**3. Glucose-associated oxidative stress and inflammation**

Exposure to elevated plasma glucose in patients with type 2 diabetes mellitus is associated with both an increased level of ROS and a drop in cell antioxidant defense, enzymatic as well as non-enzymatic [4, 5]. In addition to serving as a barrier to control movements of fluid, solutes and cells between blood and tissue, the endothelial layer also play a key role in regulating vascular tone and inflammatory processes [40]. While the impact of hyperglycemia on endothelial cell metabolism is beyond the scope of this presentation it should be noted that, at normal fasting plasma glucose concentrations (4–6 mM, 72–108 mg/dL), the glucose transporter GLUT-1 is already functioning at saturation level [41]. GLUT-1 is the primary glucose carrier responsible for the uptake of glucose by endothelial cells [42]. In vitro studies with human umbilical vein endothelial cells have indicated that exposure to high concentration of glucose is associated with increased oxidative stress as assessed by increased levels of nitrotyrosine and 8-hydroxy-2′-deoxyguanosine [6]. In fact, the increase in oxidative stress was even more pronounced when endothelial cells were exposed intermittently to high and low glucose concentrations [6]. It has also been demonstrated that high

glucose levels stimulate ROS production through protein kinase C (PKC)-dependent activation of NAD(P)H oxidase [43, 44]. The net result of constant and intermittent hyperglycemia is enhancement of endothelial cell apoptosis [6, 44].

In both normal and type 2 diabetic patients, intermittent hyperglycemia has been demonstrated to be more deleterious to endothelial cell metabolism and oxidative stress than constant elevations in plasma glucose [45]. In fact, reduction in the mean amplitude of glycemic excursion with dipeptidyl peptidase-IV inhibition in patients with type 2 diabetes is associated with reduction in oxidative stress and biomarkers of inflammation [46].

In addition to the stimulation of ROS production, exposure to high glucose concentrations can also lead to nonenzymatic modifications of proteins with the formation of glycated proteins or advanced glycation end-products (AGE) [47]. Glycation of specific proteins can severely alter their function as in the case of glycated hemoglobin C with increased affinity for oxygen and subsequent decreased oxygen delivery to tissues [48]. Glycation of plasma LDL by methylglyoxal, a side product of glycolysis, results in enhanced delivery of these pro-atherogenic particles to the arterial wall leading to increased risk for atherosclerosis in patients with type 2 diabetes [49]. Glycation of insulin has also been suggested to contribute to insulin resistance leading to more severe hyperglycemia [50].

### **4. Meal-induced oxidative stress and inflammation**

The fat content of a typical Western meal ranges from 20 to 40 g of fat which corresponds to between 5 and 8 times the total pool of TG in plasma. In a healthy individual with normal metabolism, plasma TG level reaches peak level by 2 h after meal and returns to pre-meal level by 6 h. As many individuals customarily consume 3 meals a day, they spend the majority of their day in the postprandial state. Several processes contribute to the increased oxidative stress and inflammatory state associated with meal consumption [51]. The magnitude and timing of postprandial inflammatory response to a high-fat meal may depend on fat content, caloric intake, body-mass index [52] as well as age of the individual [53, 54].

Firstly, as noted in earlier section, the intermittent secretion of intestinal chylomicrons after each meal has a direct effect on the metabolism of circulating hepatic VLDL. While this may not be the case for individuals with normal TG levels, the lipolytic system may be saturated in individuals with elevated TG as in the case of obesity and diabetes. The net result is a delayed clearance of TG-rich lipoproteins, prolonged interactions of TG-rich particles with the endothelium, and greater potential for the transfer of ROS from the arterial wall to circulating plasma lipoproteins (**Figure 1B**). Treatment of peripheral blood mononuclear cells with lipolysis products of postprandial TG-rich lipoproteins resulted in increased expression of TNFa, IL-1b, and IL-8 [55].

