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   Table of Contents      
Year : 2016  |  Volume : 64  |  Issue : 6  |  Page : 476-477

Comment to: Dual effect hypothesis of insulin analogs on diabetic retinopathy

Department of Ophthalmology, Anıttepe Military Dispensary, Ankara, Turkey

Date of Web Publication3-Aug-2016

Correspondence Address:
Abdullah Kaya
Department of Ophthalmology, Anıttepe Military Dispensary, Ankara
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.187693

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How to cite this article:
Kaya A. Comment to: Dual effect hypothesis of insulin analogs on diabetic retinopathy. Indian J Ophthalmol 2016;64:476-7

How to cite this URL:
Kaya A. Comment to: Dual effect hypothesis of insulin analogs on diabetic retinopathy. Indian J Ophthalmol [serial online] 2016 [cited 2020 Aug 15];64:476-7. Available from: http://www.ijo.in/text.asp?2016/64/6/476/187693


I read the current review article titled "Does tight control of systemic factors help in the management of diabetic retinopathy?" by Rajalakshmi et al. with great interest. [1] Authors present the impact of tight control of systemic factors on progression of diabetic retinopathy (DRP). I congratulate the authors for this lightening review and want to make a contribution.

One of the systemic factors discussed in the article is the glycemic control. Authors stated intensive glycemic control to reduce development and progression of DRP. They also stated that tight glycemic control is most effective when initiated early, but it may at times have adverse effects, including worsening of DRP. According to this statement, tight glycemic control seems to have "dual effect" on progression of DRP that associate with the duration of treatment. We previously hypothesized a mechanism as "dual effect of insulin analogs on progression of DRP" that may explain this phenomenon. [2] As authors addressed in the article, upregulation of insulin-like growth factor-1 (IGF-1) may be the reason of early worsening of DRP. Insulin and its analogs stimulate IGF-1 receptors. Especially some insulin analogs, being developed by changing amino acid chain, are more potent than human insulin. Insulin glargine was reported to be 10 times more potent than human insulin to stimulate IGF-1 receptor. [3] IGF-1 signaling may cause the progression of DRP. IGF-1 is a receptor of growth hormone (GH). An association between GH and DRP has being known for a long time. DRP regresses after spontaneous infarction or surgical ablation of pituitary gland. [4] In dwarfs, GH deficiency is a protective factor for the development of DRP. [5] Despite the same glycemic control, development of DRP is significantly higher in pubertal subjects than prepubertal subjects. [6] GH acts on IGF-1 receptor. Insulin analogs also stimulate IGF-1 receptor and may cause progression of DRP through GH-like effect. Insulin analogs may change cellular composition of retina through stimulation of IGF-1 receptors. IGF-1 has been reported to stimulate and proliferate a type of glial cell named nonastrocytic inner retinal glia-like. [7] Traction force in retinal pigment epithelium and Mullerian cells generates by IGF-1 signaling. [8]

Gadkari et al. recently reported insulin usage as a risk factor for progression of DRP in Indian population. [9] Insulin analogs may deteriorate DRP through IGF-1. However, analogs should pass into the retinal tissue to show this effect. Inner blood retinal barrier (IRB) may prevent analogs to pass retinal tissue. When IRB is intact, analogs may not deteriorate DRP through IGF-1 signaling, also protect retina by lowering blood glucose, and prevent harmful effect of hyperglycemia. After impairment of IRB, analogs may pass into the retina and cause progression of DRP by stimulating IGF-1 receptor. We named this mechanism as "dual effect hypothesis of insulin analogs on DRP" that associate with impairment degree of IRB.

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  References Top

Rajalakshmi R, Prathiba V, Mohan V. Does tight control of systemic factors help in the management ofdiabetic retinopathy? Indian J Ophthalmol 2016;64:62-8.  Back to cited text no. 1
[PUBMED]  Medknow Journal  
Kaya A, Kar T, Aksoy Y, Özalper V, Basbug B. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier. Med Hypotheses 2013;81:1012-4.  Back to cited text no. 2
Varewijck AJ, Goudzwaard JA, Brugts MP, Lamberts SW, Hofland LJ, Janssen JA. Insulin glargine is more potent in activating the human IGF-I receptor than human insulin and insulin detemir. Growth Horm IGF Res 2010;20:427-31.  Back to cited text no. 3
Adams DA, Rand RW, Roth NH, Dashe AM, Gipstein RM, Heuser G. Hypophysectomy in diabetic retinopathy. The relationship between the degree of pituitary ablation and ocular response. Diabetes 1974;23:698-707.  Back to cited text no. 4
Merimee TJ. A follow-up study of vascular disease in growth- hormone-deficient dwarfs with diabetes. N Engl J Med 1978;298:1217-22.  Back to cited text no. 5
Murphy RP, Nanda M, Plotnick L, Enger C, Vitale S, Patz A. The relationship of puberty to diabetic retinopathy. Arch Ophthalmol 1990;108:215-8.  Back to cited text no. 6
Fischer AJ, Scott MA, Zelinka C, Sherwood P. A novel type of glial cell in the retina is stimulated by insulin-like growth factor 1 and may exacerbate damage to neurons and Müller glia. Glia 2010;58:633-49.  Back to cited text no. 7
Mukherjee S, Guidry C. The insulin-like growth factor system modulates retinal pigment epithelial cell tractional force generation. Invest Ophthalmol Vis Sci 2007;48:1892-9.  Back to cited text no. 8
Gadkari SS, Maskati QB, Nayak BK. Prevalence of diabetic retinopathy in India: The All India Ophthalmological Society Diabetic Retinopathy Eye Screening Study 2014. Indian J Ophthalmol 2016;64:38-44.  Back to cited text no. 9
[PUBMED]  Medknow Journal  


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