ASSOCIATION OF SERUM TOTAL BILIRUBIN LEVEL WITH DIABETIC RETINOPATHY IN TYPE 2 DIABETES MELLITUS
AbstractBackground: Serum bilirubin has anti-inflammatory, antioxidant and immunological properties. It is considered a protective substance against atherosclerotic and microvascular complications of diabetes mellitus (DM). This study was designed to find the association between total serum bilirubin concentration and diabetic retinopathy (DR). Methods: This case control study was conducted in the Department of Endocrinology, Diabetes and Metabolic Diseases, Hayatabad Medical Complex, Peshawar. Type-2 DM patients more than 18 years of age of either gender with duration of T2DM more than 6 months were included and sub categorized in two groups. Cases (DM with DR) and Controls (DM without DR) while patients with acute and chronic liver diseases, haemolytic anaemia, history of chronic alcohol consumption, use of hepatotoxic drugs (anti-tuberculous, anti-epileptic), women on oral contraceptive pills were excluded. All participants underwent ophthalmic examination at diabetic retinopathy screening clinic followed by pre designed set of investigations. Results: A total of 152 patients, 76 cases and 76 controls were included. Serum bilirubin concentration was found inversely and independently (p 0.000) associated and inversely co related (r -0.345and p 0.000) with prevalence of DR. Cases were concentrated in the lower quartiles of serum bilirubin concentration and vice versa. Low haemoglobin (p 0.00) and longer duration of DM (0.003) were independently and directly associated with prevalence of DR. Conclusion: Serum bilirubin concentration is inversely and independently associated and inversely correlated with the prevalence of DR and may predict progression of DR over time. Keywords: Serum bilirubin; Diabetic retinopathy; Diabetes mellitus
Annual Report 2014. International Diabetes Federation [Internet]. [cited 2014 Dec 30]. Available from: http://www.idf.org/annual-report-2014
Basit A, Williams R. Promoting care in underserved communities: launching World Diabetes Day in Karachi. Diabetes Voice 2006;51(2):46–7.
Diabetes Statistics in Pakistan: ABC-of-Diabetes [Internet]. [cited 2014 Dec 30]. Available from: http://diabetespakistan.com/treatment/ABC-of-Diabetes/2013/10/05/diabetes-statistics-in-pakistan/
Shera AS, Rafique G, Khuwaja IA, Baqai S, Khan IA, King H. Pakistan National Diabetes Survey. Prevalence of glucose intolerance and associated factors in North West Frontier Province (NWFP) of Pakistan. J Pak Med Assoc 1999;49(9):206–11.
Shera AS, Rafique G, Khuwaja IA, Baqai S, King H. Pakistan National Diabetes Survey. Prevalence of glucose intolerance and associated factors in Baluchistan province. Diabetes Res Clin Pract 1999;44(1):49–58.
Frier BM, Fisher M. Diabetes Mellitus. In: College NR, Walker BR, Ralston SH, editors. Davidson’s Principles and Practice of Medicine. New Delhi: Elsevier; 2010. p.798.
BuseJB, Ginsberg HN, Bakris GL, Clark NG, Costa F, Eckel R, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007;30(1):162–72.
Marozas LM, Fort PE. Diabetic retinopathy-update on prevention techniques, present therapies, and new leads. US Ophthalmic Rev 2014;7(1):54–8.
Sivaprasad S, Gupta B, Crosby-Nwaobi R, Evans J. Prevalence of diabetic retinopathy in various ethnic groups: A Worldwide Perspective. Surv Ophthalmol 2012;57(4):347–70.
Rema M, Premkumar S, Anitha B, Deepa R, Pradeepa R, Mohan V. Prevalence of diabetic retinopathy in urban India: the Chennai Urban Rural Epidemiology Study (CURES) Eye Study, I. Invest Ophthalmol Vis Sci 2005;46(7):2328–33.
Wong TY, Klein R, Islam FM, Cotch MF, Folsom AR, Klein BE, et al. Diabetic retinopathy in a multi-ethnic cohort in the United States. Am J Ophthalmol 2006;141(3):446–55.
