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Effects of intensive glycemic control in ocular complications in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

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Abstract

Whether intensive glycemic control can reduce incidence of diabetic retinopathy or other diabetes-associated ocular complications remains undefined. In this meta-analysis, we assessed the effects of intensive versus conventional glycemic control in ocular complications in patients with type 2 diabetes. A systematic literature search of PubMed, Web of Knowledge, and Scopus (until December 12, 2013) was conducted. Randomized controlled trials which compared intensive glycemic control with conventional glycemic control in ocular events in patients with type 2 diabetes were included. Random-effects models were used to measure the pooled odds ratio (OR) with 95 % confidence interval (CI). Seven trials involving 32,523 patients were included. Intensive glycemic control reduced the risks of retinal photocoagulation or vitrectomy (OR 0.86; 95 % CI 0.75–0.98), macular edema (OR 0.65; 95 % CI 0.43–0.99), and progression of retinopathy (OR 0.69; 95 % CI 0.55–0.87). No significant risk reduction was shown in incidence of retinopathy (OR 0.67; 95 % CI 0.26–1.73), cataract surgery (OR 0.88; 95 % CI 0.76–1.03), or severe loss of vision or blindness (OR 0.99; 95 % CI 0.86–1.13). Intensive glycemic control reduces the risk of most retinopathy-related events. But no beneficial effect was shown in ocular endpoint as severe loss of vision or blindness.

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References

  1. B.E. Klein, Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic. Epidemiol. 14, 179–183 (2007)

    Article  PubMed  Google Scholar 

  2. D.A. Antonetti, R. Klein, T.W. Gardner, Diabetic retinopathy. N. Engl. J. Med. 366, 1227–1239 (2012)

    Article  CAS  PubMed  Google Scholar 

  3. J.W. Yau, S.L. Rogers, R. Kawasaki, E.L. Lamoureux, J.W. Kowalski, T. Bek, S.J. Chen, J.M. Dekker, A. Fletcher, J. Grauslund, S. Haffner, R.F. Hamman, M.K. Ikram, T. Kayama, B.E. Klein, R. Klein, S. Krishnaiah, K. Mayurasakorn, J.P. O’Hare, T.J. Orchard, M. Porta, M. Rema, M.S. Roy, T. Sharma, J. Shaw, H. Taylor, J.M. Tielsch, R. Varma, J.J. Wang, N. Wang, S. West, L. Xu, M. Yasuda, X. Zhang, P. Mitchell, T.Y. Wong, Meta-Analysis for Eye Disease (META-EYE) Study Group, Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 35, 556–564 (2012)

    Article  PubMed Central  PubMed  Google Scholar 

  4. E.L. Lamoureux, T.Y. Wong, Diabetic retinopathy in 2011: further insights from new epidemiological studies and clinical trials. Diabetes Care 34, 1066–1067 (2011)

    Article  PubMed Central  PubMed  Google Scholar 

  5. Y.J. Cheng, E.W. Gregg, L.S. Geiss, G. Imperatore, D.E. Williams, X. Zhang, A.L. Albright, C.C. Cowie, R. Klein, J.B. Saaddine, Association of A1C and fasting plasma glucose levels with diabetic retinopathy prevalence in the U.S. population Implications for diabetes diagnostic thresholds. Diabetes Care 32, 2027–2032 (2009)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. H.T. Nguyen, S.D. Luzio, J. Dolben, J. West, L. Beck, P.A. Coates, D.R. Owens, Dominant risk factors for retinopathy at clinical diagnosis in patients with type II diabetes mellitus. J. Diabetes Complications 10, 211–219 (1996)

    Article  CAS  PubMed  Google Scholar 

  7. R. Klein, B.E. Klein, S.E. Moss, K.J. Cruickshanks, Relationship of hyperglycemia to the long-term incidence and progression of diabetic retinopathy. Arch. Intern. Med. 154, 2169–2178 (1994)

    Article  CAS  PubMed  Google Scholar 

  8. T. Shiraiwa, H. Kaneto, T. Miyatsuka, K. Kato, K. Yamamoto, A. Kawashima, T. Kanda, M. Suzuki, E. Imano, M. Matsuhisa, M. Hori, Y. Yamasaki, Postprandial hyperglycemia is a better predictor of the progression of diabetic retinopathy than HbA1c in Japanese type 2 diabetic patients. Diabetes Care 28, 2806–2807 (2005)

    Article  PubMed  Google Scholar 

  9. X.W. Xie, L. Xu, Y.X. Wang, J.B. Jonas, Prevalence and associated factors of diabetic retinopathy. The Beijing Eye Study 2006. Graefes. Arch. Clin. Exp. Ophthalmol. 246, 1519–1526 (2008)

