Association between retinol binding protein 4 and diabetic retinopathy among type 2 diabetic patients: a meta-analysis.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Diabetes Mellitus, Type 2/*blood ; Diabetic Retinopathy/*blood ; Diabetic Retinopathy/*diagnosis ; Retinol-Binding Proteins, Plasma/*metabolism; Biomarkers/analysis ; Biomarkers/blood ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Diabetic Retinopathy/epidemiology ; Diabetic Retinopathy/pathology ; Disease Progression ; Female ; Humans ; Observational Studies as Topic/statistics & numerical data ; Retinol-Binding Proteins, Plasma/analysis

Aims: The aim of this study was to investigate the association between retinol-binding protein 4 (RBP4) and diabetic retinopathy (DR) among patients with type 2 diabetes mellitus (T2DM).
Methods: Databases PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure, VIP, and Wangfang were searched to July 30, 2019. The Newcastle-Ottawa Scale was applied to assess the quality of all identified studies, and those qualified were included in the meta-analysis. The Chi squared Q test and I ² statistics were conducted to evaluate heterogeneity. Standardized mean differences (SMD) and 95% confidence intervals (CI) among RBP4 within the DR and T2DM without retinopathy (DWR) groups were pooled using the random effects model depending on the heterogeneity. Subgroup analyses were conducted among the groups having different diabetes duration, detection methods, body mass index, and total cholesterol and triglyceride levels. The funnel plot was used to assess publication bias.
Results: Nineteen observational studies were included in our meta-analysis. RBP4 was significantly higher in both nonproliferative DR (SMD: 0.72, 95% CI 0.48-0.95, P < 0.00001) and proliferative DR (SMD: 2.68, 95% CI 1.69-3.67, P < 0.00001) groups despite high heterogeneity (I ²  = 87 and 97% in DR and PDR groups, respectively). Significant differences were noted among most subgroups (P < 0.05). Among those accompanied by hypercholesterolemia, the association between RBP4 and DR were unclear (P = 0.09).
Conclusions: Elevated RBP4 is strongly associated with DR and may play an essential role in its progression. Additional large-scale controlled studies are needed to confirm these findings.

