Early impairment of large artery structure and function in Type I diabetes mellitus

Abstract

Diabetes mellitus is associated with an increased risk of atherosclerosis [1]. Atherosclerosis is responsible for the increased rate of coronary heart disease, cerebrovascular disease and peripheral artery disease typical of diabetes mellitus [2±13]. It is not, however, well established how early alterations in large artery function, that may preceed the appearance and favour the progression of atherosclerotic lesions, i. e. a reduced arterial distensibility, occur in diabetic patients [14±16]. This is because most studies on arterial distensibility have been done in Type II (non-insulindependent) diabetes mellitus, where it is difficult to separate the arterial stiffening due to abnormalities Diabetologia (1999) Abstract Aims/hypothesis. Diabetes mellitus is associated with an increased incidence of atherosclerosis. How early functional and structural alterations of large arteries that may preceed atherosclerosis occur in the course of this disease has, however, never been conclusively documented. Methods. We evaluated arterial wall distensibility in the radial artery, common carotid artery and abdominal aorta in 133 patients (aged 35.4 ± 0.9 years, means ± SEM) with Type I (insulin-dependent) diabetes mellitus and no macrovascular complications. Arterial distensibility was derived from continuous measurements of arterial diameter through echotracking techniques and use of either the Langewouters (radial artery) or the Reneman (carotid artery and aorta) formula. The same echotracking techniques enabled us to obtain radial artery and carotid artery wall thickness. Data were compared with those from 70 age-matched normotensive control subjects. Results. In diabetic patients arterial distensibility was consistently less (p < 0.01) than in control subjects, the reduction averaging 26 %, 14 % and 25 % for the radial artery, carotid artery and aorta, respectively. This was accompanied by an increase (p < 0.01) in both radial and carotid artery wall thickness. The changes were more pronounced in patients with microalbuminuria, retinopathy or neuropathy or both. They were evident also in those without microvascular complications. This was the case also when subjects in whom diabetes was associated with hypertension (n = 30) were excluded from data analysis. Carotid and aortic wall abnormalities showed a relation with the duration of disease and blood pressure whereas radial artery abnormalities showed a relation with glycated haemoglobin. Conclusion/interpretation. Type I diabetes is characterised by diffuse arterial wall stiffening and thickening which progress with the severity of the disease but can clearly be seen also in the absence of any diabetic-related complication. This suggests that in diabetes stiffening and thickening are an early marker of vascular damage. [Diabetologia (1999) 42: 987± 994]

Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus

“…4,5 Peripheral muscular arteries have been less well studied: results are variable, showing either unchanged brachial artery or increased radial artery stiffness in type 1 diabetes patients of mixed gender 21,22 or unchanged femoral artery stiffness in both males and females. 23 The behaviour of the brachial artery wall is of specific interest since it is often used as a model artery in the study of the endothelium, where dysfunction is suggested to precede atherogenesis.…”

Autonomic nervous function, arterial stiffness and blood pressure in patients with Type I diabetes mellitus and normal urinary albumin excretion

“…28 On the other hand, cross-sectional studies in DM-1 suggest that impaired autonomic nervous function occurs considerably earlier than, and therefore may contribute to, increased arterial stiffness. 6,7,9,10 Clearly, prospective studies are required to resolve this issue.…”

“…Previous studies have addressed some combinations of early changes, 8,10,13,14 but not extensively. We hypothesized that incipient neuropathy could influence large artery stiffness by direct effects on large arteries (through effects on tone, on proliferation of smooth muscle cells, and on extracellular matrix composition), as well as by effects on small arteries and arterioles, which might alter pulse wave reflection.…”

Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment?

“…Pulse pressure increases with age as a result of arterial stiffening. As compared with age-matched, non-diabetic controls, patients with type 1 diabetes have stiffer arteries, and the process of arterial stiffening is initiated before any signs of microvascular or macrovascular disease can be detected [61]. The increase in stiffness is correlated with duration of disease, independently of age [62], and this may be of particular importance in childhood-onset diabetes.…”