Diabetic Retinopathy - Asia Pacific - American Academy of Ophthalmology [Internet]. [cited 2014 Sep 21]. Available from: http://www.aao.org/topic-detail/diabetic-retinopathy--asia-pacific
Han SS, Na KY, Chae DW, Kim YS, Chin HJ. High serum bilirubin is associated with reduced risk of Diabetes Mellitus and Diabetic Nephropathy. Tohoku J Exp Med 2010;221(2):133–40.
Inoguchi T, Sasaki S, Kobayashi K, Takayanagi R, Yamada T. Relationship between Gilbert syndrome and prevalence of vascular complications in patients with diabetes. JAMA 2007;298(12):1398–400.
Mashitani T, Hayashino Y, Okamura S, Tsujii S, Ishii H. Correlations between serum bilirubin levels and diabetic nephropathy progression among Japanese type 2 diabetic patients: a prospective cohort study (diabetes distress and care registry at tenri [DDCRT 5]). Diabetes Care 2014;37(1):252–8.
Fukui M, Tanaka M, Yamazaki M, Hasegawa G, Nishimura M, Iwamoto N, et al. Low serum bilirubin concentration in haemodialysis patients with Type 2 diabetes. Diabet Med 2011;28(1):96–9.
Yasuda M, Kiyohara Y, Wang JJ, Arakawa S, Yonemoto K, Doi Y, et al. High serum bilirubin levels and diabetic retinopathy: the Hisayama Study. Ophthalmology 2011;118(7):1423–8.
Shuji S, Toyoshi T. Role of Oxidative stress in pathogenesis of diabetic vascular complications. Diabetes Metab J 2012;36(4):255–61.
Vítek L, Malíková I, Kvasnicka J, Benáková H, Novotný L. Relationship between serumbilirubin and markers of inflammation and oxidative stress. J Gastroenterol Hepatol 2007;22:235.
Bernhard K, Ritzel G, Steiner K. Über eine biologische Bedeutung der Gallenfarbstoffe. Bilirubin und Biliverdin als Antioxydantien für das Vitamin A und die essentiellen Fettsäuren. Helv Chim Acta 1954;37(1):306–13.
Wu TW, Fung KP, Yang CC. Unconjugated bilirubin inhibits the oxidation of human low density lipoprotein better than Trolox. Life Sci 1994;54(25):477–81.
Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KP, Snyder SH. Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proc Natl Acad Sci U S A 2009;106(13):5171–6.
Mazzone GL, Rigato I, Ostrow JD, Bossi F, Bortoluzzi A, Sukowati CH, et al. Bilirubin inhibit the TNFalpha-related induction of three endothelial adhesion molecules. Biochem Biophys Res Commun 2009;386(2):338–44.
Rocuts F, Zhang X, Yan J, Yue Y, Thomas M, Bach FH, et al. Bilirubin promotes de novo generation of T regulatory cells. Cell Transplant 2010;19(4):443–51.
Cho HC. The relationship among homocysteine, bilirubin, and diabetic retinopathy. Diabetes Metab J 2011;35(6):595–601.
Najam SS, Sun J, Zhang J, Xu M, Lu J, Sun K, et al. Serum total bilirubin levels and prevalence of diabetic retinopathy in a Chinese population. J Diabetes 2014;6(3):221–7.
Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic Study of Diabetic Retinopathy II. Prevalence and Risk of Diabetic Retinopathy When Age at Diagnosis is Less Than 30 Years. Arch Ophthalmol 1984;102(4):520–26.
Qiao Q, Keinänen-Kiukaanniemi S, Läärä E. Relationship between hemoglobin levels and diabetic retinopathy. J Clin Epidemiol 1997;50(2):153–8.
Dave A, Kalra P, Gowda BHR, Krishnaswamy M, Association of Bilirubin and Malondiaaldehyde levels with retinopathy in type 2 Diabetes Mellitus. Indian J Endocrinol Metab 2015;19(3):373–7.
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.