HORMONES 2016, 15(3):321-344
DOI: 10.14310/horm.2002.1697
Postprandial dysmetabolism: Too early or too late?
Christos Pappas,1 Eleni A. Kandaraki,2 Sofia Tsirona,1 Dimitrios Kountouras,3 Georgia Kassi,2 Evanthia Diamanti-Kandarakis1

1Department of Endocrinology and Diabetes Center of Excellence, EUROCLINIC, Athens, Greece; 2Endocrine Unit 3rd Department of Medicine University of Athens Medical School, Athens, Greece; 3Department of Medicine Hepatology Unit, Hygeia Hospital, Athens, Greece


Postprandial dysmetabolism is a postprandial state characterized by abnormal metabolism of glucose and lipids and, more specifically, of elevated levels of glucose and triglyceride (TG) containing lipoproteins. Since there is evidence that postprandial dysmetabolism is associated with increased cardiovascular mortality and morbidity, due to macro- and microvascular complications, as well as with conditions such as polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD), it is recommended that clinicians be alert for early detection and management of this condition. Management consists of a holistic approach including dietary modification, exercise and use of hypoglycemic and hypolipidemic medication aiming to decrease the postprandial values of circulating glucose and triglycerides. This review aims to explain glucose and lipid homeostasis and the impact of postprandial dysmetabolism on the cardiovascular system as well as to offer suggestions with regard to the therapeutic approach for this entity. However, more trials are required to prevent or reverse early and not too late the actual tissue damage due to postprandial dysmetabolism.


Dysmetabolism, Dysglycemia, Dyslipidemia, Insulin resistance, PCOS, Steatohepatitis

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Postprandial dysmetabolism comprises a new parameter for the assessment of carbohydrates and lipids homeostasis. While the conventional risk factors defining cardiovascular disease are evaluated in a fasting state, postprandial dysmetabolism is a postprandial state distinguished by abnormally increased circulating levels of glucose and lipids and therefore constitutes an independent risk factor for the onset of cardiovascular events.1 In this review we will focus specifically on a) mechanisms that disturb the postprandial homeostasis of glucose and lipids, b) the impact of the impaired metabolism of these nourishing substrates on cardiovascular disease and c) therapeutic interventions aimed at correcting postprandial dysmetabolism.


Homeostasis of glucose metabolism: Postprandial glucose metabolism is regulated by the action of hormones, such as insulin, glucagon, amylin and the incretin hormones, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic peptide (GIP).2 (Figure 1).

Figure 1. Postprandial plasma glucose homeostasis.

Insulin is produced by the beta cells of the pancreas as proinsulin before being secreted and is subsequently cleaved into insulin and C-peptide. During a meal insulin is secreted in two phases: the first consists of a rapid short-term rise which lasts a few minutes and the second of a more progressive release proportional to the glycemic load of the meal.1,3 Data suggest that an impaired first phase of insulin secretion is an indicator of beta cell dysfunction encountered in patients with early diabetes and prediabetes.1,2,4-6 The effect of insulin on glucose homeostasis is to reduce the postprandial glucose levels, a goal that is achieved via three actions. a) It increases the glucose uptake by peripheral tissues, mainly by skeletal muscles. This action is mediated mainly through an isoform of a family of glucose transporters proteins, GLUT4. The GLUT4 protein transporter is a major regulator of whole-body glucose homeostasis and its recruitment to the cell surfaces of muscle and adipose cells is stimulated by insulin.7 b) It promotes glycogen synthesis. c) It inhibits glucagon secretion, thus resulting in reduced glucose production by the liver.2

Glucagon is secreted from alpha pancreatic cells into the portal vein and promotes hepatic glucose production during fasting via glucogenolysis and gluconeogenesis.2,8 After food consumption glucagon secretion is suppressed by insulin, amylin and GLP1. Glucagon plays a significant role in postprandial hyperglycemia. In diabetic patients the suppression of glucagon secretion is not adequate, leading to hyperglucagonemia and subsequent increased glucose production by the liver.9

Amylin (also known as islet amyloid polypeptide-IAPP) is synthesized by beta pancreatic cells and released with insulin in response to the same stimulus. Amylin contributes to maintaining glucose homeostasis by delaying gastric emptying, suppressing glucagon release and controlling satiety.2,10 In diet-induced obese rats, amylin reduced their body weight and body fat with relative preservation of lean tissue.11

The GLP1 and GIP are peptides secreted from intestinal cells during nutrient ingestion. GLP1 is produced by L cells which are located primarily in the ileum but also in the colon, while GIP is produced by K cells which are located in the proximal parts of the small intestine.12 The incretin effect refers to the amplification of insulin secretion that is observed when glucose is taken orally, as opposed to being infused intravenously, to provide identical plasma glucose concentrations.13 Incretin hormones act directly on the pancreas stimulating insulin secretion by beta cells in a glucose-dependent manner. In addition, GLP1 inhibits glucagon secretion by pancreatic cells and delays gastric emptying. The latter defines the main mechanism contributing to reducing postprandial overproduction of glucose. Furthermore, animal and in vitro studies have shown that it enhances beta cell proliferation and differentiation and seems to inhibit apoptosis.12,15 After their release, incretin hormones are rapidly broken down in the circulation by dipeptylpeptidase-4 inhibitor enzyme (DDP-4).2,14

While it is known that the incretin effect is reduced in patients with type 2 diabetes,13,16 there has been debate as to whether the impairment of the incretin effect is due to reduced secretion of GIP and GLP1. Recent data indicate that reduced incretin secretion per se is not the factor responsible for the diminished stimulation of insulin secretion seen in type 2 diabetes;16-19 moreover, it appears that in type 2 diabetes, GIP no longer modulates glucose-dependent insulin secretion even at pharmacological plasma levels.19 A meta-analysis of 688 participants (363 patients with type 2 diabetes vs 325 non-diabetic controls) demonstrated that patients with type 2 diabetes are in general characterized by preserved GIP secretion in response to oral glucose and meal tests. However, post hoc subgroup analyses showed that high BMI, younger age and low HbA1c level seem to positively affect the GIP responses in diabetic patients.16 Another meta-analysis evaluating the secretion of GLP1 in 554 participants (275 patients with type 2 diabetes and 279 non-diabetic controls) suggested that diabetic patients in general do not exhibit reduced GLP1 secretion in response to an oral glucose tolerance test (OGTT) or meal test.17 However, meta-regression analyses exhibited independent effects of HbA1c and fasting plasma glucose levels on GLP1 iAUC responses and, moreover, a post hoc subgroup analysis showed that increasing levels of HbA1c associated negatively with GLP1 iAUC.17 The latter observations may explain the conflicting results from other studies which included older patients with a long history of diabetes and relatively high HbAic and fasting plasma glucose levels, thus implying that the GLP1 secretion profile may be preserved in the early stages of diabetes and subsequently alter during the progression of diabetes.17 Xu et al studied the expression of GIP and GLP1 beta cell receptors in hyperglycemic rats and found that they were significantly decreased in 90% of pancreatectomized rats. Sub-expression was reversible when glucose levels were normalized.18 This verification indicates that downregulation of pancreatic incretins receptors due to chronic hyperglycemia may be an important determinant of a reduced incretin effect in diabetic patients.

GLP2 is another proglucagon-derived peptide produced by a subset of enteroendocrine cells within the epithelium of the small and large intestine and by a population of neurons in the brainstem.20 GLP2 increases absorption of nutrients, while it has been shown that parenteral infusion in non-obese humans increases glucagon secretion.21 However, though it was once considered to have no effect on insulin secretion,22 recent data from animal model experiments indicate that GLP2 may promote insulin sensitivity, particularly in conditions associated with obesity.20 Although the underlying mechanisms have yet to be determined, some possible actions include food intake reduction mediated by the central nervous system, neuroendocrine signals which suppress hepatic glucose production and reduced gut permeability with subsequent bacterial-endotoxemia.20 Nevertheless, results from human studies still remain inconsistent and future research is needed.20

Homeostasis of lipid metabolism: The role of lipids in postprandial dysmetabolism is important. Postprandial dysmetabolism is mainly characterized by elevated levels of triglycerides (TG) and their remnant lipoprotein particles (RLPs),1 therefore a brief overview of TG metabolism and homeostasis is essential (Figure 2).

