Aims/hypothesis: Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction. Methods: In 43 healthy control subjects (age 48.2±1.0 years, mean±SEM) and in 48 untreated agematched subjects with metabolic syndrome (National Cholesterol Education Program's Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique). Results: Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1± 2.6 vs 43.8±2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r= 0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=−0.44, p<0.001), which was impaired in the metabolic syndrome. Conclusions/interpretation: These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.
Diabetic autonomic dysfunction, even when not yet manifest, is associated with a high risk of mortality [1±11] which makes its early identification clinically important. In the early eighties Ewing and co-workers [1,12] validated a battery of laboratory tests for identification of autonomic abnormalities in patients with diabetes mellitus. These tests consist in the measurement of the heart rate changes induced by manouvers such as deep breathing, Valsalva and standing which engage reflexes that alter vagal and sympathetic modulation of the heart [13±17]. They further consist in the measurement of the blood pressure responses to standing, cold pressure test and hand-grip exercise which allow assessment of sympathetic modulation of systemic vascular resistance [15±19].Although useful for the identification of a diabetic-dependent damage of autonomic cardiovascular Diabetologia (1997) Summary Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age ± SD 41.9 ± 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (±71.3 % and ±60.2 % respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (±57.0 % and ±43.5 %, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i. e. under conditions suitable for routine outpatient evaluation. [Diabetologia (1997
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]
We have previously shown that Type I (insulin-dependent) diabetes mellitus is accompanied by a reduced distensibility of the carotid artery, the radial artery and the aorta [1]. We have also shown that this reduction is associated with an increased thickness of the vessel walls and that both changes can be found even in relatively young subjects with no increase in blood pressure and no macrovascular or microvascular complications [1]. This provides evidence that in diabetes there is an alteration of mechanical function and structure which involves both large elastic and middle-size muscle arteries [2±9]. It also provides evidence that this is an early phenomenon of the disease, promoting (1) the remodelling of smaller arteries [10,11] which could facilitate a blood pressure increase, a condition commonly associated with diabe-Progression of large artery structural and functional alterations in Type I diabetes Abstract Aims/hypothesis. Type I (insulin-dependent) diabetes mellitus is accompanied by reduced arterial distensibility and increased arterial wall thickness even in normotensive subjects with no micro-macrovascular complications. It is not known whether, and how fast, these subclinical markers of vascular damage develop over time.Methods. We measured arterial wall distensibility in radial, common carotid artery and abdominal aorta in 60 normotensive patients (aged 35.0 1.2 years, means SE) with Type I diabetes with no microvascular or macrovascular complications and in 20 healthy control subjects matched for age. Arterial distensibility was determined by continuous measurements of arterial diameter through echotracking techniques and by using either the Langewouters (radial artery) or the Reneman formula (carotid artery and aorta). The same echotracking techniques allowed us to ascertain the radial and carotid artery wall thickness. Data were collected before and after 23 1 months.Results. In the first study, carotid artery distensibility was similar but radial artey and aortic distensibility was less (p < 0.01) in patients with diabetes than in control subjects (±39 % and 25 % respectively). This was accompanied by an increase (p < 0.01) in both radial (42 %) and carotid artery wall thickness (46 %). After 23 1 months diabetic subjects showed a further reduction in arterial distensibility (radial±12 %, p < 0.05; carotid±8 %, NS; aorta±20 % p < 0.05) and an increase in arterial wall thickness (radial + 15 %; carotid 14 %, p < 0,05). No change in distensibility and wall thickness values occurred in control subjects. Conclusion/interpretation. The early reduction in arterial distensibility and increase in arterial wall thickness characterizing uncomplicated normotensive Type I diabetes patients shows a measurable worsening over the short term. [Diabetologia (2001) 44: 203±208]
Uncomplicated type I diabetes mellitus is characterized by early structural and functional cardiac alterations. Some of these alterations show a measurable progression within a relatively short time span.
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