Why some cases of retinopathy worsen when diabetic control improves

Chantelau, Ernst; Kohner, E M

doi:10.1136/bmj.315.7116.1105

Cited by 64 publications

(27 citation statements)

References 15 publications

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“…However, a study in which retinal blood flow was measured before and after rapid improvement of control showed that blood flow increased, rather than decrease, in the patients who developed early worsening [91], suggesting a pathogenic role for increased shear stress on the capillary wall. Others have suggested that increased insulin concentrations augment hepatic synthesis and release of insulin-like growth factor I (IGF-I), which could be involved in fibro-vascular proliferation [92], and retinal expression of VEGF [93].…”

Section: Early Worsening Of Diabetic Retinopathymentioning

confidence: 99%

Diabetic retinopathy

2002

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Abstract. Easy observation of the fundus oculi makes retinopathy the most frequently reported chronic complication of diabetes and, consequently, the one we know best in terms of epidemiology and natural history. Achieving near-normal levels of blood glucose and blood pressure provides empirical though powerful tools for clinicians to delay the onset and progression of diabetic retinopathy. Even when these measures have failed and retinopathy becomes sight-threatening, laser photocoagulation has proven remarkably effective. Nonetheless, retinopathy remains a leading cause of blindness and there is little evidence that diabetes-related visual loss is decreasing in industrialized countries. This may result from the mixed blessing of prolonged survival of patients who had become diabetic when metabolic control was pursued less fastidiously than today. Screening for sight-threatening retinopathy is the most cost-effective medical procedure known and should help optimise the use of diagnostic and therapeutic resources, but its widest deployment still meets with inertia and lack of interest within most health care systems. Improving clinical skills and technology, however, allow us to take a more optimistic look at the future, as pathogenesis-targeted forms of treatment are being developed and tested through appropriately powered clinical trials. [Diabetologia (2002[Diabetologia ( ) 45:1617[Diabetologia ( -1634

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Section: Early Worsening Of Diabetic Retinopathymentioning

confidence: 99%

Diabetic retinopathy

2002

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“…Increased IGF-1 serum levels during pregnancy in type 1 diabetes correlate with progression of diabetic retinopathy (13). Similarly, the paradoxical initial increase in retinal neovascularization observed shortly after intensive insulin therapy in patients with poorly controlled diabetes is consistent with the rise in serum IGF-1 levels (14)(15)(16)(17)(18)(19)(20). Moreover, hypoxia-stimulated retinal neovascularization is inhibited in mice expressing a growth-hormone antagonist gene or in normal mice given an inhibitor of growth-hormone secretion, both leading to low circulating IGF-1 (21).…”

Section: Introductionmentioning

confidence: 73%

Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease

Ruberte

Ayuso²,

Navarro³

et al. 2004

J. Clin. Invest.

148

115

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IGF-1 has been associated with the pathogenesis of diabetic retinopathy, although its role is not fully understood. Here we show that normoglycemic/normoinsulinemic transgenic mice overexpressing IGF-1 in the retina developed most alterations seen in human diabetic eye disease. A paracrine effect of IGF-1 in the retina initiated vascular alterations that progressed from nonproliferative to proliferative retinopathy and retinal detachment. Eyes from 2-month-old transgenic mice showed loss of pericytes and thickening of basement membrane of retinal capillaries. In mice 6 months and older, venule dilatation, intraretinal microvascular abnormalities, and neovascularization of the retina and vitreous cavity were observed. Neovascularization was consistent with increased IGF-1 induction of VEGF expression in retinal glial cells. In addition, IGF-1 accumulated in aqueous humor, which may have caused rubeosis iridis and subsequently adhesions between the cornea and iris that hampered aqueous humor drainage and led to neovascular glaucoma. Furthermore, all transgenic mice developed cataracts. These findings suggest a role of IGF-1 in the development of ocular complications in long-term diabetes. Thus, these transgenic mice may be used to study the mechanisms that lead to diabetes eye disease and constitute an appropriate model in which to assay new therapies.Nonstandard abbreviations used: glial fibrillar acidic protein (GFAP); intraocular pressure (IOP); intraretinal microvascular abnormalities (IRMAs); rat insulin promoter-I (RIP-I); streptozotocin (STZ); von Willebrand factor (vWF).

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“…One potentially adverse effect of INT on macrovascular outcomes in our patients is a significant rise in fibrinogen levels after 1 year that returned to baseline at 2 years (39). This and other factors could produce early worsening of macrovascular diseases as observed for microvascular events in the Diabetes Control and Complications Trial (40).…”

Section: Conclusion -mentioning

confidence: 98%

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators.

et al. 2000

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OBJECTIVE -Microalbuminuria can reflect the progress of microvascular complications and may be predictive of macrovascular disease in type 2 diabetes. The effect of intensive glycemic control on microalbuminuria in patients in the U.S. who have had type 2 diabetes for several years has not previously been evaluated. RESEARCH DESIGN AND METHODS-We randomly assigned 153 male patients to either intensive treatment (INT) (goal HbA 1c 7.1%) or to standard treatment (ST) (goal HbA 1c 9.1%; P = 0.001), and data were obtained during a 2-year period. Mean duration of known diabetes was 8 years, mean age of the patients was 60 years, and patients were well matched at baseline. We obtained 3-h urine samples for each patient at baseline and annually and defined microalbuminuria as an albumin:creatinine ratio of 0.03-0.30. All patients were treated with insulin and received instructions regarding diet and exercise. Hypertension and dyslipidemia were treated with similar goals in each group.RESULTS -A total of 38% of patients had microalbuminuria at entry and were evenly assigned to both treatment groups. INT retarded the progression of microalbuminuria during the 2-year period: the changes in albumin:creatinine ratio from baseline to 2 years of INT versus ST were 0.045 vs. 0.141, respectively (P = 0.046). Retardation of progressive urinary albumin excretion was most pronounced in those patients who entered the study with microalbuminuria and were randomized to INT. Patients entering with microalbuminuria had a deterioration in creatinine clearance at 2 years regardless of the intensity of glycemic control. In the group entering without microalbuminuria, the subgroup receiving ST had a lower percentage of patients with a macrovascular event (17%) than the subgroup receiving INT (36%) (P = 0.03). Use of ACE inhibitors or calcium-channel blockers was similarly distributed among the groups.CONCLUSIONS -Intensive glycemic control retards microalbuminuria in patients who have had type 2 diabetes for several years but may not lessen the progressive deterioration of glomerular function. Increases in macrovascular event rates in the subgroup entering without albuminuria who received INT remain unexplained but could reflect early worsening, as observed with microvascular disease in the Diabetes Control and Complications Trial.

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Why some cases of retinopathy worsen when diabetic control improves

Cited by 64 publications

References 15 publications

Diabetic retinopathy

Diabetic retinopathy

Increased ocular levels of IGF-1 in transgenic mice lead to diabetes-like eye disease

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators.

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