Cheung N, Mitchell P, Wong TY (2010) Diabetic retinopathy. Lancet 376(9735):244–252.
Whiting DR, Guariguata L, Weil L, Shaw J (2011) IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract 94(3):311–321. (PMID: 22079683)
Ting DS, Cheung GC, Wong TY (2016) Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol 44(4):260–277. (PMID: 26716602)
Antonetti DA, Barber AJ, Bronson SK, Freeman WM, Gardner TW, Jefferson LS et al (2006) Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes 55(9):2401–2411. (PMID: 16936187)
Curtis TM, Gardiner TA, Stitt AW (2009) Microvascular lesions of diabetic retinopathy: Clues towards understanding pathogenesis? Eye 23(7):1496–1508. (PMID: 19444297)
Dong J, Wong TY (2012) Current epidemiology of diabetic retinopathy and diabetic macular edema. Curr Diab Rep 12(4):346–354.
Kappelgaard P, Holfort SK, Klefter ON, Larsen M (2018) Retinal vessel diameter changes in relation to dark adaptation and acute hyperglycemia. J Ophthalmol 2018:7064359. (PMID: 303198196167562)
Afrashi F, Erakgün T, Köse S, Ardiç K, Menteş J (2003) Blue-on-yellow perimetry versus achromatic perimetry in type 1 diabetes patients without retinopathy. Diabetes Res Clin Pract 61(1):7–11. (PMID: 12849918)
Wolff BE, Bearse MA, Schneck ME, Dhamdhere K, Harrison WW, Barez S et al (2015) Color vision and neuroretinal function in diabetes. Doc Ophthalmol 130(2):131–139. (PMID: 25516428)
Tawfik A, Mohamed R, Elsherbiny NM, DeAngelis MM, Bartoli M, Al-Shabrawey M (2019) Homocysteine: a potential biomarker for diabetic retinopathy. J Clin Med 8(1):E121. (PMID: 30669482)
Malecki MT, Undas A, Cyganek K, Mirkiewicz-Sieradzka B, Wolkow P, Osmenda G et al (2007) Plasma asymmetric dimethylarginine (ADMA) is associated with retinopathy in type 2 diabetes. Diabetes Care 30(11):2899–2901. (PMID: 17704346)
Reddy VS, Sethi S, Agrawal P, Gupta N, Garg R (2015) Ischemia modified albumin (IMA) and albumin adjusted-IMA (AAIMA) as biomarkers for diabetic retinopathy. Nepal J Ophthalmol 7(14):117–123. (PMID: 27363956)
Rodríguez AJ, Nunes Vdos S, Mastronardi CA, Neeman T, Paz-Filho GJ (2016) Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of controlled cross-sectional studies. J Diabetes Complicat 30(2):357–367. (PMID: 26684169)
Chen H, Zhang X, Liao N, Wen F (2016) Increased levels of IL-6, sIL-6R, and sgp130 in the aqueous humor and serum of patients with diabetic retinopathy. Mol Vis 22:1005–1014. (PMID: 275632324978206)
Palanisamy K, Raman R, Sulochana KN, Chidambaram S (2019) Adiponectin: a potential candidate for treating fibrosis in posterior segment of the eye. Med Hypotheses 123:9–12. (PMID: 30696604)
Majerczyk M, Kocełak P, Choręza P, Arabzada H, Owczarek AJ, Bożentowicz-Wikarek M et al (2018) Components of metabolic syndrome in relation to plasma levels of retinol binding protein 4 (RBP4) in a cohort of people aged 65 years and older. J Endocrinol Invest 41(10):1211–1219. (PMID: 295241776182353)
Borodkina DA, Gruzdeva OV, Belik EV, Palicheva EI, Kuzmina AA (2018) The perspectives of application of retinol-binding protein as a biomarker of risk of cardiovascular pathology. Klin Lab Diagn 63(2):79–84. (PMID: 30672670)
Quadro L, Blaner WS, Salchow DJ, Vogel S, Piantedosi R, Gouras P et al (1999) Impaired retinal function and vitamin A availability in mice lacking retinolbinding protein. EBO J 18(17):4633–4644.
Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM et al (2005) Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 436(7049):356–362. (PMID: 16034410)
Li ZZ, Lu XZ, Liu JB, Chen L (2010) Serum retinol-binding protein 4 levels in patients with diabetic retinopathy. J Int Med Res 38(1):95–99. (PMID: 20233518)
Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T (2007) Retinol binding protein-4 levels and clinical features of type 2 diabetes patients. J Clin Endocrinol Metab 92(7):2712–2719. (PMID: 17440021)
Li JY, Chen XX, Lu XH, Zhang CB, Shi QP, Feng L (2018) Elevated RBP4 plasma levels were associated with diabetic retinopathy in type 2 diabetes. Biosci Rep 38(5):BSR20181100. (PMID: 301351386131341)
Stang A (2010) Critical evaluation of the Newcastle–Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. (PMID: 2065237020652370)