Figure 2. Triglycerides plasma homeostasis. TG: triglycerides, PL: pancreatic lipase, FFA: free fatty acid, MG: monoglycerides, TAG: triacyloglyceroles, CHM: chylomicrons, LPL: lipoprotein lipase, RLPs: remnants lipoprotein particles, VLDL: very low density lipoproteins, GPIHBP1: Glycosylphosphatidylinositol-anchored high density lipoprotein 1, GLP1: glucagon-like peptide 1, GLP2: glucagon-like peptide 2.

After the consumption of a meal containing lipids, dietary origin triglycerides are hydrolyzed in the intestine to free fatty acids and monoglycerides by the enzyme pancreatic lipase Subsequently, they are absorbed by intestinal epithelial cells, converted to triacylglyceroles and packed with ApoB48 into chylomicrons, which are then secreted in the lymphatic circulation.23-25

Very low density lipoproteins (VLDL) are produced and secreted by the liver and contain triglycerides packed with ApoB100. They are initially synthesized in the hepatic endoplasmatic reticulum as pre-VLDL and subsequently form VLDL2. In the Golgi apparatus VLDL2 may then be converted to larger VLDL1 by the addition of lipids.24 Large VLDL particles are considered to be more atherogenic as they are associated with endothelial dysfunction and the formation of foam cells in vessel walls.24

Chylomicrons and VLDL break down by several lipases (lipoprotein lipase-LPL, hepatic lipase) into fatty acids and RLPs and compete in clearance.23-25 LPL is located in capillary endothelial cells, mainly in the heart, adipose tissue and skeletal muscle.26,27

Lipolysis is a catabolic pathway which occurs mainly in adipose tissue and is characterized by the hydrolysis of TG into fatty acids and glycerol which are subsequently released into the circulation, providing peripheral tissues with the necessary energy demands.28 Lipogenesis, on the other hand, is an anabolic pathway which occurs principally in adipose tissue, but also in other organs such as the liver, muscle, heart and pancreas. It leads to TG production through free fatty acid esterification and is distinguished from lipogenesis originating from free fatty acids derived from the diet and de novo lipogenesis which occurs principally in the liver and mainly after a high carbohydrate meal.28 Insulin plays a critical role in the regulation of lipid homeostasis and is implicated in the subtle balance between lipolysis and lipogenesis, since it stimulates lipid synthesis and adipogenesis and inhibits lipolysis.28

Apart from insulin action on lipid metabolism, it seems that gut peptides like GLP1 and GLP2 may also play an important role in lipid homeostasis affecting postprandial hypertriglyceridemia. It has been reported that GLP1 ameliorates postprandial hyperlipidemia via several mechanisms, including reduction of intestinal lymph flow, TG absorption, gastric emptying and gut motility and decreased intestinal lipoprotein production and secretion.25 It has also been noted in experimental animal models that administration of GLP1 analogs may result in reduced VLDL production by the liver and decreased expression of genes involved in hepatic de novo lipogenesis.29 On the other hand, GLP2 appears to be associated with high postprandial TG, ApoB48 and free fatty acids concentrations, probably via enhancement of intestinal lipid absorption and intestinal lipoprotein particles release.30

Τhe risk factors which seem to contribute to postprandial hypertriglyceridemia are obesity, insulin resistance, VLDL hypersecretion, reduced lipolysis by LPL, reduced RLPs clearance by hepatic receptors and genetic factors.

It has been found that obese individuals, and especially those exhibiting visceral obesity, develop increased response in postprandial TG after the consumption of a fatty meal compared to non-obese subjects.31,32 Meanwhile, it has been proposed that elevated adiposity results in a high flow of free fatty acids to the liver, leading to increased hepatic TG synthesis.23 Hepatic free fatty acid delivery is also increased in humans with insulin resistance resulting in excess secretion of VLDL.23,33 In fact, obesity and insulin resistance are closely associated, leading to dysregulation of TG homeostasis. During adipose tissue expansion, adipocytes become hyperplastic and dysfunctional and subsequently resistant to the antilipolytic effect of insulin.28 As subjects’ resistance increases, plasma free fatty acid levels also rise: the resulting excess free fatty acid release is toxic for many tissues and leads to reduced glucose uptake by liver and muscle, pancreatic beta cell dysfunction and stimulation of hepatic TG synthesis and VLDL production.28 Blackburn et al. compared post-challenge triglyceride (TG)-rich lipoprotein (TRL) levels after a high fat content breakfast in men with impaired glucose tolerance (IGT) versus men with normal glucose tolerance (NGT): the results showed that men with IGT had a higher increase in the post-challenge TG-TRL levels including all TG fractions (large, medium and small).34

It is likely that reduced LPL activity contributes to postprandial increase of TG in diabetic patients.35 Regarding LPL, there is evidence that several modifiers may, through their interference, alter its activity, thus leading to TG accumulation. Specifically, ApoC-III, which is produced by the liver and intestine, is an exchangeable apolipoprotein located in the ApoA-I/C-III/A-IV gene cluster on chromosome 11q23. ApoC-III, consisting of an independent factor for CVD in humans, is found in both fasting and postprandial TG and chylomicrons.26 It has been reported that ApoC-III increases plasma TG through inhibition of LPL activity as well through enhancement of hepatic production of VLDL,26 although novel data suggest that ApoC-III may also increase plasma TG levels via an LPL-independent mechanism.36 In addition, results from experimental animal models show that ApoC-III contributes to hypertriglyceridemia mainly by inhibiting hepatic clearance of TG-rich lipoproteins via low density lipoprotein receptors (LDLRs) and LDL-related protein 1 (LRP1) which mediate the endocytotic clearance of RLPs.37 In addition, its impact on CVD prevalence is also due to stimulation of inflammatory processes in vessels and the pancreas.26 Glycosylphosphatidylinositol-anchored high density lipoprotein 1 (GPIHBP1) is expressed in capillary endothelial cells and is hypothesized to be a binding site for LPL in the capillary lumen, thereby facilitating LPL activity and TG hydrolysis along the luminan surface of capillaries.27 Moreover, it has been shown from both animal models38 and in humans with various GPIHBP1 mutations that GPIHBP1 deficiency or dysfunction seems to be associated with elevated TG levels.27 Finally, ANGPTL 3 and ANGPTL 4 are secreted proteins expressed mainly in the liver and adipose tissue, respectively, which are structurally similar to angiopoietins and their expression appears to be upregulated in insulin resistance states.39 Animal experiments have indicated that they may interfere in TG metabolism by inhibiting LPL, thus exacerbating hypertriglyceridemia.39

Another factor contributing to postprandial hypertriglyceridemia is lack of hepatic receptors (HSPG, LDLR, LRP1), which interfere with the clearance of chylomicrons and VLDL from the circulation.40 Of note, some of the hepatic lipoprotein remnant clearance receptors may interact with insulin. Specifically, it has been shown that insulin may stimulate the translocation of LRP1 to the plasma membrane, thus contributing to RLPs clearance.41 On the other hand, it has been found that inactivation of LRP1 could be associated with reduced expression of surface insulin receptors and suppressed GLUT2 translocation to plasma membrane. This will account for the fact that in experimental animals with inactivated LRP1 receptors, consumption of a high-fat diet results in insulin resistance and metabolic syndrome.42

Given that most people consume fat-containing meals frequently during the day, the usual metabolic state of lipids is postprandial, since after a typical fatty meal, consumption serum triglycerides rise within an hour and remain elevated for 5-8 hours. This contrasts with glucose metabolism which displays transient elevations after a meal.43


Complications of postprandial hyperglycemia

Postprandial hyperglycemia seems to contribute significantly to the development of cardiovascular complications, since it has been shown to enhance injury in both the macro- and microvascular systems, thus resulting in increased morbidity and mortality (Tables 1-3). Indeed, several reports strongly indicate that severe postprandial hyperglycemia is correlated with increased incidence of cardiovascular events and mortality.44-49

