Plasma levels of endothelin, lipid peroxides and prostacyclin in diabetic patients with macroangiopathy.

The prevalence of macroangiopathy is increased in diabetes mellitus. Endothelial cell injury is thought to be an early event leading to atherosclerosis which may be initiated by several factors. We have investigated the relationship between plasma endothelin, lipid peroxide (measured as thiobarbituric acid reacting species (TBARS)) and 6-keto-prostaglandin-F1A (6-keto-PG-F1A) in Type 2 diabetic patients with macroangiopathy. Fifty-three diabetic subjects with macroangiopathy were investigated, together with 50 diabetic and 50 control subjects without evidence of vascular disease. Both the endothelin and TBARS levels were significantly higher in diabetic patients with macroangiopathy (10.8 (8.0-14.4) pmol/l and 5.6 (3.2-9.7) micromol/l, respectively) compared with control subjects (7.6 (5.0-11.0) pmol/l and 4.5 (3.0-6.4) micromol/l, P<0.001) and with diabetic subjects without macroangiopathy (7.4 (4.9-11.2) pmol/l (P<0.001) and 4.9 (3.0-8.0) micromol/l (P<0.05)). 6-Keto-PG-F1A levels were significantly decreased in diabetic subjects with macroangiopathy 209 (123-355) pg/ml than in normal subjects 241 (137-425) pg/ml, (P<0.05) and diabetic subjects without macroangiopathy 224 (162-309) pg/ml, (P<0.05). Comparison of levels of endothelin with those of TBARS in macroangiopathy group, showed that endothelin is a more consistent marker of the atherogenic process (P<0.01). In conclusion, we have shown that there are abnormalities of endothelium-derived factors in diabetic patients with macroangiopathy, mainly in endothelin. Furthermore, in this group there was a positive correlation between endothelin and fasting insulin levels.

[Myocardial perfusion scintigraphy using 99mTC-tetrofosmin: a comparison with coronary angiography]. / Myokard-Perfusionsszintigraphie mit 99mTc-Tetrofosmin: Ein Vergleich mit der koronaren Angiographie.

AIM: Coronary angiography is still the most reliable method for the detection of coronary artery disease. In this study we compared to this method the accuracy of 99mTc-Tetrofosmin myocardial SPECT. METHOD: Fifty two patients (38 male and 14 female) were studied with stress-rest 99mTc-Tetrofosmin myocardial SPECT. Two independent observers evaluated the uptake of the radiotracer using a score from 0 to 4. All patients underwent coronary angiography and the results were compared to SPECT findings. We considered as hemodynamic significant any obstruction greater than 50% and as ischemic any myocardial region with radiotracer uptake less than 4 at stress. RESULTS: There was good segmental correspondence between tetrofosmin scintigram and angiography. Sensitivity 72.2-91.1%, specificity 80.0-88.2%, ppv 76.4-88.5% and npv 83.3-85.7%, depending on the obstructed vessel. CONCLUSION: 99mTc-Tetrofosmin myocardial SPECT is a reliable alternative for the detection of CAD.

Carotid atherosclerosis in type 2 diabetes mellitus: potential role of endothelin-1, lipoperoxides, and prostacyclin.

Factors were studied that may initiate macroangiopathy or enhance or aggravate its pathogenesis in patients with type 2 diabetes mellitus. A total of 151 diabetics were compared with healthy controls (n=50); all patients and subjects were normotensive and without renal failure. Plasma endothelin-1 and free radical levels were measured. In addition, plasma prostacyclin levels were assessed by assaying its stable, spontaneous, breakdown product 6-keto-prostaglandin-F1a. Diabetics were divided into three groups: those with clinically evident macroangiopathy and those with early or without atherosclerosis (as determined by the carotid intima-media thickness. Plasma endothelin-1 levels were increased in all diabetics with atherosclerosis. Plasma free radical levels were increased in diabetics with macroangiopathy when compared with control subjects. The plasma levels of 6-keto-prostaglandin-F1a were slightly, but significantly, decreased in the diabetics with macroangiopathy when compared with control subjects. The carotid intima-media thickness was significantly greater in diabetics without macroangiopathy when compared with the controls. Furthermore, the intima-media thickness increased significantly in this group of diabetics but not in the controls over a 30-month follow-up period. Several factors may contribute to atherogenesis in diabetics. These include increased plasma endothelin-1 and free radical levels as well as a deficiency of prostacyclin. These factors may become targets for intervention as well as markers of disease progression.

