Progression of Incipient Diabetic Retinopathy During Good Glycemic Control

Engerman, Ronald L.; Kern, Timothy S.

doi:10.2337/diab.36.7.808

Cited by 389 publications

(153 citation statements)

References 19 publications

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“…This hypothesis is consistent with a previous finding that the return to good glycaemic control in rats after 6 months of very poor control was ineffective in decreasing 3-NY levels or other markers of oxidative stress in the retina of these diabetic animals [12]. Moreover, the effect of ALA in our study supports the finding of Lin et al, showing protective effects of ALA in experimental diabetic retinopathy through the inhibition of oxidative and nitrosative stress [36].…”

Section: Discussionsupporting

confidence: 94%

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Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling

et al. 2007

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Aims/hypothesis A long-term 'memory' of hyperglycaemic stress, even when glycaemia is normalised, has been previously reported in endothelial cells. In this report we sought to duplicate and extend this finding. Materials and methods HUVECs and ARPE-19 retinal cells were incubated in 5 or in 30 mmol/l glucose for 3 weeks or subjected to 1 week of normal glucose after being exposed for 2 weeks to continuous high glucose. HUVECs were also treated in this last condition with several antioxidants. Similarly, four groups of rats were studied for 3 weeks: (1) normal rats; (2) diabetic rats not treated with insulin; (3) diabetic rats treated with insulin during the last week; and (4) diabetic rats treated with insulin plus α-lipoic acid in the last week. Results In human endothelial cells and ARPE-19 retinal cells in culture, as well as in the retina of diabetic rats, levels of the following markers of high glucose stress remained induced for 1 week after levels of glucose had normalised: protein kinase C-β, NAD(P)H oxidase subunit p47phox, BCL-2-associated X protein, 3-nitrotyrosine, fibronectin, poly(ADPribose) Blockade of reactive species using different approaches, i.e. the mitochondrial antioxidant α-lipoic acid, overexpression of uncoupling protein 2, oxypurinol, apocynin and the poly(ADP-ribose) polymerase inhibitor PJ34, interrupted the induction both of high glucose stress markers and of the fluorescent reactive oxygen species (ROS) probe CM-H 2 DCFDA in human endothelial cells. Similar results were obtained in the retina of diabetic rats with α-lipoic acid added to the last week of normalised glucose. Conclusions/interpretation These results provide proofof-principle of a ROS-mediated cellular persistence of vascular stress after glucose normalisation.

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Section: Discussionsupporting

confidence: 94%

“…These data are consistent with findings that retinopathy progression can persist in dogs even after the normalisation of glycaemic control [12].…”

Section: Introductionsupporting

confidence: 92%

Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling

et al. 2007

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“…Furthermore, our results seem to indicate that a critical concentration of AGEs in the plasma is necessary for AGEs accumulation in the tissues and subsequent tissue damage to occur. It is also likely that accumulation of AGEs in tissues explains the progression of hyperglycaemia-induced alterations during normal glucose homeostasis [26,27]. Indeed, in our delayed insulin treatment group (group 20/8) serum AGEs were high and there was accumulation of AGEs in the MPG even though serum glucose concentrations had been normalized.…”

Section: Discussionmentioning

confidence: 72%

Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: A new insight into selective nitrergic neuropathy in diabetes

