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Endothelial dysfunction represents an early step in the development of atherosclerosis. The purpose of this study was to investigate the relationship between postprandial lipaemia and endothelial dysfunction in patients with overt hypothyroidism (oHT) and subclinical hypothyroidism (sHT). Female subjects with oHT and sHT, as well as female healthy subjects with euthyroid state were enrolled (10 cases in each group). The examination of flow-mediated dilation (FMD) was performed before and after an oral fat-loading by high resolution ultrasound. Endothelial dysfunction after an oral fat challenge was related to the extent of hypertriglyceridemia and free radicals. FMD decreased significantly at 4-h point in 3 groups, (p < 0.05) and then FMD in control and sHT restored to baseline at 8-h point, it was lower than baseline in sHT group at 6-h point (p = 0.042). However, FMD continued to decrease at 6-h point (p < 0.001), and then increased toward to baseline at 8-h point, which was still lower than baseline (p = 0.039) in oHT. Spearman's analysis showed a negative correlation between FMD and triglyceride, a negative correlation between FMD and thiobarbituric acid reactive substances (TBARS), and a positive correlation between triglyceride and TBARS levels during oral lipid-loading test in hypothyroid patients (p < 0.001) and controls (p < 0.05). In hypothyroid subjects including oHT and sHT, even in healthy individuals, FMD was impaired after an oral fat challenge. The endothelial dysfunction observed after an oral fat challenge was related to the extent of hypertriglyceridemia and oxygen-derived free radicals.

Objective: Impaired glucose tolerance (IGT) is considered a transitional phase in the development of type 2 diabetes, and is also independently associated with the occurrence of cardiovascular disease. Endothelial dysfunction (ED) represents a very early step in the development of atherosclerosis. The aim of the present study was to examine ED in the fasting state and after a glucose challenge as well as after administration of an antioxidant agent., Patients and Methods: The study subjects included 42 IGT patients and 26 healthy individuals (control group). The IGT patients were randomly divided into two groups, 21 in each group (the alpha-lipoic acid group and the placebo group). In the alpha-lipoic acid group, 300 mg of alpha-lipoic acid was administrated before an oral glucose tolerance test (OGTT); in the placebo group, 250 ml of 0.9% sodium chloride was administrated before the OGTT. In addition, 250 ml of 0.9% sodium chloride was also administrated to the control subjects before the OGTT (control group), and then vascular function was examined in the fasting state and repeated 1 and 2 h after the glucose load. High-resolution ultrasound was used to measure flow-mediated endothelium-dependent arterial dilation (FMD) and glyceryltrinitrate (GTN)-induced endothelium-independent arterial dilation., Results: In the fasting state, and at 60 and 120 min, FMD in both the placebo and alpha-lipoic acid groups was significantly lower than in the controls (P < 0.01). In the control group, FMD tended to decrease at 60 min after glucose loading and returned to the baseline levels at 120 min (P > 0.05). In the placebo group, FMD decreased significantly at 60 min after glucose loading (P < 0.01) and increased markedly from 60 to 120 min (P < 0.01). The alpha-lipoic acid-treated patients showed FMD values intermediate between the control subjects and the IGT patients treated with placebo, at both 60 and 120 min, and the differences were significant (P < 0.01). In multiple regression analysis, FMD was significantly correlated to fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL-C), lipoprotein (a) [Lp(a)], C-reactive protein (CRP), thiobarbituric acid reactive substances (TBARS) and age in IGT patients at baseline (P < 0.01). Spearman's analysis showed a significant negative correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients (placebo group) (P < 0.01). There was also a significant correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients treated with alpha-lipoic acid (P < 0.05), although the power of association decreased., Conclusion: In subjects with IGT, FMD was impaired both in the fasting state and after a glucose challenge, probably through increased production of oxygen-derived free radicals. The ED observed after a glucose challenge is related to the extent of hyperglycaemia and TBARS, and an antioxidant agent can improve the impairment of endothelial function induced by acute hyperglycaemia.

Osteoprotegerin is a recently identified inhibitor of bone resorption. Recent studies indicate that osteoprotegerin also acts as an important regulatory molecule in the vasculature. The purpose of this study was to investigate the relationship between plasma osteoprotegerin levels and endothelium-dependent arterial dilation in type 2 diabetic patients. The study subjects included 40 newly diagnosed type 2 diabetic patients and 46 healthy subjects. All patients were given insulin therapy for 6 months. Plasma osteoprotegerin concentration was measured in duplicate by a sandwich enzyme-linked immunosorbent assay method, and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual glyceryltrinitrate. The plasma osteoprotegerin level in patients before treatment was 3.36 +/- 0.32 ng/l, which was significantly higher than that in control subjects (2.38 +/- 0.25 ng/l, P < 0.001). After 6 months of treatment, osteoprotegerin levels decreased markedly (2.83 +/- 0.34 ng/l, P < 0.001). Flow-mediated endothelium-dependent arterial dilation in patients before treatment was 3.21 +/- 0.52%, which was significantly lower than that in control subjects (4.46 +/- 0.56%, P < 0.01), and it improved markedly after 6 months of treatment (4.03 +/- 0.49%, P < 0.01). In multivariate analysis, osteoprotegerin was significantly associated with endothelium-dependent arterial dilation, fasting blood glucose (FBG), HbA(1c) (A1C), and ultrasensitive C-reactive protein (CRP) at baseline (P < 0.01). The absolute changes in osteoprotegerin showed significant correlation with changes in endothelium-dependent arterial dilation, FBG, A1C, and CRP in diabetic patients during the course of treatment (P < 0.01). This study shows that plasma osteoprotegerin levels are elevated in newly diagnosed diabetic patients and are significantly associated with endothelial function.