    Article  PubMed  Google Scholar 

  10. M.S. Roy, M. Affouf, Six-year progression of retinopathy and associated risk factors in African American patients with type 1 diabetes mellitus: the New Jersey 725. Arch. Ophthalmol. 124, 1297–1306 (2006)

    Article  PubMed  Google Scholar 

  11. R. Klein, K.E. Lee, R.E. Gangnon, B.E. Klein, The 25-year incidence of visual impairment in type 1 diabetes mellitus: the wisconsin epidemiologic study of diabetic retinopathy. Ophthalmology 117, 63–70 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  12. M. Heniricsson, L. Nyström, G. Blohmé, J. Ostman, C. Kullberg, M. Svensson, A. Schölin, H.J. Arnqvist, E. Björk, J. Bolinder, J.W. Eriksson, G. Sundkvist, The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS). Diabetes Care 26, 349–354 (2003)

    Article  Google Scholar 

  13. F. Ismail-Beigi, T. Craven, M.A. Banerji, J. Basile, J. Calles, R.M. Cohen, R. Cuddihy, W.C. Cushman, S. Genuth, R.H. Grimm, B.P. Hamilton, B. Hoogwerf, D. Karl, L. Katz, A. Krikorian, P. O’Connor, R. Pop-Busui, U. Schubart, D. Simmons, H. Taylor, A. Thomas, D. Weiss, I. Hramiak, ACCORD trial group, Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 376, 419–430 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  14. A. Patel, S. MacMahon, J. Chalmers, B. Neal, L. Billot, M. Woodward, M. Marre, M. Cooper, P. Glasziou, D. Grobbee, P. Hamet, S. Harrap, S. Heller, L. Liu, G. Mancia, C.E. Mogensen, C. Pan, N. Poulter, A. Rodgers, B. Williams, S. Bompoint, B.E. de Galan, R. Joshi, F. Travert, ADVANCE Collaborative Group, Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 358, 2560–2572 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. M. Shichiri, H. Kishikawa, Y. Ohkubo, N. Wake, Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients. Diabetes Care 23, B21–B29 (2000)

    PubMed  Google Scholar 

  16. UK Propective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837–853 (1998)

    Article  Google Scholar 

  17. N. Emanuele, R. Klein, C. Abraira, J. Colwell, J. Comstock, W.G. Henderson, S. Levin, F. Nuttall, C. Sawin, C. Silbert, H.S. Lee, N. Johnson-Nagel, Evaluations of retinopathy in the VA Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VA CSDM). A feasibility study. Diabetes Care 19, 1375–1381 (1996)

    Article  CAS  PubMed  Google Scholar 

  18. W. Duckworth, C. Abraira, T. Moritz, D. Reda, N. Emanuele, P.D. Reaven, F.J. Zieve, J. Marks, S.N. Davis, R. Hayward, S.R. Warren, S. Goldman, M. McCarren, M.E. Vitek, W.G. Henderson, G.D. Huang, VADT investigators, glucose control and vascular complications in veterans with type 2 diabetes. N. Eng. J. Med. 360, 129–139 (2009)

    Article  CAS  Google Scholar 

  19. O. Brinchmann-Hansen, K. Dahl-Jørgensen, L. Sandvik, K.F. Hanssen, Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study. BMJ 304, 19–22 (1992)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. P. Reichard, B.Y. Nilsson, U. Rosenqvist, The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N. Engl. J. Med. 329, 304–309 (1993)

    Article  CAS  PubMed  Google Scholar 

  21. N.H. White, W. Sun, P.A. Cleary, R.P. Danis, M.D. Davis, D.P. Hainsworth, L.D. Hubbard, J.M. Lachin, D.M. Nathan, Prolonged effect of intensive therapy on the risk of retinopathy complications in patients with type 1 diabetes mellitus: 10 years after the Diabetes Control and Complications Trial. Arch. Ophthalmol. 126, 1707–1715 (2008)

    Article  PubMed  Google Scholar 

  22. J.P.T. Higgins, S. Green, Cochrane handbook for systematic reviews of intervention 5.1.0 (2011) Cochrane Collaboration. [Online] Available from http://handbook.cochrane.org. Accessed 20 December 2013

  23. D. Moher, A. Liberati, J. Tetzlaff, D.G. Altman, PRISMA Group, Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339, b2535 (2009)

    Article  PubMed Central  PubMed  Google Scholar 

  24. T. Zhao, J. Zhao, Association of the apolipoprotein A5 gene -1131 T > C polymorphism with fasting blood lipids: a meta-analysis in 37859 subjects. BMC Med. Genet. 11, 120 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  25. J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman, Measuring inconsistency in meta-analyses. BMJ 327, 557–560 (2003)

