Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

Stehouwer, Coen D. A.

doi:10.2337/dbi17-0044

Cited by 221 publications

(224 citation statements)

References 154 publications

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“…Diabetic retinopathy is associated with systemic vascular complications likely reflecting widespread microvascular disease. 7 More so than in hypertension, retinal venular widening is prevalent in diabetes, correlates with the severity of retinopathy, and predicts progression to overt retinopathy, suggesting a different pathophysiological basis for the change in vessel caliber. 46 Wider venules are seen in response to chronic hypoxia 47 and associate with endothelial dysfunction, 48 suggesting that they reflect microvascular stress in response to metabolic derangement.…”

Section: The Retinal Circulation: Cvd Risk Factors and Outcomesmentioning

confidence: 99%

The eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons

Farrah

Dhillon

Keane

et al. 2020

Kidney International

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Chronic kidney disease (CKD) is common, with hypertension and diabetes mellitus acting as major risk factors for its development. Cardiovascular disease is the leading cause of death worldwide and the most frequent end point of CKD. There is an urgent need for more precise methods to identify patients at risk of CKD and cardiovascular disease. Alterations in microvascular structure and function contribute to the development of hypertension, diabetes, CKD, and their associated cardiovascular disease. Homology between the eye and the kidney suggests that noninvasive imaging of the retinal vessels can detect these microvascular alterations to improve targeting of at-risk patients. Retinal vessel–derived metrics predict incident hypertension, diabetes, CKD, and cardiovascular disease and add to the current renal and cardiovascular risk stratification tools. The advent of optical coherence tomography (OCT) has transformed retinal imaging by capturing the chorioretinal microcirculation and its dependent tissue with near-histological resolution. In hypertension, diabetes, and CKD, OCT has revealed vessel remodeling and chorioretinal thinning. Clinical and preclinical OCT has linked retinal microvascular pathology to circulating and histological markers of injury in the kidney. The advent of OCT angiography allows contrast-free visualization of intraretinal capillary networks to potentially detect early incipient microvascular disease. Combining OCT’s deep imaging with the analytical power of deep learning represents the next frontier in defining what the eye can reveal about the kidney and broader cardiovascular health.

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Section: The Retinal Circulation: Cvd Risk Factors and Outcomesmentioning

confidence: 99%

The eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons

Farrah

Dhillon

Keane

et al. 2020

Kidney International

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“…Type 2 diabetes mellitus (T2DM) accounts for roughly 90% of all individuals with diabetes and the expected increased prevalence directly affects neuropathy, retinopathy, and nephropathy burden, collectively alluded as the classical diabetic microvascular complications [2]. T2DM onset and early progression is a silent process; however, at the time of diagnosis, microcirculatory damage is often present with multiorgan consequences [3,4]. The evolution of diabetic microvascular complications is closely linked with longstanding or uncontrolled disease and may ultimately culminate in severe disabilities, such as diabetic foot ulcers, blindness, and end stage renal disease (ESRD), with increased costs for patients and society [5].…”

Section: Introductionmentioning

confidence: 99%

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

et al. 2020

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Unhealthy dietary habits are major modifiable risk factors for the development of type 2 diabetes mellitus, a metabolic disease with increasing prevalence and serious consequences. Microvascular complications of diabetes, namely diabetic peripheral neuropathy (DPN), retinopathy (DR), and nephropathy (DN), are associated with high morbidity rates and a heavy social and economic burden. Currently, available therapeutic options to counter the evolution of diabetic microvascular complications are clearly insufficient, which strongly recommends further research. Animal models are essential tools to dissect the molecular mechanisms underlying disease progression, to unravel new therapeutic targets, as well as to evaluate the efficacy of new drugs and/or novel therapeutic approaches. However, choosing the best animal model is challenging due to the large number of factors that need to be considered. This is particularly relevant for models induced by dietary modifications, which vary markedly in terms of macronutrient composition. In this article, we revisit the rodent models of diet-induced DPN, DR, and DN, critically comparing the main features of these microvascular complications in humans and the criteria for their diagnosis with the parameters that have been used in preclinical research using rodent models, considering the possible need for factors which can accelerate or aggravate these conditions.

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“…3 The role of vascular endothelial growth factor (VEGF) in the pathophysiology of diabetic retinopathy and DME has been well documented. 2,4 VEGF modulates the development and maintenance of the vasculature, and its expression is upregulated in patients with diabetes, resulting in excessive angiogenesis and increased vascular permeability, including that in the eyes. 2 Intravitreal anti-VEGF therapy has become the standard of care for managing DME due to the favorable benefit-risk profile.…”

Section: Introductionmentioning

confidence: 99%

<p>Intravitreal Aflibercept versus Laser Photocoagulation in Asian Patients with Diabetic Macular Edema: The VIVID-East Study</p>

Chen

Yoon

et al. 2020

OPTH

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The prevalence of diabetes and diabetes-related complications, including diabetic macular edema (DME), is increasing in Asia and worldwide. Methods: VIVID-East was a 12-month, double-masked, randomized, active-controlled, Phase 3 trial (NCT01783886) enrolling adult patients (aged ≥18 years) with DME at 25 centers across China, Hong Kong, Republic of Korea, and Russia. Eyes were randomized 1:1:1 to 2 mg intravitreal aflibercept (IVT-AFL) every 4 weeks (2q4; N=127), 2 mg IVT-AFL every 8 weeks (after 5 initial monthly doses from baseline to week 16) with sham injections on nontreatment visits (2q8; N=127), or macular laser photocoagulation at baseline and sham injections at every visit (laser control group; N=124). The primary efficacy endpoint was mean change in best corrected visual acuity (BCVA) from baseline to week 52. Results: Compared with baseline, at week 52 the mean (SE) BCVA in the 2q4 and 2q8 groups gained +13.6 (0.9) and +13.1 (1.0) letters, respectively, versus −0.5 (1.4) letters in the laser group (P<0.0001 for both). A significantly higher proportion of patients treated with IVT-AFL (2q4 and 2q8) achieved a ≥10-letter or ≥15-letter gain compared with laser (both P<0.0001) (≥10-letter gain: 70.9%, 62.7%, and 23.4%, respectively; ≥15-letter gain: 43.3%, 36.5%, and 12.1%, respectively). Mean reduction in central retinal thickness from baseline to week 52 was significantly greater with IVT-AFL versus laser treatment. Incidence of treatment-emergent adverse events was low and similar across groups; conjunctival hemorrhage (11.8%), retinal hemorrhage (8.7%), retinal aneurysm (7.5%), and retinal exudates (5.5%) being the most frequently reported. Visual and anatomic outcomes in the Chinese subgroup were consistent with the overall population. Conclusion: IVT-AFL treatment resulted in significant visual and anatomic improvements in Asian patients with DME. Treatment benefits observed in the overall study population were mirrored in the subgroup of Chinese patients, who made up the largest population group in the study. Study Registration: NCT01783886.

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Microvascular Dysfunction and Hyperglycemia: A Vicious Cycle With Widespread Consequences

Cited by 221 publications

References 154 publications

The eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons

The eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons

Diet-Induced Rodent Models of Diabetic Peripheral Neuropathy, Retinopathy and Nephropathy

<p>Intravitreal Aflibercept versus Laser Photocoagulation in Asian Patients with Diabetic Macular Edema: The VIVID-East Study</p>

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