Secondly, the meal-induced change in free fatty acids can contribute to the deleterious impact on the endothelium not only with respect to the increased in concentrations but also to the type of free fatty acids. In patients with insulin resistance, the impact of postprandial free fatty acids is further exacerbated by the failure of postprandial insulin to inhibit the activity of hormone-sensitive lipase (HSL) in tissues. In the normal individuals, the increase in insulin concentration during postprandial lipemia would inhibit the activity of HSL and shut off the mobilization of free fatty acids from peripheral tissues [56–58]. With insulin resistance, HSL remains active during postprandial lipemia and continues to mobilize free fatty acids from intracellular stores contributing to even higher plasma free fatty acid concentrations.

**111**

*Postprandial Triglycerides, Oxidative Stress, and Inflammation*

were also reduced [60] with the addition of prandial insulin.

impact on the time course of postprandial response [63].

AGE advanced glycated end-products

HDL high-density lipoproteins

LDL low-density lipoproteins LPL lipoprotein lipase HSL hormone sensitive lipase ROS reactive oxygen species

TRL TG-rich lipoproteins

VLDL very-low density lipoproteins

CRP (hs-CRP) high-sensitive C-reactive protein

Thirdly and most importantly is the independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on oxidative stress and inflammation [10]. In both normal and diabetic individuals, compared to high fat meal, the inclusion of a glucose dose equivalent to an oral glucose tolerance test resulted in greater increase in nitrotyrosine and circulating adhesion molecules, including E-selectin, ICAM-1, and VCAM-1 [59]. Management with simvastatin in the short term (3 days) did not affect lipids but reduced the effect on nitrotyrosine and adhesion molecules. Extended therapy with simvastatin (3 months) blunted the meal-induced hypertriglyceridemia as well as the post-prandial responses in nitrotyrosine and adhesion molecules [10, 59]. In patients with type 2 diabetes, meal-induced increases in TG and glucose were attenuated by prandial + basal insulin [60]. Post-meal increased in C-reactive protein (hs-CRP), IL-6, and TNFa

In view of the fact that individuals are in a postprandial state throughout the day, assessment of oxidative and inflammatory status in the fasted might not provide an accurate snapshot. It is important to understand the processes that affect oxidative stress and inflammatory status in a non-fasted state [61]. Additional research is needed to understand how nutrients, with respect to quality, quantity, and frequency, could be managed to attenuate the deleterious effect of postprandial hypertriglyceridemia and hyperglycemia on oxidative stress and inflammation [62]. Blunting the acute daily fluctuations in plasma glucose and triglycerides may be a novel mode of management to reduce oxidative stress and inflammation in highrisk individuals. Furthermore, special attention should be placed on the timing of antioxidant ingestion in relation to meal consumption as that might have a direct

Assessment of oxidative and inflammatory status in the fasted state may not provide an accurate picture of the metabolic status of an individual. Intermittent elevations in plasma triglycerides and glucose associated with meal consumption throughout the day may be associated with considerable increase in oxidative stress

and inflammation depending on the quantity and quality of the meals.

*DOI: http://dx.doi.org/10.5772/intechopen.91303*

**5. Future directions**

**6. Conclusions**

**Abbreviations**

FFA free fatty acid

IL interleukin

TG triglycerides

*Postprandial Triglycerides, Oxidative Stress, and Inflammation DOI: http://dx.doi.org/10.5772/intechopen.91303*

Thirdly and most importantly is the independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on oxidative stress and inflammation [10]. In both normal and diabetic individuals, compared to high fat meal, the inclusion of a glucose dose equivalent to an oral glucose tolerance test resulted in greater increase in nitrotyrosine and circulating adhesion molecules, including E-selectin, ICAM-1, and VCAM-1 [59]. Management with simvastatin in the short term (3 days) did not affect lipids but reduced the effect on nitrotyrosine and adhesion molecules. Extended therapy with simvastatin (3 months) blunted the meal-induced hypertriglyceridemia as well as the post-prandial responses in nitrotyrosine and adhesion molecules [10, 59]. In patients with type 2 diabetes, meal-induced increases in TG and glucose were attenuated by prandial + basal insulin [60]. Post-meal increased in C-reactive protein (hs-CRP), IL-6, and TNFa were also reduced [60] with the addition of prandial insulin.
