Serum high sensitivity C reactive protein levels in patients with diabetic retinopathy: a cross sectional study
Keywords:Diabetes, Fundus, Glycemic control, Kanski's system, Proliferative
Background: Diabetic retinopathy (DR) is one of the major visual morbidities associated with diabetes. This study determined the levels of serum high-sensitivity C-reactive protein (hs-CRP) in patients with DR and to correlate the estimated levels of serum hs-CRP with the severity of DR and other coexisting factors.
Methods: This was a cross-sectional study conducted between March 2009 and August 2010 and included patients with type 2 diabetes mellitus (T2DM) with or without DR. A detailed fundus evaluation was performed using direct and indirect ophthalmoscopy. The retinopathies were observed and documented in accordance with the Kanski's system of classification as background DR (BDR), pre-proliferative DR (PPDR), and proliferative DR (PDR). Laboratory investigations determined the levels of fasting blood glucose (FBG), postprandial blood glucose (PPBG), glycosylated hemoglobin, urine albumin excretion, and serum hs-CRP levels.
Results: In total, 80 patients with T2DM were included (DR group, n=40 [BDR, n=22; PDR, n=11; PPDR, n=7]; control group, n=40). Highest serum hs-CRP levels were found in PDR group (6.68 mg/L), followed by PPDR and BDR group (3.2 mg/L and 1.56 mg/L, respectively). The PDR group showed the longest duration of diabetes (16 years), highest FBG (221.8 mg/dL) and HbA1c (6.68 mg/L). The incidence of albuminuria and maculopathy was higher in PDR group (72.7% and 54.54%, respectively). A significant association of hs-CRP levels with DR in patients with T2DM was observed. A significantly (<0.005) positive correlation of hs-CRP was also observed with age, duration of disease, FBG, PPBG, and HbA1c.Conclusions: Patients with severe grades of retinopathy had significantly higher hs-CRP levels than patients with the milder grades.
Targher G, Bertolini L, Zenari L, Lippi G, Pichiri I, Zoppini G, et al. Diabetic retinopathy is associated with an increased incidence of cardiovascular events in Type 2 diabetic patients. Diabet Med. 2008; 25:45-50.
Holekamp N. Overview of diabetic macular edema. Am J Manag Care. 2016;22:S284-91.
Prevalence of diabetic retinopathy in India is 16.9%: Survey. Available at: https://www.aninews.in/news/health/prevalence-of-diabetic-retinopathy-in-india-is-169-survey20191010175050/. Accessed 26th December 2019.
Vainas T, Stassen F, Graff R, Twiss E, Herngreen S, Welton R, et al. C-reactive protein in peripheral arterial disease: relation to severity of the disease and to future cardiovascular events. J Vasc Surg. 2005;42:243-51.
Navarro J, Mora C. Role of inflammation in diabetic complications. Nephrol Dial Transplant. 2005;20: 2601-4.
Arar NH, Freedman BI, Adler SG, Iyengar SK, Chew EY, Davis MD, et al. Heritability of the severity of diabetic retinopathy: the FIND-Eye study. Invest Ophthalmol Vis Sci. 2008;49:3839-45.
Ng DP. Human genetics of diabetic retinopathy: current perspectives. J Ophthalmol. 2010; 2010:172593.
Heng LZ, Comyn O, Peto T, Tadros C, Ng E, Sivaprasad S, et al. Diabetic retinopathy: pathogenesis, clinical grading, management and future developments. Diabet Med. 2013;30:640-50.
Rangasamy S, McGuire PG, Das A. Diabetic retinopathy and inflammation: novel therapeutic targets. Middle East Afr J Ophthalmol. 2012;19:52-9.
Peng D, Wang J, Zhang R, Tang S, Jiang F, Chen M, et al. C-reactive protein genetic variant is associated with diabetic retinopathy in Chinese patients with type 2 diabetes. BMC Endocr Disord. 2015; 2(15):8.
