolerance states were examined.
Results: The cohort comprised 49 patients with acromegaly (24 women), with a median disease duration of 25 months (range 1–420 months). Thirty-three had active disease, with median concentrations of GH of 5.54 ng/ml (0.72–172 ng/ml) and IGF-1 of 541.5 ng/ml (203–1,985 ng/ml). The prevalence of diabetes mellitus (DM) was 30.6% (n =15; 10 patients had active acromegaly, five of whom had uncontrolled DM). Two patients had retinopathy (4.1%); both had active acromegaly and uncontrolled DM at the time of examination.
Conclusions: The prevalence of DM was twice that of a reference population, but that of DR was lower than expected. Our findings suggest that disease activity in acromegaly might not contribute to retinopathy.
References
Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376(9735):124-136. doi:10.1016/S0140-6736(09)62124-3
Aiello LP, Gardner TW, King GL, et al. Diabetic retinopathy. Diabetes Care. 1998;21(1):143-156. doi:10.2337/diacare.21.1.143
Grant MB, Afzal A, Spoerri P, Pan H, Shaw LC, Mames RN. The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs. 2004;13(10):1275-1293. doi:10.1517/13543784.13.10.1275
Meyer-Schwickerath R, Pfeiffer A, Blum WF, et al. Vitreous levels of the insulin-like growth factors I and II, and the insulin-like growth factor binding proteins 2 and 3, increase in neovascular eye disease. Studies in nondiabetic and diabetic subjects. J Clin Invest. 1993;92(6):2620-2625. doi:10.1172/JCI116877
Alzaid AA, Dinneen SF, Melton LJ 3rd, Rizza RA. The role of growth hormone in the development of diabetic retinopathy. Diabetes Care. 1994;17(6):531-534. doi:10.2337/diacare.17.6.531
Chantelau E. Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy. Br J Ophthalmol. 1998;82(7):725-730. doi:10.1136/bjo.82.7.725
Merimee TJ, Zapf J, Froesch ER. Insulin-like growth factors. Studies in diabetics with and without retinopathy. N Engl J Med. 1983;309(9):527-530. doi:10.1056/NEJM198309013090904
Lee HC, Lee KW, Chung CH, et al. IGF-I of serum and vitreous fluid in patients with diabetic proliferative retinopathy. Diabetes Res Clin Pract. 1994;24(2):85-88. doi:10.1016/0168-8227(94)90024-8
Arner P, Sjöberg S, Gjötterberg M, Skottner A. Circulating insulin-like growth factor I in type 1 (insulin-dependent) diabetic patients with retinopathy. Diabetologia. 1989;32(10):753-758. doi:10.1007/BF00274537
Sévin R. The correlation between human growth hormone (HGH) concentration in blood plasma and the evolution of diabetic retinopathy. Ophthalmologica. 1972;165(1):71-77. doi:10.1159/000308471
Melmed S, Kleinberg D. Williams Textbook of Endocrinology. Pituitary Masses and tumors. Philelphia: Elsevier Saunders, 2011:229-290.
Inokuchi N, Ikeda T, Yasuda F, Shirai S, Uchinori Y. Severe proliferative diabetic retinopathy associated with acromegaly. Br J Ophthalmol. 1999;83(5):629-630. doi:10.1136/bjo.83.5.628c
Ballintine EJ, Foxman S, Gorden P, Roth J. Rarity of diabetic retinopathy in patients with acromegaly. Arch Intern Med. 1981;141(12):1625-1627.
Amemiya T, Toibana M, Hashimoto M, Oseko F, Imura H. Diabetic retinopathy in acromegaly. Ophthalmologica. 1978;176(2):74-80. doi:10.1159/000308696
Arya KR, Pathare AV, Chadda M, Menon PS. Diabetes in acromegaly--a study of 34 cases. J Indian Med Assoc. 1997;95(10):546-547.
Tran HA, Petrovsky N, Field AJ. Severe diabetic retinopathy: a rare complication of acromegaly. Intern Med J. 2002;32(1-2):52-54.
Malhotra C. Proliferative diabetic retinopathy in acromegaly. Oman J Ophthalmol. 2010;3(2):96-97. doi:10.4103/0974-620X.64237
Azzoug S, Chentli F. Diabetic retinopathy in acromegaly. Indian J Endocrinol Metab. 2014;18(3):407-409. doi:10.4103/2230-8210.131207
Giustina A, Barkan A, Casanueva FF, et al. Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab. 2000;85(2):526-529. doi:10.1210/jcem.85.2.6363
American Diabetes Association. Standards of medical care in diabetes--2009. Diabetes Care. 2009;32 Suppl 1(Suppl 1):S13-S61. doi:10.2337/dc09-S013
Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677-1682. doi:10.1016/S0161-6420(03)00475-5
Satman I, Omer B, Tutuncu Y, et al. Twelve-year trends in the prevalence and risk factors of diabetes and prediabetes in Turkish adults. Eur J Epidemiol. 2013;28(2):169-180. doi:10.1007/s10654-013-9771-5
PW. Frequency of acromegaly in adults with diabetes or glucose intolerance and estimated prevalence in the general population. Pituitary. 2011;14(3):217-221. doi:10.1007/s11102-010-0281-0
Melmed S. Medical progress: Acromegaly [published correction appears in N Engl J Med. 2007 Feb 22;356(8):879]. N Engl J Med. 2006;355(24):2558-2573. doi:10.1056/NEJMra062453
Biering H, Knappe G, Gerl H, Lochs H. Diabetes-Häufigkeit bei Akromegalie und Cushing-Syndrom [Prevalence of diabetes in acromegaly and Cushing syndrome]. Acta Med Austriaca. 2000;27(1):27-31. doi:10.1046/j.1563-2571.2000.200106.x
Stelmachowska-Banaś M, Zdunowski P, Zgliczyński W. Abnormalities in glucose homeostasis in acromegaly. Does the prevalence of glucose intolerance depend on the level of activity of the disease and the duration of the symptoms?. Endokrynol Pol. 2009;60(1):20-24.
