Mechanism of worsening diabetic retinopathy with rapid lowering of blood glucose: the synergistic hypothesis.

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diabetic retinopathy 39 endocrinologydiseases
hyperglycemia 1 endocrinologydiseases
Insulin 3 endocrinologydiseasesdrugs
diabetes mellitus 1 endocrinologydiseases

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Insulin 325 date (epub): 10/2017Publication date (pmc-release): 10/2017Publication date (collection): /2017Abstract Insulin treatment has been associated with a paradoxical worsening of diabetes retinopathy since many years
Insulin 3118 diabetic retinopathy and insulin use, and we propose a novel hypothesis to support this relationship. Insulin use and early worsening of diabetes retinopathy: Paradoxical report with growing evidenceIt is established
Insulin 8921 could have important therapeutic implications.What do we learn from basic science research on the topic? Insulin has been known for many years as an anabolic hormone necessary for growth. Experiences showed that growth
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diabetes mellitus 1533 where it remains underdiagnosed, under investigated, and undertreated [[3]–[5]]. The epidemic rise in diabetes mellitus poses significant public health and socioeconomic challenges through diabetic complications affecting
diabetic retinopathy 53 Title: BMC Endocrine DisordersMechanism of worsening diabetic retinopathy with rapid lowering of blood glucose: the synergistic hypothesisAhmadou M. JingiAurel T. TankeuNarcisse
diabetic retinopathy 2261 hyper-permeability, retinal neovascularization, and macular edema. If left untreated patients with diabetic retinopathy can suffer severe visual loss [[7]]. In developed countries, diabetic retinopathy constitutes the leading
diabetic retinopathy 2343 untreated patients with diabetic retinopathy can suffer severe visual loss [[7]]. In developed countries, diabetic retinopathy constitutes the leading cause of blindness in the working age population [[8]]. Different risk and progression
diabetic retinopathy 2487 cause of blindness in the working age population [[8]]. Different risk and progression factors for diabetic retinopathy have been documented and classified as modifiable risk factors (blood glucose, blood pressure, serum
diabetic retinopathy 2799 predisposition, and ethnicity) [[9]]. However, recent literature has clearly demonstrated an incremented risk of diabetic retinopathy with regard to insulin treatment [[1], [10]–[12]]. Nevertheless, the mechanism underlying this paradoxical
diabetic retinopathy 3017 paradoxical association is not well understood. Here we revisit evidence on the association between diabetic retinopathy and insulin use, and we propose a novel hypothesis to support this relationship.Insulin use and early
diabetic retinopathy 3238 early worsening of diabetes retinopathy: Paradoxical report with growing evidenceIt is established that diabetic retinopathy and related complications are strongly associated with the presence of chronic hyperglycemia, and results
diabetic retinopathy 4006 with insulin is associated with recurrent hypoglycemic episodes, and the risk of early worsening of diabetic retinopathy . This later has been reported in the Diabetes Control and Complications Trial (DCCT) where this occurred
diabetic retinopathy 4500 [[19]]. Similar finding were later reported by Wang et al. in a meta-analysis who found that the risk of diabetic retinopathy progression tends to increase after 6 to 12 months of intensive therapy with insulin (odds ratio: 2.11;
diabetic retinopathy 4723 2.11; 95% confidence interval: 0.54 to 8.31) compared to conventional treatment. Yet, this increase in diabetic retinopathy risk was also reversed after 2 years of intensive treatment with insulin. Recently, data on this paradoxical
diabetic retinopathy 5208 support previous findings and highlight the early worsening effect of insulin on the progression of diabetic retinopathy [[1], [10], [26]].The role of osmotic force theory: Basis and limitsIn view of the difficulty in explaining
diabetic retinopathy 5368 force theory: Basis and limitsIn view of the difficulty in explaining the paradoxical aggravation of diabetic retinopathy at the initiation of insulin therapy, osmotic theory was proposed based on physiological approach, and
diabetic retinopathy 5940 milieu can modify the osmotic pressure and act on water retention. To explain the early worsening of diabetic retinopathy with intensive treatment, it has been suggested that the rapid drop in plasma glucose concentration
diabetic retinopathy 6699 explain major changes in diabetes retinopathy as well as the increase in this paradoxical worsening of diabetic retinopathy with insulin compared to oral anti-diabetic agents.First of all, the osmotic drive force of glucose
diabetic retinopathy 6981 changes, but cannot explain the appearance of neo-vessels and other retinal features associated with diabetic retinopathy . In addition, it is worth noting that a rapid reduction of blood glucose by up to 4 g/l will not result
diabetic retinopathy 7437 change in glucose concentration. On the other hand, this theory cannot explain the higher incidence of diabetic retinopathy in patients on insulin rather as compared to those on oral anti-diabetic agents.A synergistic hypothesis
diabetic retinopathy 7720 of early worsening of diabetes retinopathyPrevious reports on the increased incidence and worsening diabetic retinopathy with insulin compared with oral anti-diabetic agents have led to the hypothesis that insulin is probably