Hayashino Y, Mashitani T, Tsujii S, Ishii H, Diabetes Distress and Care Registry at Tenri Study Group. Serum high-sensitivity C-reactive protein levels are associated with high risk of development, not progression, of diabetic nephropathy among Japanese type 2 diabetic patients: a prospective cohort study (Diabetes Distress and Care Registry at Tenri [DDCRT7]). Diabetes Care. 2014;37:2947-52.
Tsunoda K, Arita M, Yukawa M, Ueyama M, Furuta M, Nakagawa T, et al. Retinopathy and hypertension affect serum high-sensitivity C-reactive protein levels in type 2 diabetic patients. J Diabetes Complica. 2005;19:123-7.
Gopinath G, Kakkanatt V, Bisto AA, Mathai MT. Correlation of C-reactive protein and glycosylated hemoglobin on severity of diabetic macular edema. Kerala J Ophthalmol. 2019;31:131-7.
Song J, Chen S, Liu X, Duan H, Kong J, Li Z. Relationship between C-Reactive protein level and diabetic retinopathy: a systematic review and meta-analysis. PLoS ONE. 2015;10:e0144406.
Chen YS. Contents changes and correlations between homocysteine and cystatin C in patients with diabetic retinopathy in type 2 diabetes mellitus. Int J Ophthalmol. 2010;10:2107-10.
Jia ZT, Liu CY, Li H. Changes of the concentration of serum ischemia modified albumin and high sensitivity C-reactive protein in type 2 diabetic patients with retinopathy]. Zhonghua Yan Ke Za Zhi. 2009;45:805-8.
Pepys MB, Hirschfield GM. C‐reactive protein: a critical update. J Clin Invest. 2003;111:1805-12.
Fong DS, Aiello LP, Ferris FL Klein R. Diabetic retinopathy. Diabetes Care. 2004;27:2540‑53.
Bertin E, Nguyen P, Guenounou M, Durlach V, Potron G, Leutenegger M. Plasma levels of tumor necrosis factor-alpha (TNF-alpha) are essentially dependent on visceral fat amount in type 2 diabetic patients. Diabetes Metab. 2000;26:178-82.
Engelsen D, Koekkoek P, Gorter K, Donk M, Salome P, Rutten G. High-sensitivity C-reactive protein to detect metabolic syndrome in a centrally obese population: a cross-sectional analysis. Cardiovasc Diabetol. 2012;11:25.
Chuengsamarn S, Rattanamongkolgul S, Sittithumcharee G, Jirawatnotai S. Association of serum high-sensitivity C-reactive protein with metabolic control and diabetic chronic vascular complications in patients with type 2 diabetes. Diabetes Metab Syndr. 2017;11:103-8.
Rani PK, Raman R, Gupta A, Pal SS, Kulothungan V, Sharma T. Albuminuria and diabetic retinopathy in type 2 diabetes mellitus Sankara Nethralaya diabetic retinopathy epidemiology and molecular genetic study (SN-DREAMS, report 12). Diabetol Metab Syndr. 2011;3:9.
Boelter MC, Gross JL, Canani LH, Costa LA, Lisboa HR, Três GS, et al. Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes. Braz J Med Biol Res. 2006;39:1033-9.
Ra H, Yoo JH, Ban WH, Song HC, Lee SS, Kim SR, et al. Predictors for diabetic retinopathy in normoalbuminuric people with type 2 diabetes mellitus. Diabetol Metab Syndr. 2012;4:29.
Zander E, Herfurth S, Bohl B, Heinke P, Herrmann U, Kohnert K, et al. Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors. B J Ophthalmol. 2000;84:871-6.
Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med. 2007;24:137-44.
Tomić M, Ljubić S, Kaštelan S, Gverović Antunica A, Jazbec A, Poljičanin T. Inflammation, haemostatic disturbance, and obesity: possible link to pathogenesis of diabetic retinopathy in type 2 diabetes. Mediators Inflamm. 2013;2013:818671.
Blum A, Socea D, Ben-Shushan RS, Keinan-Boker L, Naftali M, Segol G, et al. A decrease in VEGF and inflammatory markers is associated with diabetic proliferative retinopathy. Eur Cytokine Netw. 2012;23:158-62.