Data analyzed from the prospective cohort Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study, which included 3,092 adults 30-74 years old who underwent an oral glucose tolerance test, suggest that post-challenge hyperglycemia is associated with increased risk of all-cause and CVD mortality independently of other CVD risk factors.44 Similarly, pooled data from three population-based longitudinal studies showed that individuals with isolated post-challenge hyperglycemia had an increased risk of all-cause and cardiovascular mortality compared to those without diabetes. Furthermore, men with isolated post-challenge hyperglycemia had a high risk of cancer death.45 In addition, recent data have shown that the average challenge in 2-hour blood glucose level after meals was associated with the greatest difference in event-free survival probability for a composite endpoint which included CV death, nonfatal MI, nonfatal stroke, hospitalization for acute coronary syndromes or coronary revascularization.46 On the other hand, another study compared newly diagnosed diabetes patients who exhibited isolated post-challenge hyperglycemia (fasting plasma glucose <126 mg/dL and 2-h post-challenge plasma glucose ≥200 mg/dL) with patients without diabetes. During an 8-year observation period, the HR, adjusted for potential confounders for incident cardiovascular disease, was not significant [1.32 (95% CI: 0.88-1.99; p = 0.2)] in the newly diagnosed diabetic patients with isolated post-challenge hyperglycemia (fasting plasma glucose <126 mg/dL and 2-h postprandial glucose ≥200 mg/dL) compared to those without diabetes.47

Regarding the contribution of fasting versus postprandial hyperglycemia to cardiovascular events, there are reports indicating that postprandial hyperglycemia comprises a better predictor of deaths from all causes and cardiovascular disease as well as an independent factor for cardiovascular events than fasting blood glucose.48,49 Specifically, in adults of advanced age (mean age 78), postprandial glucose was associated with atherosclerotic cardiovascular disease and mortality independently of fasting glucose.50

Pulse wave velocity (PWV) is the simplest non-invasive robust assay for evaluation of arterial stiffness and, specifically, carotid-femoral PWV has been used in epidemiological studies demonstrating the predictive value of aortic stiffness for CV events.51 There are studies in subjects with post-challenge hyperglycemia detected by an OGTT or by measuring glucose levels after meal consumption. Results suggest that post-challenge/postprandial hyperglycemia correlates with a higher brachial or brachial-ankle pulse wave velocity, thus indicating a possible involvement of postprandial hyperglycemia in early-stage atherosclerosis.52-54 Carotid intima media thickness (IMT) may predict the occurrence of stroke and myocardial infarction.55 Several studies have evaluated the impact of postprandial hyperglycemia on IMT in diabetic or IGT patients.56-60 In non-diabetic patients who exhibit impaired glucose tolerance after an OGTT, post-challenge hyperglycemia appears to be associated with increased IMT.56-58 In one study, the 2h post-challenge plasma glucose and post-challenge glucose spikes were more strongly associated with carotid IMT than fasting plasma glucose and HbA1c.57 Another study noted that in non-diabetic IGT patients early hyperglycemia, and specifically the 60 minutes plasma glucose after an 75g OGTT, was significantly and positively correlated with IMT.58 Regarding diabetic patients, post-challenge glucose spikes have been shown to be independently associated with carotid IMT, implying that they may contribute to development of atherosclerosis.59 In a systematic review including 24,111 subjects (4,019 with diabetes and 1,110 with IGT), diabetic patients seemed to have a threefold increase in carotid IMT compared to patients with IGT. The authors attributed this difference to the advanced age (>10 years older) and the increased relative risks of myocardial infarction and stroke (>40%) of the diabetic participants.60 In addition, data from an experimental animal study revealed that intermittent glucose administration in female mice leads to an approximately fourfold greater atherosclerotic lesion size in their aortic sinus, thereby indicating that repetitive glucose spikes may accelerate atherosclerotic lesions formation.61 Concerning coronary atherosclerosis, Saely et al. evaluated the impact of postprandial hyperglycemia on coronary vessels in individuals with conventional diabetes (diabetes diagnosed on the basis of fasting glucose), isolated post-challenge diabetes (blood glucose ≥200 mg/dl after a 75g OGTT), IGT and normal glucose tolerance who underwent a coronary angiography for the evaluation of coronary artery disease (CAD). The results showed that coronary atherosclerosis was more frequent in patients with IGT, isolated post-challenge diabetes or conventional diabetes, with significant coronary stenosis (≥50%) being higher in patients with isolated post-challenge diabetes or conventional diabetes.62

Apart from the fact that postprandial hyperglycemia is known to cause macrovascular complications, there is evidence that it also contributes to microvascular complications. In a cross-sectional study of 232 subjects with type 2 diabetes, multiple regression analysis showed that postprandial hyperglycemia correlated independently with the incidence of diabetic retinopathy and neuropathy and non-independently with the incidence of diabetic nephropathy.63 One study also reported that in Japanese patients with type 2 diabetes, postprandial hyperglycemia was an even stronger predictor of the progression of diabetic retinopathy than HbA1c.64 Data from another study of 68 patients with DM1 and DM2 suggest that glucose variability may constitute a risk factor for diabetic retinopathy, particularly in the context of acute fluctuations and acute hyperglycemia, regardless of HbA1c.65 As far as nephropathy is concerned, a study of 12,833 individuals without a history of renal disease or diabetes indicated that impaired glucose tolerance, but not isolated impaired fasting glucose, is associated with increased GFR and a higher risk of glomerular hyperfiltration (estimated GFR above the age- and gender-specific 95th percentile for apparently healthy subjects) (OR 1.34, 95%CI: 1.107-1.66, p=0.009).66

A cross-sectional analysis of a large epidemiological study showed that postprandial hyperglycemia may affect the metabolism of certain lipoproteins. Specifically, it was demonstrated that isolated impaired glucose tolerance is associated with increased triglycerides, large very low density lipoprotein subclass particles and structural remodeling of LDL particles, in contrast to isolated impaired fasting glucose which is associated with increased ApoB and total LDL particles.67

Studies to identify the possible complications of postprandial hyperglycemia could simultaneously evaluate its contribution to overall diurnal hyperglycemia. It seems that postprandial hyperglycemia defines the main hyperglycemic state when HbA1c is low, such as in early or well controlled diabetes. In contrast, fasting hyperglycemia is much more closely associated with higher values of HbA1c (Table 4).68-70

Complications of postprandial hyperlipidemia

Large epidemiological studies have shown that postprandial hypertriglyceridemia is an additional risk factor for the development of cardiovascular disease (Tables 5, 6). Twenty-four thousand fine hundred and thirty-five (24,535) Norwegian women aged 35-49 years old were followed up for a mean of 14.6 years. Results showed that mortality from coronary heart disease, cardiovascular disease and all-cause mortality steadily increased with increasing non-fasting triglyceride concentrations.71 In addition, data from a prospective study with 26,509 initially healthy US women who underwent a follow-up for a median of 11.4 years indicated that both fasting and non-fasting triglycerides levels were predictors of such cardiovascular events as nonfatal myocardial infarction, nonfatal ischemic stroke, coronary revascularization or cardiovascular death. Furthermore, non-fasting triglyceride levels maintained a strong independent relationship with cardiovascular events in contrast to fasting levels, which demonstrated a weaker association with cardiovascular events when adjusted for total and high density lipoprotein cholesterol and measures of insulin resistance.72

As in the female population, cardiovascular risk increases in men with elevated postprandial triglycerides. A prospective cohort study including 14,916 men aged 40 to 84 years old determined that the occurrence of myocardial infarction was the main outcome during a 7-year follow-up. Triglyceride levels (85% of blood samples collected at baseline were non-fasting) exhibited a linear association with the risk for myocardial infarction, with men in the highest quintile having an approximately 2.5 greater risk than those in the lowest quintile.73 Another prospective cohort study of 7,587 women and 6,394 men aged 20-39 years from Copenhagen pointed to an association of elevated non-fasting triglycerides with myocardial infarction, ischemic heart disease and death during a mean follow-up of 26 years. Hazard ratios were higher as triglycerides levels increased.74 Additionally, it has been reported that elevated postprandial TG is linked to an increased risk of myocardial infarction, ischemic stroke and early death in women and men in the general population.75