    Article  PubMed Central  PubMed  Google Scholar 

  26. E.Y. Chew, W.T. Ambrosius, M.D. Davis, R.P. Danis, S. Gangaputra, C.M. Greven, L. Hubbard, B.A. Esser, J.F. Lovato, L.H. Perdue, D.C. Goff, W.C. Cushman, H.N. Ginsberg, M.B. Elam, S. Genuth, H.C. Gerstein, U. Schubart, L.J. Fine, ACCORD Study Group, ACCORD Eye Study Group, Effects of medical therapies on retinopathy progression in type 2 diabetes. N. Engl. J. Med 363, 233–244 (2010)

    Article  PubMed  Google Scholar 

  27. J.W. Beulens, A. Patel, J.R. Vingerling, J.K. Cruickshank, A.D. Hughes, A. Stanton, J. Lu, S.A. McG Thom, D.E. Grobbee, R.P. Stolk, Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetologia 52, 2027–2036 (2009)

    Article  CAS  PubMed  Google Scholar 

  28. UK Prospective Diabetes Study (UKPDS) Group, Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 352, 854–865 (1998)

    Article  Google Scholar 

  29. Early Treatment Diabetic Retinopathy Study Research Group, Grading diabetic retinopathy from stereoscopic color fundus photographs-an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 98, 786–806 (1991)

    Article  Google Scholar 

  30. Early Treatment Diabetic Retinopathy Study Research Group, Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology 98, 823–833 (1991)

    Article  Google Scholar 

  31. P.H. Wang, J. Lau, T.C. Chalmers, Metaanalysis of the effects of intensive glycemic control on late complications of type I diabetes mellitus. Lancet 341, 1306–1309 (1993)

    Article  CAS  PubMed  Google Scholar 

  32. L.P. Aiello, DCCT/EDIC Research Group, Diabetic retinopathy and other ocular findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care 37, 17–23 (2014)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. A.M. Buehler, A.B. Cavalcanti, O. Berwanger, M. Figueiro, L.N. Laranjeira, A.D. Zazula, B. Kioshi, D.G. Bugano, E. Santucci, G. Sbruzzi, H.P. Guimaraes, V.O. Carvalho, S.A. Bordin, Effect of tight blood glucose control versus conventional control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of RCTs. Cardiovasc. Ther. 31, 147–160 (2013)

    Article  CAS  PubMed  Google Scholar 

  34. B. Hemmingsen, S.S. Lund, C. Gluud, A. Vaag, T. Almdal, C. Hemmingsen, J. Wetterslev, Intensive glycaemic control for patients with T2DM: systematic review with meta-analysis and trial sequential analysis of randomised clinical trials. BMJ 343, d6898 (2011)

    Article  PubMed Central  PubMed  Google Scholar 

  35. The Diabetes Control and Complications Trial Research Group, Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch. Ophthalmol. 116, 874–886 (1998)

    Article  Google Scholar 

  36. E. Moskalets, G. Galstyan, E. Starostina, M. Antsiferov, E. Chantelau, Association of blindness to intensification of glycemic control in insulin-dependent diabetes mellitus. J. Diabetes Complications 8, 45–50 (1994)

    Article  CAS  PubMed  Google Scholar 

  37. M. Henricsson, A. Nilsson, L. Janzon, L. Groop, The effect of glycaemic control and the introduction of insulin therapy on retinopathy in non-insulin-dependent diabetes mellitus. Diabet. Med. 14, 123–131 (1997)

    Article  CAS  PubMed  Google Scholar 

  38. M. Henricsson, K. Berntorp, E. Berntorp, P. Fernlund, G. Sundkvist, Progression of retinopathy after improved metabolic control in type 2 diabetic patients. Relation to IGF-1 and hemostatic variables. Diabetes Care 22, 1944–1949 (1999)

    Article  CAS  PubMed  Google Scholar 

  39. J. Tovi, S.O. Ingemansson, P. Engfeldt, Insulin treatment of elderly type 2 diabetic patients: effects on retinopathy. Diabetes Metab. 24, 442–447 (1998)

    CAS  PubMed  Google Scholar 

  40. S. Savage, R.O. Estacio, B. Jeffers, R.W. Schrier, Increased complications in noninsulin-dependent diabetic patients treated with insulin versus oral hypoglycemic agents: a population study. Proc. Assoc. Am. Physicians 109, 181–189 (1997)

    CAS  PubMed  Google Scholar 

  41. E. Chantelau, E.M. Kohner, Why some cases of retinopathy worsen when diabetic control improves. BMJ 315, 1105–1106 (1997)

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. M. Paques, P. Massin, A. Gaudric, Growth factors and diabetic retinopathy. Diabetes Metab. 23, 125–130 (1997)