Zhao L, Wu C, Zhao J (2016) Change of serum RBP4 level in patients with diabetic retinopathy combined with subclinical hypothyroidism and its influence on diabetic retinopathy. Chin Gen Pract 19(8):903–907 (Chinese).
Zhao LJ, Wang W (2013) Association of serum retinol binding protein 4 with diabetic retinopathy in type 2 diabetes mellitus. J Southeast Univ (Med Sci Ed) 32(3):266–269 (Chinese).
Gao Y, Huang Q, Liu LT, Wang YQ (2015) Correlation between retinol binding protein 4 and type 2 diabetic retinopathy. Zhejiang Jo Integr Tradit Chinese West Med 25(5):489–490 (Chinese).
Tian T, Ma XH, Shen J (2011) Association of serum lipoprotein (a) level, retinol-binding protein 4 with diabetic retinopathy in type 2 diabetes. Acta Univ Med Nanjing (Nat Scie) 31(11):1620–1622+1652 (Chinese).
Liang D (2012) Study on factors influencing type 2 diabetic retinopathy. Hebei Medical University, Shijiazhuang (Chinese).
Jiang FS (2009) The meaning of serum retinal binding protein 4 in studying diabetic retinopathy in type 2 diabetes. Suzhou Univ J Med Sci (Chinese).
Yin Q, Guo SQ, Zhang YL, Wang H, Xiao YX, Wang J et al (2016) Relationship of serum RBP4 and neutrophil- lymphocyte ratio with type 2 diabetic retinopathy. Chin J Mod Med 26(6):54–58 (Chinese).
Jiang F, Li YM, Deng B, Chen LL (2013) The correlation between diabetic retinopathy and serum retinol binding protein 4 in type 2 diabetes. J Trop Med 13(9):1075–1077, 1094 (Chinese).
Wang LJ, Wang DQ, Zhou YH, Han XJ, Yuan XL, Qian J (2018) Changes and significance of serum retinol binding protein 4 and cystatin C levels in patients with diabetic retinopathy. Chin Gen Pract 21(5):517–520, 525 (Chinese).
Wang XJ (2018) The relationship between serum retinol binding protein 4 and diabetic retinopathy in type 2 diabetes. Guangxi Medical University, Nanning (Chinese).
Li PW (2018) Clinical study on the relationship between serum retinol binding protein 4 and type 2 diabetic retinopathy. Zhengzhou University, Zhengzhou (Chinese).
Bao T, Pan HF, Qi Y, Hao L (2018) Value of combined detection of serum markers in early diabetic retinopathy using ROC curve. Contemp Med 24(29):38–41 (Chinese).
Huang LL, Yu J, Zhou SX, Wang L, Peng Y, Liu XL et al (2016) Correlation analysis of Hcy and RBP4 with diabetic retinopathy. Rec Adv Ophthal 36(3):244–246 (Chinese).
Zhou HY, Yue XL, Shi JH (2013) The correlative study of serum retinol-binding protein 4 and diabetic retinopathy of elderly type 2 diabetic patient. J Bengbu Med Coll 7(38):803–808 (Chinese).
Yao JP, Li SB, Zheng SY, Qiu W (2015) Relationship between serum retinol binding protein 4 and diabetic retinopathy. Zhejiang Med J 37(12):1058–1060 (Chinese).
Xu SH, Liu J, Yang XT, Jing L, Lin SD, Wu D et al (2017) Correlation between type 2 diabetic retinopathy and serum retinol 4 levels. Diabetes New Word 20(18):161–162 (Chinese).
Zheng Y, He M, Congdon N (2012) The worldwide epidemic of diabetic retinopathy. Indian J Ophthalmol 60(5):428–431. (PMID: 229447543491270)
Sasongko MB, Wardhana FS, Febryanto GA, Agni AN, Supanji S, Indrayanti SR (2020) The estimated healthcare cost of diabetic retinopathy in Indonesia and its projection for 2025. Br J Ophthalmol 104:487–492. (PMID: 31285276)
Kern TS (2007) Contributions of inlammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007(2007):95103. (PMID: 182746062216058)
Tang J, Kern TS (2011) Inflammation in diabetic retinopathy. Prog Retin Eye Res 30(5):343–358. (PMID: 2163596421635964)
Nalini M, Raghavulu BV, Annapurna A, Avinash P, Chandi V, Swathi N et al (2017) Correlation of various serum biomarkers with the severity of diabetic retinopathy. Diabetes Metab Syndr 11:S451–S454. (PMID: 28420575)
Akbay E, Muslu N, Nayir E, Ozhan O, Kiykim A (2010) Serum retinol binding protein 4 level is related with renal functions in Type 2 diabetes. J Endocrinol Invest 33(10):725–729. (PMID: 20436266)
Malechka VV, Moiseyev G, Takahashi Y, Shin Y, Ma JX (2017) Impaired rhodopsin generation in the rat model of diabetic retinopathy. Am J Pathol 187(10):2222–2231. (PMID: 287349465809515)
Racz B, Petrukhin K (2017) Effect of the advanced non-retinoid RBP4 antagonist on vascular permeability in the mouse diabetic retinopathy model. Investig Ophthalmol Vis Sci 58(8):5799.