The role of postprandial hypertriglyceridemia in the development of atherosclerosis seems to be important. There are several studies evaluating the impact of postprandial hypertriglyceridemia on carotid intima thickness in type 2 diabetic patients of various origins.76-79 The studies concluded that increased postprandial triglycerides are associated with higher IMT. Additionally, in 45 patients who underwent a standardized fatty meal test and whose triglycerides levels were subsequently measured after 2, 4, 6 and 8 hours, it was shown that high post-challenge triglycerides correlated positively with an increase in aortic pulse wave velocity (aPWV) 6 hours after the fatty meal consumption and, specifically, a 0.88 m/s rise of aPWVA was found for a 100mg/dl increase in triglycerides.80

Waist circumference, which is an index of central obesity, constitutes a well-recognized cardiovascular risk factor in hypertensive patients55 and has also been reported to be associated with such conditions as, inter alia, idiopathic portal vein thrombosis,81 asthma in children and adolescents and uncontrolled asthma in women,82,83 non-alcoholic liver disease84 and dementia.85 Oka et al conducted a study including 1,505 men and 798 women who were not taking medications for diabetes or dyslipidemia. Both fasting and 2-hours postprandial TG levels were measured and a possible association with waist circumference was tested. The results showed that waist circumference had a stronger association with postprandial TG than fasting TG.86 This finding may suggest that postprandial hypertriglyceridemia plays a role in many pathologic conditions related to central obesity.


The main pathophysiologic mechanisms participating in development of cardiovascular damage are endothelial dysfunction and oxidative stress, activation of inflammation and coagulation, and penetration of lipoprotein particles in the arterial wall (Figure 3).

Figure 3. Mechanisms involved in cardiovascular damage caused by postprandial dysmetabolism

Endothelial dysfunction is an early process in the development of cardiovascular disease and is defined as a reduced response to vasodilatory stimuli.87 It has been shown that postprandial hyperglycemia and hyperlipidemia is associated with increased production of reactive oxygen species (ROS) leading to increased oxidative stress, which subsequently mediates the development of endothelial dysfunction.87-89 It has been proposed that excess of post-meal nutrients overburden the electron transport chain in mitochondria, exceeding their metabolic ability in muscle and adipose tissue mitochondria and thus resulting in increased ROS production.1,87 Specifically regarding postprandial hypertriglyceridemia, it seems that endothelial function is mainly impaired after a high saturated fatty acid intake, while the effects of high-monounsaturated or polyunsaturated are more controversial.87

Inflammation and the pro-inflammatory state have been shown to be another significant contributor to the pathogenesis of atherosclerosis. There is evidence that postprandial hyperglycemia is associated with increased circulating cytokines levels such as IL-6 and TNFa in subjects with IGT90 and in type 2 diabetic patients.91 Concerning non-diabetic individuals, intake of a high fat meal, which leads to postprandial triglycerides increase, results in elevated cytokines.91 Ιt has been proposed that upregulation of endothelial cells adhesion molecules plays an important role in the pathogenesis of atherosclerosis through enhanced adhesion of circulating leukocytes in the endothelium.92 Circulating adhesion molecules such as the intracellular adhesion molecule (ICAM)-1 and vascular cellular adhesion molecule (VCAM)-1 have been proposed as markers of atherosclerosis and future cardiovascular events.93-95 There are data that postprandial dysmetabolism is associated with elevated circulating adhesion molecules,91,92 suggesting that postprandial dysmetabolism-induced pro-inflammatory response is a significant pathophysiologic mechanism for the development of atherosclerosis. In addition, experiments in rat models have shown that postprandial hypertriglyceridemia is associated with overexpression of ICAM-1 and increased monocyte adhesion in the aortic arterial wall.96 Recent data also demonstrate that postprandial hyperglycemia is involved in increased leucocyte activation in patients with type 2 diabetes and familial combined hyperlipidemia.97

Concerning the coagulation system, there are data demonstrating that postprandial hyperglycemia constitutes a significant predictor of platelet activation, as this was shown by measurement of urinary 11-dehydro-thromboxane (TX)B(2), a marker of in vivo platelet activation, in subjects with type 2 early diabetes.98 It has also been found that induction of acute short-term hyperglycemia in type 2 diabetic patients results in increased platelet activation markers, such as shear-induced platelet activation, P-selectin and LIMP expression on platelets, urinary 11-dehydro-TxB2 excretion and plasma vWF.99 Similarly, postprandial lipemia after the intake of fatty diets results in increased plasminogen activator inhibitor (PAI)100 and activated factor VII, with saturated fats causing a lesser increase in FVIIa than unsaturated.101

Additionally, postprandial lipids appear to have a direct impact on vessels structure and establishment of atherosclerosis, since RLPs infiltrate the subendothelial space of the arterial wall, are subsequently enriched in cholesterol and ApoE and are then phagocytized by arterial wall macrophages.23


It is noteworthy that postprandial dysmetabolism, apart from being a risk factor for cardiovascular disease, also seems to be involved in other conditions like polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD). A recent study in 163 adolescents fulfilling diagnostic criteria for PCOS showed that 17.2% of PCOS patients exhibited abnormal glucose metabolism after an OGTT (16% had IGT and 1.2% had diabetes), while only two patients were detected with hyperglycemia based on fasting glucose values. In addition, all patients with abnormal glucose metabolism were overweight or obese.102 Kyaw Tun et al. compared glucose, insulin and lipids responses after a mixed meal in 26 obese PCOS women and 26 obese controls: the results revealed that AUC-TG, AUC-glucose and AUC-insulin were higher, while AUC-HDL was lower in PCOS women after the meal, with AUC-insulin and iAUC-insulin remaining higher after adjustment for BMI and HOMA-IR.103 Another study compared post-challenge glucose and lipids responses after an OGTT and an oral fat tolerance test (OFTT) between 20 lean (BMI 23.5±2.6 Kg/m2) PCOS women and 20 BMI-matched controls (BMI: 23.1±3.1 kg/m2): it was found that HOMA-IR, AUC-glucose, AUC-TG, AUC-VLDL and AUC-total cholesterol were higher in PCOS women.104 All the aforementioned findings indicate that postprandial dysmetabolism is involved in PCOS syndrome, with obesity and insulin resistance playing an important role in its occurrence in these patients. In fact, the actual pathogenetic mechanisms of glucose dysmetabolism in PCOS women appear to be multifactorial with impaired insulin action, beta cell dysfunction and decreased hepatic clearance of insulin being implicated. Moreover, insulin resistance and hyperinsulinemia appear to contribute to hyperandrogenemia and anovulation which characterize PCOS.105

Of note, a proportion of PCOS women also exhibit NAFLD. In a study of 83 PCOS women (without a history of alcohol intake, chronic liver disease or medication causing hepatotoxicity or elevated liver enzymes) who were compared to 64 healthy controls, it was found that overweight/obese, but not lean, PCOS subjects exhibited higher serum levels of ALT and γGT. In addition, multiple regression analysis revealed that BMI and HOMA-IR were major determinants of ALT and γGT.106