    CAS  PubMed  Google Scholar 

  43. R. Simó, J.M. Sundstrom, D.A. Antonetti, Ocular anti-VEGF therapy for diabetic retinopathy: the role of VEGF in the pathogenesis of diabetic retinopathy. Diabetes Care 37, 893–899 (2014)

    Article  PubMed  Google Scholar 

  44. The Kroc Collaborative Study Group, Follow-up of the Kroc Collaborative Study, Diabetic retinopathy after two years of intensified insulin treatment. JAMA 260, 37–41 (1988)

    Article  Google Scholar 

  45. E.Y. Chew, W.T. Ambrosius, R.P. Danis, Retinopathy progression in type 2 diabetes. N. Engl. J. Med. 25, 2173–2174 (2010)

    Google Scholar 

  46. Diabetes Control and Complications Trial Research Group, Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology 102, 647–661 (1995)

    Article  Google Scholar 

  47. R.R. Holman, S.K. Paul, M.A. Bethel, D.R. Matthews, H.A. Neil, 10-year follow-up of intensive glucose control in type 2 diabetes. N. Eng. J. Med. 359, 1577–1589 (2008)

    Article  CAS  Google Scholar 

  48. Diabetes Control and Complications Trail Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Eng. J. Med. 329, 977–986 (1993)

    Article  Google Scholar 

  49. N. Cheung, P. Mitchell, T.Y. Wong, Diabetic retinopathy. Lancet 376, 124–136 (2010)

    Article  PubMed  Google Scholar 

  50. V.S. Jeganathan, J.J. Wang, T.Y. Wong, Ocular association of diabetes other than diabetic retinopathy. Diabetes Care 31, 1905–1912 (2008)

    Article  PubMed Central  PubMed  Google Scholar 

  51. C. Rotimi, H. Daniel, J. Zhou, A. Obisesan, G. Chen, Y. Chen, A. Amoah, V. Opoku, J. Acheampong, K. Agyenim-Boateng, B.A. Eghan, J. Oli, G. Okafor, E. Ofoegbu, B. Osotimehin, F. Abbiyesuku, T. Johnson, O. Fasanmade, A. Doumatey, T. Aje, F. Collins, G. Dunston, Prevalence and determinants of diabetic retinopathy and cataracts in West African type 2 diabetes patients. Ethn. Dis. 13, S110–S117 (2003)

    PubMed  Google Scholar 

  52. B. Sonmez, B. Bozkurt, A. Atmaca, M. Irkec, M. Orhan, U. Aslan, Effect of glycemic control on refractive changes in diabetic patients with hyperglycemia. Cornea 24, 531–537 (2005)

    Article  PubMed  Google Scholar 

  53. S. Kato, T. Oshika, J. Numaga, H. Kawashima, S. Kitano, T. Kaiya, Influence of rapid glycemic control on lens opacity in patients with diabetes mellitus. Am. J. Ophthalmol. 130, 354–355 (2000)

    Article  CAS  PubMed  Google Scholar 

  54. K. Skarbez, Y. Priestley, M. Hoepf, S.B. Koevary, Comprehensive review of the effects of diabetes on ocular health. Expert Rev. Ophthalmol. 5, 557–577 (2010)

    Article  PubMed Central  PubMed  Google Scholar 

  55. American Diabetes Association, Executive summary: standards of medical care in diabetes-2009. Diabetes Care 32, S6–S12 (2009)

    Article  Google Scholar 

  56. P.S. Jellinger, J.A. Davidson, L. Blonde, D. Einhorn, G. Grunberger, Y. Handelsman, R. Hellman, H. Lebovitz, P. Levy, V.L. Roberts, ACE/AACE Diabetes Road MapTask Force, Road maps to achieve glycemic control in type 2 diabetes mellitus: ACE/AACE Diabetes Road Map Task Force. Endocr. Pract. 13, 260–268 (2007)

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Xiaoyan Wang from Guangdong Institute of Gastroenterology for her kind instruction and advice in statistical analysis.

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The authors declare that there is no conflict of interest associated with this manuscript.

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Authors and Affiliations

  1. Department of Endocrinology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Erheng Yuancun Road, Guangzhou, 510655, China

    Xiaodan Zhang & Tongfeng Zhao

  2. Department of Neurology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China

    Jiangpei Zhao

  3. The Sixth Affiliated Hospital and Guangdong Institute of Gastroenterology, Sun Yat-sen University, 26 Erheng Yuancun Road, Guangzhou, 510655, China

    Huanliang Liu

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  1. Xiaodan Zhang
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Zhang, X., Zhao, J., Zhao, T. et al. Effects of intensive glycemic control in ocular complications in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. Endocrine 49, 78–89 (2015). https://doi.org/10.1007/s12020-014-0459-8

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