Rapid development and progression of proliferative retinopathy after strict diabetic control.

Dandona, P; Bolger, James; Boag, Fiona; Fonesca, V; Abrams, John

doi:10.1136/bmj.290.6472.895

Cited by 37 publications

(24 citation statements)

References 7 publications

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“…These findings are consistent with the clinical observation that daily fluctuations in plasma glucose concentrations, which occur in diabetic patients, are correlated to increases in cardiovascular disease [23] and microvascular complications [24]. On the other hand, diabetic retinopathy was demonstrated to accelerate, after reducing blood glucose levels, particularly if a rapid improvement in glycaemic control is achieved [25][26][27][28]. Nevertheless, several reports in the literature show a high sensitivity of bovine pericytes also to a direct exposure to high glucose concentrations [6,17,29].…”

Section: Discussionsupporting

confidence: 90%

Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine

Beltramo

Berrone

Tarallo

et al. 2009

Diabetes Metabolism Res

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Human pericytes are less prone to apoptosis induced by persistently high glucose than bovine cells. However, while BRP recover after returning to physiological levels, HRP are more vulnerable to both downwardly fluctuating glucose levels and intermittent exposure. These findings reinforce the hypotheses that (1) glycaemic fluctuations play a role in the development of diabetic retinopathy and (2) species-specific models are needed. Thiamine and benfotiamine prevent human pericyte apoptosis, indicating this vitamin as an inexpensive approach to the prevention and/or treatment of diabetic complications.

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Section: Discussionsupporting

confidence: 90%

Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine

Beltramo

Berrone

Tarallo

et al. 2009

Diabetes Metabolism Res

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“…However, as already mentioned, human retinal pericytes seem to be more sensible to intermittent than stable high glucose concentrations, due to impairment in the Bcl-2/Bax ratio [51,52], while rapid glucose normalization, explained as "ROS -mediated cellular memory" of vascular stress has been shown in EC and retinal ARPE-19 [56], consistently with the clinical observation that daily fluctuations in plasma glucose concentrations in diabetic patients are related to increased risk of cardiovascular disease [57] and microvascular complications [58]. DR itself has been seen to accelerate after restoration of physiological glycaemic levels, mostly if glycaemic control is rapidly achieved [100][101][102][103].…”

Section: Pericyte Loss During Dr: Glucose Metabolism Pathwaysmentioning

confidence: 81%

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Beltramo

Porta

2013

CMC

259

173

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The onset of diabetic retinopathy is characterized by morphologic alterations of the microvessels, with thickening of the basement membrane, loss of inter-endothelial tight junctions and early and selective loss of pericytes, together with increased vascular permeability, capillary occlusions, microaneurysms and, later, loss of endothelial cells. A key role in the evolution of the disease is played by pericytes, specialized contractile mesenchymal cells of mesodermal origin, that, in capillaries, exert a function similar to smooth muscle cells in larger vessels, regulating vascular tone and perfusion pressure. Thickening of the basement membrane, together with systemic and local hypertension, hyperglycaemia, advanced glycation end-product formation and hypoxia, may disrupt the tight link between pericytes and EC causing pericyte apoptosis, while endothelium, deprived of proliferation control, can give rise to new vessels.Pericyte dropout has great consequences on capillary remodelling and may cause the first abnormalities of the diabetic eye which can be observed clinically. Hyperglycaemia and local hypertension are known to be a direct cause of pericyte apoptosis and dropout, and intracellular biochemical pathways of the glucose metabolites have been explored. However, the exact mechanisms are not yet fully understood and need further clarification in order to develop new effective drugs for the prevention of retinopathy.4

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“…Possible mechanistic reasons have been discussed (25,26). Patients with long-standing poor antecedent control, as in our study, may be particularly susceptible.…”

Section: Discussionmentioning

confidence: 99%

Impact of Hypoglycemia Associated With Antihyperglycemic Medications on Vascular Risks in Veterans With Type 2 Diabetes

et al. 2012

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OBJECTIVEHypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.RESEARCH DESIGN AND METHODSPatients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score–matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.RESULTSAmong the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA1c of 10.69 ± 2.61%. The 1-year change in HbA1c was similar (hypoglycemia group −0.51 vs. control group −0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63–2.44]) and microvascular complications (1.76 [1.46–2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10–1.66]).CONCLUSIONSHypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.

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Rapid development and progression of proliferative retinopathy after strict diabetic control.

Cited by 37 publications

References 7 publications

Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine

Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamine

Pericyte Loss in Diabetic Retinopathy: Mechanisms and Consequences

Impact of Hypoglycemia Associated With Antihyperglycemic Medications on Vascular Risks in Veterans With Type 2 Diabetes

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