Regarding NAFLD in the non-PCOS population, there is also evidence that there is a correlation with postprandial dysmetabolism. One hundred seventy-three (173) biopsy-proven NAFLD patients without prior known type 2 diabetes underwent a 75g OGTT. Impaired glucose tolerance, including diabetes, was detected in 60% of the NAFLD patients. In addition, post-challenge hyperinsulinemia at 120 min after the test was associated with advanced fibrosis (P = 0.0001, OR: 3.56; 95% CI, 1.61-7.86).107 Similarly, another study with 111 NAFLD patients showed that when an OGTT was performed in patients with non-established type 2 diabetes, 33% of them revealed abnormal glucose tolerance (IGT or diabetes). In addition, fasting hyperglycemia was of limited sensitivity (46%) but high specificity (89%) for identifying those patients, while all of them had post-challenge hyperinsulinemia.108 Concerning NAFLD and postprandial lipids, there is evidence that non-obese non-diabetic normolipidemic patients with non-alcoholic steatohepatitis (NASH) manifest postprandially pronounced intestinal and hepatic VLDL1 accumulation and LDL lipid peroxidation and, moreover, that steatosis is independently associated with postprandial intestinal VLDL1.109 It has also been shown in healthy subjects who underwent an oral fat load that those with increased liver fat (>5% as determined by magnetic resonance spectroscopy) exhibit increased post-challenge AUC-plasma TG, AUC-chylomocron TG, AUC-VLDL2TG and AUC-chylomicron ApoB100 compared to those with normal liver fat.110


a) Detecting postprandial hyperglycemia

The conventional methods for the detection of postprandial hyperglycemia are the 75g OGTT and self-monitoring of blood glucose (SMBG). IGT is defined as plasma glucose levels 140-199mg/dl after a 75g OGTT, while levels ≥200mg/dl are a criterion for the diagnosis of diabetes.111

Guidelines for management of post-meal glucose in diabetes currently recommend SMBG as being the optimal method for assessing plasma glucose levels in insulin and non-insulin treated type 2 diabetic patients and propose that the timing and frequency of SMBG be individualized to each person’s treatment regimen and level of glycemic control.112

Emerging technologies for the evaluation of postprandial glucose levels include continuous glucose monitoring (CGM) and plasma 1,5-anhydroglucitol (1,5-AG).112 CGM employs a sensor measuring interstitial glucose every 1-10 min, which then transmits this reading to a data storage device. 1,5-AG is a natural dietary polyol and has been proposed as a marker for post-meal hyperglycemia. Stettler et al. performed a prospective study at three large Swiss hospitals and found that 1,5-AG best reflected the 2-hour postprandial glucose values of the two previous weeks.113 These findings are consistent with recent data from type 1 diabetic patients monitored with CGM in whom the change in 1,5-AG level was significantly correlated with changes in glycemic control, mean post-meal maximum glucose and area under the curve for glucose above 180mg/dL.114

b) Detecting postprandial hypertriglyceridemia

In contrast to postprandial hyperglycemia, there are currently no available standardized or validated protocols and cut-off points for the assessment of postprandial hypertriglyceridemia.1 The Endocrine Society Clinical Practice Guidelines for the evaluation and treatment of hypertriglyceridemia indicate that although postprandial lipid levels may be a more potent predictor of cardiovascular disease risk than fasting triglycerides, it is recommended that the diagnosis of hypertriglyceridemia at present be based on fasting TG levels due to lack of standardization and reference levels of non-fasting TG or RLPs.115 Similarly, the American Association of Clinical Endocrinologists Guidelines for management of dyslipidemia and prevention of atherosclerosis point out the lack of an assessment and of a standardized reference range for non-fasting TG. They however emphasize that elevated postprandial TG can no longer be ignored as indicative of no increased CHD risk and also refer to several studies which suggest that non-fasting TG exceeding the usual fasting cut-off points (≥150mg/dl) are independently associated with increased CAD risk.116 The 2011 European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Guidelines for the management of dyslipidemias state that the use of non-fasting TG is still debated.154 Also mentioned is the fact that non-HDL-C has proved to be a good surrogate marker of TG and remnants.154 Several biochemical procedures have been used for the evaluation of postprandial plasma chylomicrons and their remnants (triglyceride-rich lipoprotein fractions, remnant-lipoprotein cholesterol, retinylesters, chylomicron-like emulsion, sodium dodecyl sulphate-polyacrylamide gel electrophoresis, immunoblotting, enzyme-linked immunoabsorbent assays, C13 breath test capillary finger prick), which nevertheless are not equivalent in specificity, cost and applicability.117 Su et al propose identification of ApoB48 with ELISA, along with capillary triglyceride measurements, as the most clinically potent methods for the determination of postprandial lipid metabolism.117 There are also data indicating that in young healthy subjects, fasting triglyceride-rich lipoproteins are useful predictors of postprandial hyperlipidemia, thereby pointing to a potential effective method that avoids the use of inconvenient meal loading tests.118 It would be interesting to evaluate the utility of this assay in other population groups, such as in older, obese or diabetic individuals. Regarding the determination of optimal cut-off points for the detection of postprandial hyperlipidemia, White et al. suggest an optimal non-fasting triglyceride threshold of 175mg/dl, which corresponds to a HR for cardiovascular events of 1.88 (95% CI 1.52-2.33, P <0.001).119


Major curative interventions aiming at postprandial dysmetabolism treatment are dietary modification, exercise, weight loss and medication aiming at amelioration of postprandial glucose and triglycerides values. The American Diabetes Association Guidelines recommend a target of peak postprandial capillary plasma glucose (measurements should be made 1-2 hours after the beginning of the meal) <180mg/dl (10mmol/l) for non-pregnant adults with diabetes.111 Given the fact that postprandial glucose values >7.8mmol/l are associated with an increase in all-cause mortality and values, while >10mmol/l is associated with both microvascular complications and higher risk for MI, the Canadian Diabetes Association Guidelines recommend a 2-hour postprandial glucose target of 5-10mmol/l in diabetic patients in order to achieve an A1c ≤7%. Ιf, however, the A1c target of ≤7% cannot be achieved, they recommend a further lowering of the postprandial glucose target to 5-8 mmol/l.120

Dietary modification and exercise

The international guidelines recommend lifestyle modification in individuals with IGT in order to delay conversion to type 2 diabetes. Weight loss, increased physical activity and an appropriate intake of total energy with a diet in which fiber and low fat protein sources predominate have been seen to be effective.111,120,121

The contribution of a well-designed and balanced diet is important for postprandial dysmetabolism treatment. Modern diets have been shown to be involved in meal-induced inflammation and postprandial oxidative stress.122 In addition, recent data indicate that fast food consumption induces greater and sustained overall cardiac workload (prolonged elevations in resting heart rate and prolonged elevations in diastolic workload) in patients with type 2 diabetes.123 In contrast, the Mediterranean diet which is low in caloric density but rich in nutrient density has been associated with better cardiovascular health.1

Consumption of fiber is beneficial for postprandial dysmetabolism amelioration. Specifically, it has been shown that a diet rich in vegetables, fruits and whole cereals decreases both postprandial glucose and triglyceride-rich lipoproteins.124,125 In addition, a meal high in fruit and fiber is associated with alterations in several factors which may result in improved postprandial glucose and lipid values and in restriction of inflammatory response. These alterations include higher proinsulin, insulin, C-peptide, GIP and peak GLP-1 secretion and lower plasma glucagon, dipeptidyl peptidase-IV (DPP-IV) and CD26 expression in mononuclear cells (MNC) compared to a high fat and carbohydrate meal.126

Regarding carbohydrates, both the type and amount of carbohydrates consumed are crucial for the increase of postprandial glucose. A low glycemic index diet appears to result in lower postprandial glucose levels as well as in lower fasting apolipoprotein B concentration.127 The glycemic index measures the glycemic effect of meal carbohydrate compared to the effect of an equal amount of glucose and is estimated as a percentage of the blood glucose area under the curve 2 hours after food consumption compared to the same area under the curve after the same amount of carbohydrate was taken as glucose.128,129 In addition, it seems that consumption of meals containing high amounts of carbohydrates contributes to post-meal glucose excursions in individuals both with impaired glucose regulation and with normal glucose tolerance, with postprandial glucose fluctuations increasing gradually with increased proportions of consumed carbohydrates.130

The ESC and the EAS Guidelines for the management of dyslipidemias state that a high monounsaturated fat diet significantly improves insulin sensitivity and reduces postprandial TG levels compared to a high saturated fat diet.154 There is evidence that consumption of omega-3 fatty acids may improve postprandial lipid metabolism, curbing elevations of triglycerides, ApoB48, remnant lipoprotein-cholesterol levels in healthy subjects, decreasing postprandial triglyceride and ApoB48 in obese individuals combined with an hypocaloric diet and reducing postprandial triacylglycerol levels in hypertriglyceridemic patients.131-133