Farjo KM, Farjo RA, Halsey S, Moiseyev G, Ma JX (2012) Retinol-binding protein 4 induces inflammation in human endothelial cells by an NADPH oxidase- and nuclear factor kappa B-dependent and retinol-independent mechanism. Mol Cell Biol 32(24):5103–5115. (PMID: 230710933510526)
Moraes-Vieira PM, Yore MM, Dwyer PM, Syed I, Aryal P, Kahn BB (2014) RBP4 activates antigen-presenting cells, leading to adipose tissue inflammation and systemic insulin resistance. Cell Metab 19(3):512–526. (PMID: 246069044078000)
Hummasti S, Hotamisligil GS (2010) Endoplasmic reticulum stress and inflammation in obesity and diabetes. Circ Res 107(5):579–591. (PMID: 20814028)
Wei Y, Xia N, Zhang W, Huang J, Ren Z, Zhu L et al (2019) Serum retinol-binding protein 4 is associated with insulin resistance in patients with early and untreated rheumatoid arthritis. Joint Bone Spine 86(3):335–341. (PMID: 30025962)
Soprano DR, Soprano KJ, Goodman DS (1986) Retinol-binding protein messenger RNA levels in the liver and in extrahepatic tissues of the rat. J Lipid Res 27(2):166–171. (PMID: 3754273)
Park SE, Kim DH, Lee JH, Park JS, Kang ES, Ahn CW et al (2009) Retinol-binding protein-4 is associated with endothelial dysfunction in adults with newly diagnosed type 2 diabetes mellitus. Atherosclerosis 204(1):23–25. (PMID: 18838136)
Du M, Martin A, Hays F, Johnson J, Farjo RA, Farjo KM (2017) Serum retinol-binding protein-induced endothelial inflammation is mediated through the activation of toll-like receptor 4. Mol Vis 23(2):185–197. (PMID: 284007005373036)
Du M, Otalora L, Martin AA, Moiseyev G, Vanlandingham P, Wang Q et al (2015) Transgenic mice overexpressing serum retinol-binding protein develop progressive retinal degeneration through a retinoid-independent mechanism. Mol Cell Biol 35(16):2771–2789. (PMID: 260553274508322)
Rostamkhani H, Mellati AA, Tabaei BS, Alavi M, Mousavi SN (2019) Association of serum zinc and vitamin a levels with severity of retinopathy in type 2 diabetic patients: a cross-sectional study. Biol Trace Elem Res 92(2):123–128.
Zhang C, Li K, Zhang J, Kuang X, Liu C, Deng Q et al (2019) Relationship between retinol and risk of diabetic retinopathy: a case-control study. Asia Pac J Clin Nutr 28(3):607–613. (PMID: 31464408)
Voigt M, Schmidt S, Lehmann T, Köhler B, Kloos C, Voigt UA et al (2018) Prevalence and progression rate of diabetic retinopathy in type 2 diabetes patients in correlation with the duration of diabetes. Exp Clin Endocrinol Diabetes 126(9):570–576. (PMID: 29183104)
Qi Q, Yu Z, Ye X, Zhao F, Huang P, Hu FB et al (2007) Elevated retinol-binding protein 4 levels are associated with metabolic syndrome in Chinese people. J Clin Endocrinol Metab 92(12):4827–4834. (PMID: 17878249)
Wang W, Li N (2015) Correlation of retinol binding protein 4 with metabolic indexes of glucose and lipid, bile cholesterol saturation index. Zhong Nan Da Xue Xue Bao Yi Xue Ban 40(6):657–665 (Chinese). (PMID: 26164516)
Hu S, Liu Q, Huang X, Tan H (2016) Serum level and polymorphisms of retinol-binding protein-4 and risk for gestational diabetes mellitus: a meta-analysis. BMC Pregnancy Childbirth 16(1):1–11.
Zhu YY, Zhang JL, Liu L, Han Y, Ge X, Zhao S (2018) Evaluation of serum retinol-binding protein-4 levels as a biomarker of poor short-term prognosis in ischemic stroke. Biosci Rep 38(5):1–11.
Tu WJ, Zeng XW, Deng A, Zhao SJ, Luo DZ, Ma GZ et al (2017) Circulating FABP4 (fatty acid-binding protein 4) Is a novel prognostic biomarker in patients with acute ischemic Stroke. Stroke 48(6):1531–1538. (PMID: 28487339)
Toruner F, Altinova AE, Akturk M, Kaya M, Arslan E, Bukan N et al (2011) The relationship between adipocyte fatty acid binding protein-4, retinol binding protein-4 levels and early diabetic nephropathy in patients with type 2 diabetes. Diabetes Res Clin Pract 91(2):203–207. (PMID: 21176857)

2018YFC1314900 National Key R&D Program of China; 2018YFC1314902 National Key R&D Program of China; 201910304108Y Jiangsu Students' Platform for innovation and entrepreneurship training program; KYCX19_2070 Jiangsu postgraduate research and innovation program

Keywords: Diabetes retinopathy; Proliferative diabetic retinopathy; Retinol-binding protein 4; Type 2 diabetes mellitus

0 (Biomarkers)
0 (RBP4 protein, human)
0 (Retinol-Binding Proteins, Plasma)

Date Created: 20200515 Date Completed: 20201119 Latest Revision: 20210628

20231215

10.1007/s00592-020-01535-3

32405713