Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus

Lockhart, Christopher; McCann, Aaron; Pinnock, Ralph A; Hamilton, Paul; Harbinson, Mark; McVeigh, Gary E.

doi:10.1152/ajpheart.00372.2014

Cited by 8 publications

(6 citation statements)

References 52 publications

(57 reference statements)

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“…Microvascular beds are the sites where the earliest consequences of inflammatory processes occur, leading to endothelial and smooth muscle cell dysfunction, and altered structure and composition of the extracellular matrix. These modifications are recognized as risk factors for the development of atherosclerotic disease in large arteries as well [30]. Also, a rule in diabetic vascular complications has been suggested for advanced glycation end-products assessed by skin autofluorescence [31, 32], HDL dysfunction [33], and altered regulation of extracellular matrix remodeling [34], both in type 1 and type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…Also, a rule in diabetic vascular complications has been suggested for advanced glycation end-products assessed by skin autofluorescence [31, 32], HDL dysfunction [33], and altered regulation of extracellular matrix remodeling [34], both in type 1 and type 2 diabetes. Among microvascular beds, the eye and the kidney are vulnerable target end-organs where functional and structural microvascular alterations anticipate and predict incident CV events [30].…”

Section: Discussionmentioning

confidence: 99%

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Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study

Garofolo

Gualdani

Giannarelli

et al. 2019

Cardiovasc Diabetol

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BackgroundMicrovascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes.MethodsWe recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis.ResultsOut of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59–7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65–15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42–94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88–4.76), 2 MC 1.98 (95% CI 0.75–5.21), 3 MC 7.02 (95% CI 2.44–20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96–5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82–28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59–74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65–3.88), 2 MC 4.33 (95% CI 1.75–10.74), 3 MC 9.31 (95% CI 3.18–27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001).ConclusionsIn type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study

Garofolo

Gualdani

Giannarelli

et al. 2019

Cardiovasc Diabetol

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“…More recently, diabetic patient-based studies have shown that hemodynamic abnormalities occur before the onset of overt retinopathy. For example, quantifiable differences have shown in Doppler flow velocity waveform morphology, as recorded in the retrobulbar circulation, in patients with impaired glucose tolerance and diabetes prior to the development of overt diabetic retinopathy(Lockhart et al, 2014) and significant arteriolar vasoconstriction has been demonstrated which is associated with decreases in total retinal blood flow…”

mentioning

confidence: 99%

The progress in understanding and treatment of diabetic retinopathy

Stitt

Curtis

Chen

et al. 2016

Progress in Retinal and Eye Research

776

657

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“…Kohner suggested that blood flow abnormalities were pathological, and an early biomarker for progression of diabetic retinopathy [93][94][95]. Using more modern techniques, such as Doppler flow velocity waveform analysis, even earlier changes in blood flow have been identified, prior to the onset of clinically overt retinopathy, and even in prediabetic (impaired glucose tolerance) subjects [96]. Decreased total retinal blood flow and arteriolar vasoconstriction have been confirmed by several other groups [97][98][99].…”

Section: Ocular-based Biomarkersmentioning

confidence: 93%

Biomarkers in Diabetic Retinopathy

et al. 2015

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■ AbstractThere is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat diabetic retinopathy, there is need to reliably identify and triage people with diabetes. Biomarkers may facilitate a better understanding of diabetic retinopathy, and contribute to the development of novel treatments and new clinical strategies to prevent vision loss in people with diabetes. This article reviews key aspects related to biomarker research, and focuses on some specific biomarkers relevant to diabetic retinopathy.

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Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus

Cited by 8 publications

References 52 publications

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study

The progress in understanding and treatment of diabetic retinopathy

Biomarkers in Diabetic Retinopathy

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