Kreze A, Kreze-Spirova E, Mikulecky M. Risk factors for glucose intolerance in active acromegaly. Braz J Med Biol Res. 2001;34(11):1429-1433. doi:10.1590/s0100-879x2001001100009
Rodrigues TC, Costenaro F, Fedrizzi D, et al. Diabetes mellitus in a cohort of patients with acromegaly. Arq Bras Endocrinol Metabol. 2011;55(9):714-719. doi:10.1590/s0004-27302011000900008
Alexopoulou O, Bex M, Kamenicky P, Mvoula AB, Chanson P, Maiter D. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients. Pituitary. 2014;17(1):81-89. doi:10.1007/s11102-013-0471-7
Fieffe S, Morange I, Petrossians P, et al. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry. Eur J Endocrinol. 2011;164(6):877-884. doi:10.1530/EJE-10-1050
Schneider HJ, Friedrich N, Klotsche J, et al. Prediction of incident diabetes mellitus by baseline IGF1 levels. Eur J Endocrinol. 2011;164(2):223-229. doi:10.1530/EJE-10-0963
Rymaszewski Z, Cohen RM, Chomczynski P. Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro. Proc Natl Acad Sci U S A. 1991;88(2):617-621. doi:10.1073/pnas.88.2.617
Smith LE, Kopchick JJ, Chen W, et al. Essential role of growth hormone in ischemia-induced retinal neovascularization. Science. 1997;276(5319):1706-1709. doi:10.1126/science.276.5319.1706
Hyer SL, Sharp PS, Brooks RA, Burrin JM, Kohner EM. A two-year follow-up study of serum insulinlike growth factor-I in diabetics with retinopathy. Metabolism. 1989;38(6):586-589. doi:10.1016/0026-0495(89)90222-9
Wang Q, Dills DG, Klein R, Klein BE, Moss SE. Does insulin-like growth factor I predict incidence and progression of diabetic retinopathy?. Diabetes. 1995;44(2):161-164. doi:10.2337/diab.44.2.161
Janssen JA, Lamberts SW. Circulating IGF-I and its protective role in the pathogenesis of diabetic angiopathy. Clin Endocrinol (Oxf). 2000;52(1):1-9. doi:10.1046/j.1365-2265.2000.00922.x
Laron Z, Weinberger D. Diabetic retinopathy, nephropathy and cardiovascular disease in a patient with GH gene deletion. Clin Endocrinol (Oxf). 2005;63(6):699-700. doi:10.1111/j.1365-2265.2005.02402.x
Koller EA, Green L, Gertner JM, Bost M, Malozowski SN. Retinal changes mimicking diabetic retinopathy in two nondiabetic, growth hormone-treated patients. J Clin Endocrinol Metab. 1998;83(7):2380-2383. doi:10.1210/jcem.83.7.4953
Wilkinson-Berka JL, Wraight C, Werther G. The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy. Curr Med Chem. 2006;13(27):3307-3317. doi:10.2174/092986706778773086
Sönksen PH, Russell-Jones D, Jones RH. Growth hormone and diabetes mellitus. A review of sixty-three years of medical research and a glimpse into the future?. Horm Res. 1993;40(1-3):68-79. doi:10.1159/000183770
van Setten G, Brismar K, Algvere P. Elevated intraocular levels of insulin-like growth factor I in a diabetic patient with acromegaly. Orbit. 2002;21(2):161-167. doi:10.1076/orbi.21.2.161.7186
Barnes AJ, Kohner EM, Johnston DG, Alberti KG. Severe retinopathy and mild carbohydrate intolerance: possible role of insulin deficiency and elevated circulating growth hormone. Lancet. 1985;1(8444):1465-1468. doi:10.1016/s0140-6736(85)92250-0
Wu TE, Chen HS. Increased prevalence of proliferative retinopathy in patients with acromegaly. J Chin Med Assoc. 2018;81(3):230-235. doi:10.1016/j.jcma.2017.09.013
Wu TE, Chen HS. The role of growth hormone and IGF-1 in retinopathy: a prospective study of retinopathy in patients with acromegaly and impaired fasting glucose. Diabetol Metab Syndr. 2022;14(1):38. Published 2022 Mar 5. doi:10.1186/s13098-022-00806-z
Tas A, Bayraktar MZ, Erdem U, Sobaci G, Ucar M. Prevalence and risk factors for diabetic retinopathy in Turkey. Gulhane Medical Journal. 2005; 47(3):164-174.
Hernández C, Simó R; European Consortium for the Early Treatment of Diabetic Retinopathy (EUROCONDOR). Somatostatin replacement: a new strategy for treating diabetic retinopathy. Curr Med Chem. 2013;20(26):3251-3257. doi:10.2174/09298673113209990024
Grant MB, Caballero S Jr. The potential role of octreotide in the treatment of diabetic retinopathy. Treat Endocrinol. 2005;4(4):199-203. doi:10.2165/00024677-200504040-00001
Yuno A, Ikota A, Koizumi S, et al. Advanced proliferative diabetic retinopathy and macular edema in acromegaly: a case report and literature review. Diabetol Int. 2022;13(3):575-579. Published 2022 Jan 25. doi:10.1007/s13340-022-00571-4
Colao A, Auriemma RS, Galdiero M, et al. Impact of somatostatin analogs versus surgery on glucose metabolism in acromegaly: results of a 5-year observational, open, prospective study. J Clin Endocrinol Metab. 2009;94(2):528-537. doi:10.1210/jc.2008-1546
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