T2D-Associated Carotid Plaque Burden and Retinopathy
The deleterious effects of hyperglycaemia are classically separated into microvascular (retinopathy, diabetic nephropathy and neuropathy) and macrovascular complications (coronary artery disease, peripheral arterial disease and cerebrovascular disease).
Traditionally, the micro- and macrovascular complications of diabetes have been viewed, studied, and treated as distinct and independent disorders. However, accumulating data from epidemiological and pathophysiological studies suggest that these vascular complications may share common pathophysiological mechanisms beyond those related to traditional cardiovascular (CV) risk factors. Data obtained from epidemiological studies have clearly demonstrated that diabetic retinopathy (DR), a common chronic microvascular complication of diabetes, is associated with macrovascular disease as well as with increased CV morbidity and mortality in patients with type 2 diabetes mellitus (T2D). In these patients, the presence of DR has been described as an independent risk factor for incident coronary heart disease and ischaemic stroke. Among the possible mechanisms described to explain the interconnection between diabetic micro- and macroangiopathy are metabolic disturbances. Other authors have suggested that microangiopathy of the vasa vasorum (VV), the plexus of microvessels that partially provides oxygen and nutrients to the walls of large arteries, may be involved in diabetic atherosclerosis. Our group recently reported that T2D patients with DR had increased angiogenesis of the VV of the common carotid artery (CCA). These findings were recently confirmed by Sampson et al. in a larger study of T2D patients.
When a clinical CV event occurs, atherosclerotic disease is difficult to reverse. In these cases, ultrasonography of the carotid arteries is frequently used to detect early signs of atherosclerosis, i.e., increased thickness of the arterial wall or the occurrence of plaques. Ample data suggest that plaque and carotid intima-media thickness (cIMT) are associated with prevalent and incident coronary heart disease (CHD) and stroke, with the presence of plaque generally having a stronger association with CVD compared to cIMT alone. Thus, it has recently been demonstrated that ultrasound assessment of a carotid plaque and its total volume or total area progression is a stronger predictor of future CV events than cIMT measurement. A high prevalence (between 43% and 64%) of carotid plaques has been described in T2D patients without evidence of CV disease (CVD). Prospective studies conducted in T2D patients free of any CV event have shown that the percentage of patients with carotid artery plaques is higher in those who develop a CV event compared with those who are free from CV events. Recent epidemiological studies have demonstrated that chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 ml/min, is an independent risk factor for atherosclerotic disease and for the presence of carotid plaques. In T2D patients, a high prevalence of low eGFR without associated albuminuria has been reported and described to be associated with atherosclerosis of peripheral arteries, independently of albuminuria, and with cIMT in several, but not all, studies.
To test the concept that patients with T2D and DR have an increased prevalence of subclinical atherosclerosis, as shown using carotid plaque burden and cIMT measurements, we investigated the association between these measures and retinopathy in a group of patients with T2D but without previous CVD and with normal renal function.
Background
The deleterious effects of hyperglycaemia are classically separated into microvascular (retinopathy, diabetic nephropathy and neuropathy) and macrovascular complications (coronary artery disease, peripheral arterial disease and cerebrovascular disease).
Traditionally, the micro- and macrovascular complications of diabetes have been viewed, studied, and treated as distinct and independent disorders. However, accumulating data from epidemiological and pathophysiological studies suggest that these vascular complications may share common pathophysiological mechanisms beyond those related to traditional cardiovascular (CV) risk factors. Data obtained from epidemiological studies have clearly demonstrated that diabetic retinopathy (DR), a common chronic microvascular complication of diabetes, is associated with macrovascular disease as well as with increased CV morbidity and mortality in patients with type 2 diabetes mellitus (T2D). In these patients, the presence of DR has been described as an independent risk factor for incident coronary heart disease and ischaemic stroke. Among the possible mechanisms described to explain the interconnection between diabetic micro- and macroangiopathy are metabolic disturbances. Other authors have suggested that microangiopathy of the vasa vasorum (VV), the plexus of microvessels that partially provides oxygen and nutrients to the walls of large arteries, may be involved in diabetic atherosclerosis. Our group recently reported that T2D patients with DR had increased angiogenesis of the VV of the common carotid artery (CCA). These findings were recently confirmed by Sampson et al. in a larger study of T2D patients.
When a clinical CV event occurs, atherosclerotic disease is difficult to reverse. In these cases, ultrasonography of the carotid arteries is frequently used to detect early signs of atherosclerosis, i.e., increased thickness of the arterial wall or the occurrence of plaques. Ample data suggest that plaque and carotid intima-media thickness (cIMT) are associated with prevalent and incident coronary heart disease (CHD) and stroke, with the presence of plaque generally having a stronger association with CVD compared to cIMT alone. Thus, it has recently been demonstrated that ultrasound assessment of a carotid plaque and its total volume or total area progression is a stronger predictor of future CV events than cIMT measurement. A high prevalence (between 43% and 64%) of carotid plaques has been described in T2D patients without evidence of CV disease (CVD). Prospective studies conducted in T2D patients free of any CV event have shown that the percentage of patients with carotid artery plaques is higher in those who develop a CV event compared with those who are free from CV events. Recent epidemiological studies have demonstrated that chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) <60 ml/min, is an independent risk factor for atherosclerotic disease and for the presence of carotid plaques. In T2D patients, a high prevalence of low eGFR without associated albuminuria has been reported and described to be associated with atherosclerosis of peripheral arteries, independently of albuminuria, and with cIMT in several, but not all, studies.
To test the concept that patients with T2D and DR have an increased prevalence of subclinical atherosclerosis, as shown using carotid plaque burden and cIMT measurements, we investigated the association between these measures and retinopathy in a group of patients with T2D but without previous CVD and with normal renal function.
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