The Metabolic Syndrome, Circulating Oxidized LDL, and Risk of Myocardial Infarction in Well-Functioning Elderly People in the Health, Aging, and Body Composition Cohort

Holvoet, Paul; Kritchevsky, Stephen B.; Tracy, Russell P.; Mertens, Ann; Rubin, Susan M.; Butler, Javed; Goodpaster, Bret H.; Harris, Tamara B.

doi:10.2337/diabetes.53.4.1068

Cited by 290 publications

(202 citation statements)

References 45 publications

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“…The decrease of ox-LDL by stevioside is particularly important in view of our recent observation that ox-LDL is associated with the metabolic syndrome components obesity, hyperglycemia and insulin resistance, and hyperlipidemia in the general population. 7,8 The decrease in ox-LDL was not due to an increase in PON1 in stevioside-treated mice.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 Moreover, we showed that ox-LDL was associated with the incidence of the metabolic syndrome 6 and with several metabolic syndrome components, especially visceral obesity. 7,8 Stevioside was found to exert antihyperglycemic and insulinotropic effects in a non-obese animal model of type 2 diabetes 9 by acting directly on pancreatic cells. 10 However, its effects on adipose tissue and obesity-associated insulin resistance, inflammation, oxidative stress and atherosclerosis have not been determined.…”

Section: Introductionmentioning

confidence: 99%

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Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

et al. 2009

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Objective: Stevioside is a non-caloric natural sweetener that does not induce a glycemic response, making it attractive as sweetener to diabetics and others on carbohydrate-controlled diets. Obesity is frequently associated with insulin resistance and increased inflammation and oxidative stress. Therefore, we investigated its effects on insulin resistance, inflammation and oxidative stress related to atherosclerosis in obese insulin-resistant mice.Research design: Twelve-week-old mice were treated with stevioside (10 mg kg À1 , n ¼ 14) or placebo (n ¼ 20) for 12 weeks. Results: Stevioside had no effect on weight and triglycerides, but lowered glucose and insulin. Stevioside treatment improved adipose tissue maturation, and increased glucose transport, insulin signaling and antioxidant defense in white visceral adipose tissues. Together, these increases were associated with a twofold increase of adiponectin. In addition, stevioside reduced plaque volume in the aortic arch by decreasing the macrophage, lipid and oxidized low-density lipoprotein (ox-LDL) content of the plaque. The higher smooth muscle cell-to-macrophage ratio was indicative for a more stable plaque phenotype. The decrease in ox-LDL in the plaque was likely due to an increase in the antioxidant defense in the vascular wall, as evidenced by increased Sod1, Sod2 and Sod3. Circulating adiponectin was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the aorta of stevioside-treated mice. Conclusion: Stevioside treatment was associated with improved insulin signaling and antioxidant defense in both the adipose tissue and the vascular wall, leading to inhibition of atherosclerotic plaque development and inducing plaque stabilization.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

et al. 2009

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“…Because a fairly strong correlation between oxidized LDL and LDL cholesterol is a consistent finding in several studies (16,17), we expressed oxidized LDL as a ratio per LDL cholesterol (oxidized LDL-to-LDL cholesterol ratio), as proposed by Holvoet et al (18).…”

Section: Laboratory Analysismentioning

confidence: 99%

Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

Schindhelm¹,

Alssema

Scheffer

et al. 2007

Diabetes Care

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OBJECTIVE -We studied acute changes in markers of glycoxidative and lipoxidative stress, including oxidized LDL, N ε -(carboxyethyl)-lysine (CEL), N ε -(carboxymethyl)-lysine (CML), and 3-deoxyglucosone (3DG), following two consecutive meals. RESEARCH DESIGN AND METHODS -Postmenopausal women (27 with normal glucose metabolism [NGM], 26 with type 2 diabetes) received two consecutive fat-rich meals and two consecutive carbohydrate-rich meals on two occasions. Glucose and triglyceride concentrations were measured at baseline and 1, 2, 4, 6, and 8 h following breakfast; lunch was given at 4 h. Oxidized LDL-to-LDL cholesterol ratio, CEL, CML, and 3DG were measured at baseline and at 8 h.RESULTS -Fasting oxidized LDL-to-LDL cholesterol ratio, 3DG, and CML were higher in women with type 2 diabetes compared with women with NGM and were comparable to the postprandial values at 8 h in NGM. Postprandial rises in the oxidized LDL-to-LDL cholesterol ratio and 3DG were similar in both groups. However, the oxidized LDL-to-LDL cholesterol ratio increased more after the fat-rich meals, whereas CML and 3DG increased more after the carbohydrate-rich meals. After the fat-rich meals, the increase in the oxidized LDL-to-LDL cholesterol ratio correlated with postprandial triglycerides, whereas the increase in 3DG was correlated with postprandial glucose.CONCLUSIONS -The acute changes in markers of glycoxidative and lipoxidative stress in both type 2 diabetes and NGM suggest that postabsorptive oxidative stress may partly underlie the association of postprandial derangements and cardiovascular risk. Diabetes Care 30:1789-1794, 2007P atients with type 2 diabetes have an increased risk of cardiovascular disease (CVD) (1), which can only partly be explained by classical CVD risk factors such as hypertension, high LDL cholesterol, low HDL cholesterol, and smoking (2). In postmenopausal women compared with men, the relative risk of CVD conferred by type 2 diabetes is even higher (3). Zilversmit (4) postulated in 1979 that disturbances in postprandial metabolism may contribute to the excess risk of CVD due to postprandial elevations of glucose and triglyceride-enriched lipoproteins (5,6).Oxidative stress is regarded as a common pathway by which many of the classical CVD risk factors and postprandial dysmetabolism may initiate and promote atherosclerosis (7). Indeed, elevated levels of oxidized LDL are associated with an increased risk for CVD (8). Prolonged exposure to a high-fat diet has been shown to result in an increase in plasma levels of oxidized LDL (9). Another mechanism that might link postprandial dysmetabolism and the risk of CVD in patients with type 2 diabetes includes the formation of advanced glycation end products (AGEs), which are related to micro-and macrovascular complications (10). Two of the most studied AGEs, N ε -(carboxyethyl)lysine (CEL) and N ε -(carboxymethyl)lysine (CML), can be formed on proteins by both glycoxidation and lipid peroxidation pathways. ␣-Dicarbonyl compounds such as 3-deoxyglucosone (3DG), glyoxal,...