It is noteworthy that type 2 diabetic patients seem to exhibit reduced post-breakfast glucose excursion when consuming a high protein breakfast compared to a high carbohydrate breakfast meal.134 Similarly, hypertriglyceridemic individuals who consume a low protein diet appear to develop an exaggerated postprandial chylomicron response, as indicated by increased postprandial ApoB48.135

Exercise and concomitant weight loss also have an important role in the management of postprandial dysmetabolism. The American Diabetes Association Guidelines recommend a target of 7% weight loss and increase of their moderate-intensity physical activity to at least 150 min/week.111 A meta-analysis of 11 studies, including aerobic exercise, resistance exercise or a combination of these, concluded that exercise decreased significantly average glucose concentrations (-0.8 mmol/L, p <0.01) and daily time spent in hyperglycemia (-129 minutes, p <0.01) but did not have an impact on fasting glucose in patients with type 2 diabetes.136 This finding strengthens the beneficial impact of exercise on postprandial glucose metabolism. As far as postprandial lipid metabolism is concerned, it seems that exercise improves postprandial triglyceride levels in overweight young women and men with metabolic syndrome and in type 2 diabetic patients.137-139 Moreover, there are data indicating that weight loss after bariatric surgery may result in lower postprandial plasma glucose values in both obese and non-obese type 2 diabetic patients.140,141

Pharmacological treatment targeting postprandial hyperglycemia

Concerning IGT, the Canadian Diabetes Association recommends pharmacological therapy with metformin or acarbose for individuals with IGT in order to reduce the risk of type 2 diabetes (Grade A, Level 1A).120 The American Diabetes Association Guidelines, on the other hand, do not distinguish between individuals with IGT and those with IFG and recommends consideration of metformin therapy in individuals with prediabetes and BMI >35, in those aged <60 years, in women with prior gestational diabetes mellitus and in those with rising A1C despite lifestyle intervention.111

The International Diabetes Federation Guideline Development Group states that the pharmacologic agents that mainly affect postprandial glucose values in diabetic patients are: α-glucosidase inhibitors (AGIs), meglitinides, short-acting sulfonylureas, short-acting insulin, GLP1 analogs, DDP4 inhibitors and pramlitidine.112

AGIs act in the intestine through inhibition of α-glycosidases which are located in the gut epithelium and convert oligosaccharides and polysaccharides to easily absorbed monosaccharides. AGIs thus reduce carbohydrates absorption. They are effective in lowering postprandial glucose levels and, of note, they also blunt postprandial lipids spikes. Moreover, they possess additional pleiotropic effects, such as increase of GLP-1 postprandial circulating levels, oxidative stress reduction, prevention of endothelial dysfunction and promotion of weight loss. Their main adverse effect is flatulence and other gastrointestinal symptoms.142,143

Meglitinides (repaglinide and nateglinide) are short-acting insulin secretagogues which act to restore the disrupted early-phase secretion of postprandial insulin. They are administered 15 minutes before a meal and their action begins within 30 minutes of meal inception. Their main adverse effect is hypoglycemia.144 A randomized multicenter clinical trial in type 2 diabetic patients showed that after a 16-week therapy, both repaglinide and nateglinide seemed to have a similar postprandial glycemic effect, although repaglinide was more effective in reducing HbA1c and fasting plasma glucose.145 Concerning the effectiveness of meglitinides in reducing postprandial hyperglycemia complications compared to other insulin secretagogues, a randomized single-blind trial on 175 drug-naïve type 2 diabetic patients showed that repaglinide for 12 months resulted in regression of carotid intima-media thickness in a greater proportion of diabetics compared to glyburide (52% vs 18%, p<0.01). In addition, inflammation markers, such as CRP and IL-6, decreased more in the repaglinide vs the glyburide group. These observations were accompanied by statistically significant changes in postprandial but not fasting hyperglycemia.146

GLP1 receptor agonists (exenatide, exenatide LAR, liraglutide, lixisenatide) are synthetic GLP1 analogs resistant to DDP4 disruption which demonstrate the same actions as endogenous GLP1.14 The GLP1 analogs that primarily aim at lowering postprandial glucose are exenatide and lisixenatide, while exenatide LAR and liraglutide mainly affect fasting plasma glucose.14 The main reason that short-acting GLP1 receptor agonists (exenatide, lisixenatide) seem to be more effective in reducing postprandial glucose levels appears to be related to the rate of gastric emptying rather than their effect on insulin release.147 It seems that short-acting GLP1 receptor agonists cause a more sustained delay in gastric emptying than the longer-acting ones.147 There is clinical evidence that exenatide improves postprandial hyperglycemia through deceleration of gastric emptying, enhancement of visceral glucose uptake, inhibition of glucagon secretion and stimulation of insulin secretion. These mechanisms contribute to an improvement of prandial glycemia and a reduction of body weight.148 The American Diabetes Association Guidelines propose adding a GLP-1 receptor agonist in order to cover postprandial glucose excursions in diabetic patients treated with basal insulin when A1C remains above target despite achievement of an acceptable fasting glucose level.111 Moreover, recent large double-blind trials have evaluated the impact of GLP1 receptors agonists on cardiovascular morbidity and mortality in patients with type 2 diabetes.149,150 The ELIXA trial is a multicenter, randomized, double-blind, placebo-controlled trial which enrolled 6,068 type 2 diabetic patients with a recent acute coronary heart syndrome who were randomized to receive lixisenatide or placebo in addition to concomitant glucose-lowering agents in accordance with the local clinical guidelines. After a median of 25 months of follow-up, results showed non-inferiority of lixisenatide to placebo (p<0.001) with respect to a primary composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for unstable angina.149 The LEADER trial is a multicenter, double-blind, placebo-controlled trial which included 9,340 patients with type 2 diabetes and high cardiovascular risk who were randomized to receive liraglutide or placebo in addition to standard care. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke. After a 3.8-year median follow-up, it was shown that the primary outcome was achieved in fewer patients in the liraglutide group (608 of 4,668 patients [13.0%]) than in the placebo group [694 of 4,672 (14.9%)] [hazard ratio, 0.87; 95% confidence interval (CI), 0.78 to 0.97; P<0.001 for non-inferiority; P=0.01 for superiority].150

DPP4 inhibitors (sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin) inhibit the DPP4 enzyme which physiologically inactive GLP1 and GIP through disintegration. They are effective in reducing plasma glucose levels in the postprandial and the fasting state. They have no effect on body weight and they are safe with respect to causing hypoglycemia.151 The various DPP4 inhibitors are similar concerning their antihyperglycemic properties.151 Regarding the effectiveness of DPP4 in reducing postprandial hyperglycemia compared to other hypoglycemic agents targeting postprandial glucose, a recent study in 19 type 2 diabetics inadequately controlled by diet and exercise indicated that the effects of sitagliptin on postprandial glucose levels were similar to those of nateglinide.152

Pramlitidine is a synthetic analog of amylin which may be used with mealtime insulin in type 1 and type 2 diabetic patients.153 Moreover, it may be used in type 2 diabetics in addition to monotherapy with metformin or sulfonylurea or to combined therapy with metformin and sulfonylurea, with or without insulin therapy. It is effective in reducing postprandial glucose by 4-6 mmol/l and may be useful in reducing the dose of administered insulin.153 In addition, it may contribute to weight reduction, which however seems to be transient. The most common adverse effect is transient nausea.153

Pharmacological treatment targeting postprandial hypertriglyceridemia

So far, the guidelines do not recommend pharmacological treatment aiming to ameliorate postprandial hypertriglyceridemia, nor do they delineate specific targets.115,116,154 Αntilipidemic agents are typically used for treatment of fasting hyperlipidemia. Nevertheless, there are data suggesting that they may also play an important role in the management of postprandial hyperlipidemia.