diabetic retinopathy 7911 hypothesis that insulin is probably related to the occurrence of this paradoxical early worsening in diabetic retinopathy with rapid lowering of blood pressure. But the exact mechanism underlying this report is not well understood.
diabetic retinopathy 8391 synergistically with VEGF expressed by ischemic retina so as to trigger vascular proliferation and worsening of diabetic retinopathy . This explains the role of insulin, the different clinical features found on retinal examination, why
diabetic retinopathy 8514 This explains the role of insulin, the different clinical features found on retinal examination, why diabetic retinopathy is more pronounced in individuals with pre-existing retinal lesions (worsening) and rare in individuals
diabetic retinopathy 9782 the formation on new vessels by increasing the expression of VEGF. This may explain the occurrence of diabetic retinopathy with new vessels in presence of insulin and not with oral antidiabetic agents. The in vitro study of
diabetic retinopathy 10084 retinal microvascular endothelial cells as the hallmark in the pathophysiology of insulin-associated diabetic retinopathy [[29]]. They showed that insulin interacts with the NADPH oxidase subunit 4 (Nox-4) to induce excess
diabetic retinopathy 10793 for a growth to occur and is able to stimulate the growth of new vessels. Probably the worsening of diabetic retinopathy attributed to insulin use might result from ROS signaling via activation VEGF expression. This is a
diabetic retinopathy 11006 This is a possible mechanism by which insulin administration can cause neovascularization as found in diabetic retinopathy .Evidence from epidemiological studiesMany epidemiological studies supported the fact that insulin therapy
diabetic retinopathy 11189 studies supported the fact that insulin therapy is a key factor in the occurrence of early worsening of diabetic retinopathy . To illustrate that, patients with type 1 diabetes who are almost exclusively treated with exogenous
diabetic retinopathy 11345 type 1 diabetes who are almost exclusively treated with exogenous insulin are more prone to develop diabetic retinopathy after initiation of treatment as opposed to those with type 2 diabetes. For instance, at diagnosis of
diabetic retinopathy 11526 2 diabetes. For instance, at diagnosis of type 1 diabetes, most of patients do not have evidence of diabetic retinopathy . But, after 15 years of evolution and treatment of type 1 diabetes, over 90% of patients have evidence
diabetic retinopathy 11654 after 15 years of evolution and treatment of type 1 diabetes, over 90% of patients have evidence of diabetic retinopathy [[3]]. In comparison, at the diagnosis of type 2 diabetes (preclinical phase of up to 12 years), up
diabetic retinopathy 11812 diagnosis of type 2 diabetes (preclinical phase of up to 12 years), up to 20% of patients have evidence of diabetic retinopathy , and 15 years after the diagnosis (cumulated estimate of 27 years of evolution), only 60% of patients
diabetic retinopathy 11954 the diagnosis (cumulated estimate of 27 years of evolution), only 60% of patients have evidence of diabetic retinopathy [[3]]. In addition, diabetic retinopathy is usually worse in adolescents and young adults compared to
diabetic retinopathy 11995 27 years of evolution), only 60% of patients have evidence of diabetic retinopathy [[3]]. In addition, diabetic retinopathy is usually worse in adolescents and young adults compared to older individuals without any plausible
diabetic retinopathy 12804 more likely to be treated with oral hypoglycemic agents, are more likely to have other risk factors of diabetic retinopathy , and are less likely to experience growth hormonal surge. The “synergistic effect” is thus less
diabetic retinopathy 13194 of treatment. Despite the longer duration of type 2 diabetes and possible associated risk factors of diabetic retinopathy , the rate and severity of diabetic retinopathy is lesser than in type 1 diabetes. This could also explain
diabetic retinopathy 13241 type 2 diabetes and possible associated risk factors of diabetic retinopathy, the rate and severity of diabetic retinopathy is lesser than in type 1 diabetes. This could also explain the occurence of diabetic retinopathy found
diabetic retinopathy 13338 of diabetic retinopathy is lesser than in type 1 diabetes. This could also explain the occurence of diabetic retinopathy found during pregnancy in some studies.In a recent study, we reported and discussed the worsening of
diabetic retinopathy 13460 found during pregnancy in some studies.In a recent study, we reported and discussed the worsening of diabetic retinopathy observed after rapid lowering of blood glucose with insulin [[2]]. In a group of sub-Saharan African
diabetic retinopathy 13634 insulin [[2]]. In a group of sub-Saharan African patients with type 2 diabetes who were screened for diabetic retinopathy using angiography, we observed that those treated with insulin alone had higher rates and more severe
diabetic retinopathy 13766 angiography, we observed that those treated with insulin alone had higher rates and more severe forms of diabetic retinopathy than those on oral agents alone [[2]]. This suggests that the “synergistic effect” is more pronounced
diabetic retinopathy 14072 alone.ConclusionsThe synergistic hypothesis appears to better explain the occurrence and worsening of diabetic retinopathy observed with the rapid lowering of blood glucose than the long held osmotic hypothesis, which only
hyperglycemia 3338 diabetic retinopathy and related complications are strongly associated with the presence of chronic hyperglycemia , and results of almost all randomized trials are consistent with the fact that early and intensive glycemic

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