Tc-99m tetrofosmin myocardial perfusion imaging before and six months after percutaneous transluminal coronary angioplasty.

The role of Tc-99m tetrofosmin single-photon emission tomography (SPECT) in the evaluation of myocardial perfusion before and 6 months after successful percutaneous transluminal coronary angioplasty (PTCA) was assessed in 41 consecutive patients (32 men and 9 women). Twenty-five patients had one-vessel disease, 14 had two-vessel disease, and 2 had three-vessel disease. Thirty-six patients had dilation of one vessel and five patients dilation of two stenosed vessels, with a total of 46 dilated vessels. All patients underwent coronary angiography both before PTCA and 6 months after revascularization. Restenosis was angiographically demonstrated in 16 (39%) patients and 16 (34.8%) vessels. Tc-99m tetrofosmin myocardial SPECT was 81.3% sensitive and 88% specific for the detection of restenosis in the group of patients with a positive predictive value of 81.3% and a negative predictive value of 88%. Sensitivity, specificity, positive predictive value, and negative predictive value were 81.3%, 90%, 76.5%, and 89.7%, respectively, for restenosis detection in specific vessels. It was concluded that most patients who underwent successful PTCA (34 of 41, or 82.9%) had significant (P < 0.001) improvement in their scan image 6 months after the angioplasty, and that Tc-99m tetrofosmin myocardial SPECT is an excellent tool to follow these patients because it can detect restenosis accurately and noninvasively.

Plasma levels of endothelin and early carotid atherosclerosis in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since plasma endothelin concentrations were released from vascular endothelial cells, we have investigated the possible relationship between endothelin 1 (ET-1) and arterial wall thickness. Ninety-eight patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 50 non-diabetic subjects were studied. After an overnight fast, blood was taken for ET-1, glucose, HbA1c, lipids, insulin and C-peptide. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by B-mode ultrasound. ET-1 levels were significantly elevated in diabetic patients with IMT>1100 microm, 8.3 pmol/l (5.2-12.9) compared with control subjects, 7.6 pmol/l (5.0-11.0), p<0.01 and with diabetic subjects with IMT<500 microm, 7.43 pmol/l (4.8-11.1), p<0.01. The diabetic (IMT>1100 microm) study group had also significantly higher levels of insulin, 102.8 +/- 46.4 pmol/l vs control subjects, 77.5 +/- 32.4 pmol/l, p<0.01. In diabetic subjects, no correlation was found between ET-1 and IMT with glucose, HbA1c, lipids, age or duration of diabetes, respectively. We conclude that ET-1 levels are elevated in Type 2 diabetic patients with increased IMT. Thus providing further support for the role of endothelin in atherosclerosis.

Progression of carotid atherosclerosis and the role of endothelin in diabetic patients.

An increased thickness of the carotid artery wall is thought to be a sign of early atherosclerosis. Since vascular endothelium is the site of formation of several substances, we have investigated the rate of progression of carotid atherosclerosis and the contribution of endothelin (ET-1), lipid peroxides [measured as thiobarbituric acid reacting species (TBARS)] and 6-keto-Prostaglandin-F1A (6-keto-PG-F1A) at baseline and after 30-months. Fifty patients with Type 2 diabetes without evidence of macroangiopathy, hypertension, proteinuria or proliferative retinopathy, and 27 healthy, non-diabetic persons were studied. Arterial wall thickness was measured as the mean of the maximum intimal-medial thickness (IMT) in 16 carotid segments by b-mode ultrasound. The IMT values was significantly increased in diabetic subjects (at baseline: 1110 +/- 310 microm, after 30 months: 1260 +/- 280 microm, p < 0.01), but not in control subjects (1100 +/- 280 microm, 1200 +/- 290 microm, respectively). At baseline time both groups had similar levels of ET-1, TBARS and 6-keto-PG-F1A. In 30-months follow-up, the ET-1 level 8.0 pmol/l (5.8-10.7) was significantly elevated in diabetic subjects, compared with the level at baseline time 7.43 pmol/l (4.8-11.1) p < 0.01. No significant differences were found in the other examined parameters in the studied groups. Although insulin levels remained unchanged in the two studied groups, in 30 months follow-up, the insulin level in the diabetic subjects, 92.4 +/- 35.1 pmol/l was significantly elevated compared with those of control subjects 76.0 +/- 31.0 pmol/l, p < 0.05. In conclusion, endothelis is the main associate of the change of IMT value over 30 months in diabetic patients, in whom the extent of atherosclerosis was significantly greater than in control subjects.