Statins reduce the synthesis of cholesterol in the liver by competitively inhibiting HMG-CoA reductase activity and they are moreover considered as useful pharmacologic therapy for the treatment of fasting hypertriglyceridemia.154 There is evidence that they may also improve postprandial lipoprotein metabolism.155 There are data indicating that 4 weeks therapy of atorvastatin 10mg daily may decrease postprandial large triglyceride-rich lipoproteins (containing chylomicrons) in hypertriglyceridemic patients.156 In addition, it has been shown that pitavastatin 2mg/day may result in reduction of both postprandial hypertriglyceridemia and endothelial dysfunction in obese subjects and in patients with stable coronary artery heart disease.157,158 Simvastatin 80mg has also been seen to be effective in reducing postprandial plasma triglyceride levels and triglyceride-content in lipoprotein fractions in male obese patients with metabolic syndrome.159


Ezetimibe inhibits the intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients, thus resulting in upregulation of hepatic LDL receptor and subsequently in increased LDL-cholesterol clearance from the circulation.154 Trials in overweight/obese men with hypertriglyceridemia report that the administration of ezetimibe at a dose of 10mg/day resulted in reduction in postprandial serum triglyceride excursion as well as in fasting and postprandial ApoB48 levels.160,161 Similar results have been noted in type 2 diabetic subjects when the same dose of ezetimibe (10mg/day) was added to a lipid lower treatment with simvastatin 20mg.162 In addition, it seems that this medication may suppress postprandial endothelial dysfunction, as this has been assessed by brachial artery flow-mediated dilation.163 In respect to ezetimibe efficacy in ameliorating postprandial hyperlipidemia compared to statin therapy, a multicenter, double-blind, crossover trial in 100 abdominally obese patients with metabolic syndrome showed that adding 10mg ezetimibe to a low dose statin treatment (10mg simvastatin) has an equal effect compared to a high dose statin treatment (simvastatin 80mg) in postprandial plasma lipids as well as in fasting and postprandial change of endothelial function.164


Fibrates interfere with lipoprotein metabolism, decreasing the production and increasing the catabolism of triglyceride-rich lipoproteins through the activation of peroxisome proliferator-activated receptor-alpha (PPAR-α). They are effective in lowering both fasting and postprandial triglycerides and triglyceride-rich lipoprotein (TRL) remnant particles.154,165 It has also been suggested that fenofibrate may reduce fasting and postprandial inflammatory response and oxidative stress as it has been shown to reduce inflammation markers such as soluble vascular cell adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) as well as oxidized fatty acids.166 Concerning the comparison of fibrates efficacy with other lipid lowering agents or their potential synergistic effect, a randomized controlled clinical trial with 47 type 2 diabetics with hypertriglyceridemia showed that gemfrozile 1200mg/d alone did not differ in decreasing postprandial serum triglyceride compared to gemfrozile 1200mg/d plus ezetimibe 10mg/d or atorvastatin 10mg/d plus ezetimibe 10mg/d, and that fasting serum ApoB was reduced only in subjects receiving a regimen containing ezetimibe.167

The ACCORD lipid trial evaluated the effect of intensive lipid plasma treatment on cardiovascular outcomes in type 2 diabetic patients. Five thousand five hundred eighteen (5,518) type 2 diabetics who were treated with simvastatin were randomly assigned to receive fenofibrate or placebo and the primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke or death from cardiovascular causes after a 4.7-year mean follow-up.168 No significant difference was found between the fenofibrate group and the placebo group with respect to the primary outcome. However, there was a subgroup of patients with both a baseline TG level in the highest third (mean 284mg/dl) and an HDL level in the lowest third (mean 29.5 mg/dl) who seemed to benefit from treatment with fenofibrate.168 High fasting TG and low fasting HDL forms a well-recognized component of the metabolic syndrome which is also characterized by several other lipid and lipoprotein abnormalities, such as elevated postprandial TG, small dense LDL and ApoB containing particles including chylomicrons and VLDL.154 Moreover, an ancillary study in a subset of subjects of the ACCORD lipid trial showed that administering fenofibrate 145mg/dl to type 2 diabetics receiving simvastatin resulted in reduction of both postprandial triglycerides and postprandial ApoB levels.169 However, it seems that the overall baseline TG levels in these subjects were lower (median=99) and the HDL levels were higher (mean=38.9±10mg/dl) than in the subgroup, who appeared to have benefited from fenofibrate therapy in the original ACCORD lipid trial.168,169 These data may indicate that fenofibrate therapy may ameliorate postprandial dyslipidemia in subjects with low HDL and high fasting TG, such as type 2 diabetics and individuals with metabolic syndrome, but further studies need to be conducted.

Apart from the well-established hypolipidemic agents, it seems that orlistat, a drug which promotes weight loss by inhibiting intestinal lipase, may lower postprandial TG levels as stated by the Endocrine Society Clinical Practice Guidelines for evaluation and treatment of hypertriglyceridemia.115 It is also interesting that pharmacological agents targeted at postprandial hyperglycemia could also play a role in amelioration of postprandial hypertriglyceridemia. Specifically, there is clinical evidence that incretin-based therapies like exenatide and DPP4 inhibitors may play an important role in lowering postprandial lipids and lipoproteins concentrations and postprandial lipids spikes.25 It has been also shown that acarbose might reduce postprandial triglycerides, serum-remnant like particle (RLP) cholesterol, chylomicrons and free fatty acids.142


Postprandial dysmetabolism is a non-fasting state characterized by elevated levels of plasma glucose and triglyceride containing lipoproteins (chylomicrons, VLDL, RLPs). Accumulating data indicate that postprandial dysmetabolism contributes to the development of atherosclerosis, while it has also been demonstrated that it comprises a risk factor for increased cardiovascular morbidity and mortality. Clearly, postprandial hyperglycemia contributes to microvascular complications such as nephropathy and retinopathy. The main pathophysiologic mechanisms participating in development of cardiovascular damage are endothelial dysfunction and oxidative stress, activation of inflammation and coagulation mechanisms and facilitating the penetration of lipoprotein particles into the arterial wall.

The conventional methods for the detection of postprandial hyperglycemia are the 75g OGTT and SMBG, while emerging technologies for the evaluation of postprandial glucose levels include CGM and plasma 1,5-anhydroglucitol (1,5-AG). In contrast to postprandial hyperglycemia detection and screening, there are no currently available standardized or validated protocols and cut-off points for the assessment of postprandial hypertriglyceridemia.

The management of postprandial dysmetabolism includes firstly lifestyle modification strategies with diet, exercise, weight loss and, if deemed necessary, the administration of a variety of pharmaceutical agents. Regarding medical treatment, acarbose, meglitinide analogs, short-acting insulin and the novel GLP-1 receptor agonists, DDP-4 inhibitors and pramlitidine are effective in ameliorating postprandial hyperglycemia, while some of these hypoglycemic agents such as acarbose, exenatide and DPP-4 receptor agonists seem also to be effective in postprandial hyperlipidemia treatment. Drugs which are conventionally used for the treatment of fasting dyslipidemias, such as statins, ezetimibe and fibrates, also appear to play an important role in managing postprandial dyslipidemia. However, future trials are required exploring not just isolated blood measurements, but mainly the actual tissue damage and the reversibility of postprandial dysmetabolism long-term complications.


