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

Abstract

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,...

Improved glycemic control induced by both metformin and repaglinide is associated with a reduction in blood levels of 3-deoxyglucosone in nonobese patients with type 2 diabetes

“…Postprandial rise in 3DG (6) and the association between postprandial glucose levels and levels of a-oxoaldehydes including 3DG have been described previously (22). Table 2 First-and second-period baseline values of the studied metabolic variables.…”

“…3DG was measured using liquid chromatographytandem mass spectrometry (LC-tandem MS) (6). After thawing the acidified blood samples, the samples were centrifuged (5 min at 20 000 g) and 80 ml of the supernatant was mixed with 100 ml of the internal standard solution (1 mM/l 2,3-pentanedione dissolved in ethanol).…”

“…The levels of 3DG have been shown to be elevated in patients with diabetes (5,6), particularly in those with diabetic microangiopathy, such as retinopathy (5), neuropathy (5), and nephropathy (5,7).…”

Minimizing Postprandial Oxidative Stress in Type 2 Diabetes: The Role of Exercise and Selected Nutrients

“…Individuals with diabetes and pre-diabetes appear more susceptible to postprandial oxidative stress due to the fact that they experience prolonged periods of hyperglycemia (Ceriello et al, 2002;Y. Miyazaki et al, 2007;Schindhelm et al, 2007) and hypertriglyceridemia (Ceriello et al, 2002;Nappo et al, 2002) following meals, as compared to those with normal blood glucose control. Elevations in both glucose and triglycerides are directly linked to superoxide production (Bae et al, 2001;Nishikawa et al, 2000), a potent RONS which is known to react with other molecules causing additional RONS generation (Brownlee, 2005).…”

“…Individuals who are obese or have metabolic or cardiovascular disease appear to be more susceptible to postprandial oxidative stress, and they typically experience more robust and prolonged periods of hyperglycemia (Y. Miyazaki et al, 2007;Schindhelm et al, 2007;Serin et al, 2007) and hypertriglyceridemia (Ceriello et al, 2002;Nappo et al, 2002) post-feeding, as compared to non-diseased individuals. Again, elevations in blood glucose and triglycerides are directly associated with superoxide production (Bae et al, 2001); hence, a greater increase in either blood glucose or triglyceride post-feeding may be associated with a greater increase in postprandial oxidative stress.…”