et al. 2004

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Aims/hypothesis. We have previously shown that in diabetes nitrergic neurones innervating the urogenital and gastrointestinal organs undergo a selective degenerative process. This comprises an initial insulin-reversible decrease in neuronal nitric oxide synthase (nNOS) in the axons, followed by apoptosis of the nitrergic neurones, a process that is not reversible by insulin. Since apoptosis was independent of serum glucose concentrations, and advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic complications, we have now measured AGEs in the serum and penis, pyloric sphincter and pelvic ganglia of diabetic animals at different times after streptozotocin treatment. Furthermore, we have studied their effect in vitro on human neuroblastoma (SH-SY5Y) cells in the presence or absence of nNOS expression. Methods. Serum AGEs were measured using fluorometry and ELISA. Accumulation of AGEs in the tissues was evaluated with immunohistochemistry. The viability, apoptosis and oxidative stress in SH-SY5Y cells were measured upon exposure to AGEs or high concentrations of glucose. Results. AGEs increased gradually in the serum and tissues of streptozotocin-induced diabetic rats; this process was not affected by delayed insulin treatment. In SH-SY5Y cells, AGEs, but not high glucose concentrations, increased the reactive oxygen species and caspase-3-dependent apoptosis in a synergistic fashion with endogenous nitric oxide (NO). Apoptosis was prevented by treatment with a NOS inhibitor, a pan-caspase inhibitor, a soluble receptor of AGEs or an anti-oxidant, but not an inhibitor of soluble guanylate cyclase. Conclusions/interpretation. The synergistic actions of NO and AGEs account for the irreversible nitrergic degeneration in diabetes. [Diabetologia (2004) 47: 331-339]

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“…The investigation of certain risk factors was determined by previous publications (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) . For this reason, patients were also questioned about their disease and personal characteristics: type of diabetes (insulin-or non-insulin-dependent), time interval since diagnosis, medication in use and racial ancestry.…”

Section: Methodsmentioning

confidence: 99%

“…It is not possible to define which diabetic individuals will present retinopathy. However, it is possible to determine risk factors related to the development of retinopathy (5) , such as duration of systemic disease, poor diabetes control, insulin-dependent diabetes, dislipidemia, hypertension, alcoholism, pregnancy, associated renal disease, anemia hypomagnesemia and African descendant (1,(8)(9)(10)(11)(12)(13)(14)(15)(16) . Some studies suggest that retinopathy progression is almost inexistent in younger-onset diabetics (less than 13 years-old).…”

Section: Introductionmentioning

confidence: 99%

Risk factors related to the severity of diabetic retinopathy

Corrêa¹,

Freitas²,

Marcon³

2003

Arq. Bras. Oftalmol.

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Risk factors related to the severity of diabetic retinopathyPurpose: To determine the relationship between the severity or stage of diabetic retinopathy and associated risk factors in a southern Brazilian population. Methods: Transversal study of diabetic patients without previous ophthalmologic treatment, seen at a University eye clinic. These patients underwent fundus photography, complete blood work-up, systemic blood pressure measurement, urine analysis, and were questioned about risk factors previously determined by the authors. The presence or absence of risk factors was compared to the severity of diabetic retinopathy. Results: Eighty-one patients were selected, 28 male, 53 female, 55 Caucasians, 26 African descendants, 28 had insulin-dependent diabetes mellitus, 53 had non-insulin-dependent diabetes mellitus. Factors related to more severe diabetic retinopathy include: insulin-dependent diabetes mellitus (α<0.01), nephropathy (α<0.05), proteinuria (α<0.05), duration of the disease (p<0.001), elevated fasting plasma glucose (p=0.11), glycosylated hemoglobin (HbA (1c)) (p=0.001), total serum cholesterol (p=0.019), lower hematocrit (p=0.004) and hemoglobin (p=0.001). Conclusions: The severity of diabetic retinopathy appears to be associated with risk factors such as duration of disease, type of diabetes, poor metabolic control, hemoglobin levels, total cholesterol and proteinuria. Factors apparently not related to severity of diabetic retinopathy include gender, age, systemic hypertension and hypomagnesemia.

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Progression of Incipient Diabetic Retinopathy During Good Glycemic Control

Cited by 389 publications

References 19 publications

Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling

Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling

Synergistic action of advanced glycation end products and endogenous nitric oxide leads to neuronal apoptosis in vitro: A new insight into selective nitrergic neuropathy in diabetes

Risk factors related to the severity of diabetic retinopathy

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