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“…Indeed, we have recently shown that the metabolic syndrome in humans is associated with elevated circulating ox-LDL, which predicts the risk for future myocardial infarction. 44 Inflammation plays an important role in atherosclerosis. 45 Adipocytes also contribute to these processes.…”

Section: Oxidative Stress Inflammation and Reduced Atherosclerosismentioning

confidence: 99%

Weight Loss–Associated Induction of Peroxisome Proliferator–Activated Receptor-α and Peroxisome Proliferator–Activated Receptor-γ Correlate With Reduced Atherosclerosis and Improved Cardiovascular Function in Obese Insulin-Resistant Mice

et al. 2004

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Background-Weight loss in obese insulin-resistant but not in insulin-sensitive persons reduces coronary heart disease risk. To what extent changes in gene expression are related to atherosclerosis and cardiovascular function is unknown. Methods and Results-We studied the effect of diet restriction-induced weight loss on gene expression in the adipose tissue, the heart, and the aortic arch and on atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia, and insulin resistance are associated with hypertension, impaired left ventricular function, and accelerated atherosclerosis in those mice. Compared with lean mice, peroxisome proliferator-activated receptors (PPAR)-␣ and PPAR-␥ expression was downregulated in obese double-knockout mice. Diet restriction caused a 45% weight loss, an upregulation of PPAR-␣ and PPAR-␥, and a change in the expression of genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress, and inflammation, most of which are under the transcriptional control of these PPARs. Changes in gene expression were associated with increased insulin sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. PPAR-␣ and PPAR-␥ expression was inversely related to plaque volume and to oxidized LDL content in the plaques. Conclusions-Induction of PPAR-␣ and PPAR-␥ in adipose tissue, heart, and aortic arch is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight loss. Improved lipid metabolism and insulin signaling is associated with decreased tissue deposition of oxidized LDL that increases cardiovascular risk in persons with the metabolic syndrome. Key Words: atherosclerosis Ⅲ circadian rhythm Ⅲ genes Ⅲ lipoproteins Ⅲ obesity I nsulin resistance is now receiving increasing attention not only as a precursor to type 2 diabetes but also as a predictor of increased risk of cardiovascular disease. 1 Fat distributed in the abdominal region is a risk factor for type 2 diabetes and cardiovascular disease and is associated closely with insulin resistance. 2 Weight loss in insulin-resistant but not in insulinsensitive obese persons reduces their risk of coronary heart disease (CHD). 3 It is not known, however, to what extent changes in the intra-abdominal adipose gene expression profile are important for the reduction of the risk. 4 Several adipokines, and more specifically peroxisome proliferator-activated receptors (PPARs), regulate a number of the processes that contribute to the development of atherosclerosis, including dyslipidemia, arterial hypertension, endothelial dysfunction, insulin resistance, and vascular remodeling. Adipokines are preferentially expressed in intraabdominal adipose tissue, and the secretion of proinflammatory adipokines is elevated with increasing adiposity. Approaches to re...

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The Metabolic Syndrome, Circulating Oxidized LDL, and Risk of Myocardial Infarction in Well-Functioning Elderly People in the Health, Aging, and Body Composition Cohort

Cited by 290 publications

References 45 publications

Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

Stevioside inhibits atherosclerosis by improving insulin signaling and antioxidant defense in obese insulin-resistant mice

Fasting and Postprandial Glycoxidative and Lipoxidative Stress Are Increased in Women With Type 2 Diabetes

Weight Loss–Associated Induction of Peroxisome Proliferator–Activated Receptor-α and Peroxisome Proliferator–Activated Receptor-γ Correlate With Reduced Atherosclerosis and Improved Cardiovascular Function in Obese Insulin-Resistant Mice

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