1. O’Keefe JH, Bell DS, 2007 Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 100: 899-904.
2. Aron off SL, Berkowitz K, Shreiner B, Want L, 2004 Glucose Metabolism and Regulation: Beyond Insulin and Glucagon. Diabetes spectrum 17: 183-190.
3. Grodsky GM, 1972 A threshold distribution hypothesis for packet storage of insulin and its mathematical modeling. J Clin Invest 51: 2047-2059.
4. Kahn SE, 2000 The importance of the beta cell in the pathogenesis of type 2 diabetes mellitus. Am J Med 108: Suppl 6a: 2-8.
5. Lin Z, Zhou J, Li X, et al, 2015 High-normal 2h glucose is associated with defects of insulin secretion and predispose to diabetes in Chinese adults. Endocrine 48: 179-186.
6. Guillausseau PJ, Meas T, Virally M, Laloi-Michelin M, Médeau V, Kevorkian JP, 2008 Abnormalities in insulin secretion in type 2 diabetes mellitus. Diabetes Metab 34:Suppl 2: 43-48.
7. Huang S, Czech MP, 2007 The GLUT4 glucose transporter. Cell Metab: 237-252.
8. Taborsky GJ Jr, 2010 The physiology of glucagon. J Diabetes Sci Technol 4: 1338-1344.
9. Lund A, Bagger JI, Christensen M, Knop FK, Vilsboll T, 2014 Glucagon and type 2 diabetes: the return of the alpha cell. Curr Diab Rep 14: 555.
10. Akter R, Cao P, Noor H, et al, 2016 Islet amyloid polypeptide: structure, function, and pathophysiology. J Diabetes Res 2016: 2798269.
11. Roth JD1, Hughes H, Kendall E, Baron AD, Anderson CM, 2006 Antiobesity effects of the beta-cell hormone amylin in diet-induced obese rats: effects on food intake, body weight, composition, energy expenditure, and gene expression. Endocrinology 147: 5855-5864.
12. Deacon CF, Ahren B, 2011 Physiology of incretins in health and disease. Rev Diabet Stud 8: 293-306.
13. Holst JJ, Knop FK, Vilsbøll T, Krarup T, Madsbad S, 2012 Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. Diabetes Care 34:Suppl 2: 251-257.
14. Gerich J, 2013 Pathogenesis and management of postprandial hyperglycemia: role of incretin-based therapies. Int J Gen Med 6: 877-895.
15. Drucker DJ, 2006 The biology of incretin hormones. Cell Metab 3: 153-165.
16. Calanna S, Christensen M, Holst JJ, et al, 2013 Secretion of glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Systematic review and meta-analysis of clinical studies. Diabetes Care 36: 3346-3352.
17. Calanna S, Christensen M, Holst JJ, et al, 2013 Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies. Diabetologia 56: 965-972.
18. Xu G, Kaneto H, Laybutt DR, Duvivier-Kali VF, Trivedi N, Suzuma K, 2007 Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: possible contribution to impaired incretin effects in diabetes. Diabetes 56: 1551-1558.
19. Kim W, Egan JM, 2008 The role of incretins in glucose homeostasis and diabetes treatment. Pharmacol Rev 60: 470-512.
20. Amato A, Baldassano S, Mulè F, 2016 GLP2: an underestimated signal for improving glycaemic control and insulin sensitivity. J Endocrinol 229: R57-66.
21. Meier JJ, Nauck MA, Pott A, et al, 2006 Glucagon-like peptide 2 stimulates glucagon secretion, enhances lipid absorption, and inhibits gastric acid secretion in humans. Gastroenterology 130: 44-54.
22. Schmidt WE, Siegel EG, Creutzfeldt W, 1985 Glucagon-like peptide-1 but not glucagon-like peptide-2 stimulates insulin release from isolated rat pancreatic islets. Diabetologia 28: 704-707.
23. Chan DC, Pang J, Romic G, Watts GF, 2013 Postprandial hypertriglyceridemia and cardiovascular disease: current and future therapies. Curr Atheroscler Rep 15: 309.
24. Vergès B, 2015 Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia 58: 886-899.
25. Ansar S, Koska J, Reaven PD, 2011 Postprandial hyperlipidemia, endothelial dysfunction and cardiovascular risk: focus on incretins. Cardiovasc Diabetol 10: 61.
26. Kohan AB, 2016 ApoC-III: a potent modulator of hypertriglyceridemia and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes 22: 119-125.
27. Young SG, Davies BS, Voss CV, et al, 2011 GPIHBP1, an endothelial cell transporter for lipoprotein lipase. J Lipid Res 52: 1869-1884.
28. Saponaro C, Gaggini M, Carli F, Gastaldelli A, 2015 The subtle balance between lipolysis and lipogenesis: a critical point in metabolic homeostasis. Nutrients 7: 9453-9474.
29. Parlevliet ET, Wang Y, Geerling JJ, et al, 2012 GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice. PLoS One 7: e49152.
30. Hsieh J, Trajcevski KE, Farr SL, et al, 2015 Glucagon-like peptide 2 (GLP-2) stimulates postprandial chylomicron production and postabsorptive release of intestinal triglyceride storage pools via induction of nitric oxide signaling in male hamsters and mice. Endocrinology 156: 3538-3547.
31. Blackburn P, Lamarche B, Couillard C, et al, 2003 Postprandial hyperlipidemia: another correlate of the “hypertriglyceridemic waist” phenotype in men. Atherosclerosis 171: 327-336.
32. Couillard C, Bergeron N, Prud’homme D, et al, 1998 Postprandial triglyceride response in visceral obesity in men. Diabetes 47: 953-960.
33. Choi SH, Ginsberg HN, 2011 Increased very low density lipoprotein secretion, hepatic steatosis and insulin resistance. Trends Endocrinol Metab 22: 353-363.
34. Blackburn P, Lamarche B, Couillard C, Pascot A, Tremblay A, Bergeron J, 2003 Contribution of visceral adiposity to the exaggerated postprandial lipemia of men with impaired glucose tolerance. Diabetes Care 26: 3303-3309.
35. Pruneta-Deloche V, Sassolas A, Dallinga-Thie GM, Berthezène F, Ponsin G, Moulin P, 2004 Alteration in lipoprotein lipase activity bound to triglyceride-rich lipoproteins in the postprandial state in type 2 diabetes. J Lipid Res 45: 859-865.
36. Gaudet D, Brisson D, Tremblay K, et al, 2014 Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med 371: 2200-2206.
37. Gordts PL, Nock R, Son NH, et al, 2016 ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors. J Clin Invest 126: 2855-2866.
38. Beigneux AP, Davies BS, Gin P, et al, 2007 Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 plays a critical role in the lipolytic processing of chylomicrons. Cell Metab 5: 279-291.
39. Köster A, Chao YB, Mosior M, et al, 2005 Transgenic angiopoietin-like (angptl)4 overexpression and targeted disruption of angptl4 and angptl3: regulation of triglyceride metabolism. Endocrinology 146: 4943-4950.
40. Foley EM, Gordts PL, Stanford KI, Gonzales JC, Lawrence R, Stoddard N, 2013 Hepatic remnant lipoprotein clearance by heparan sulfate proteoglycans and low-density lipoprotein receptors depend on dietary conditions in mice. Arterioscler Thromb Vasc Biol 33: 2065-2074.
41. Laatsch A, Merkel M, Talmud PJ, Grewal T, Beisiegel U, Heeren J, 2009 Insulin stimulates hepatic low density lipoprotein receptor-related protein 1 (LRP1) to increase postprandial lipoprotein clearance. Atherosclerosis 204: 105-111.
42. Ding Y, Xian X, Holland WL, Tsai S, Herz J, 2016 Low-density lipoprotein receptor-related protein-1 protects against hepatic insulin resistance and hepatic steatosis. EBioMedicine 7: 135-145.
43. Lairon D, Lopez-Miranda J, Williams C, 2007 Methodology for studying postprandial lipid metabolism. Eur J Clin Nutr 61: 1145-1161.
44. Saydah SH, Miret M, Sung J, Varas C, Gause D, Brancati FL, 2001 Postchallenge hyperglycemia and mortality in a national sample of U.S. adults. Diabetes Care 24: 1397-1402.
45. Shaw JE, Hodge AM, de Courten M, Chitson P, Zimmet PZ, 1999 Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality. Diabetologia 42: 1050-1054.
46. Strojek K, Raz I, Jermendy G, et al, 2016 Factors associated with cardiovascular events in patients with type 2 diabetes and acute myocardial infarction. J Clin Endocrinol Metab 101: 243-253.
47. Barzin M, Hosseinpanah F, Malboosbaf R, Hajsheikholeslami F, Azizi F, 2013 Isolated post-challenge hyperglycaemia and risk of cardiovascular events: Tehran lipid and glucose study. Diab Vasc Dis Res 10: 324-329.
48. DECODE Study Group, the European Diabetes Epidemiology Group, 2001 Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 161: 397-405.
49. Cavalot F, Petrelli A, Traversa M, Bonomo K, Fiora E, Conti M, 2006 Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga diabetes study. J Clin Endocrinol Metab 91: 813-819.
50. Brutsaert EF, Shitole S, Biggs ML, et al, 2016 Relations of postload and fasting glucose with incident cardiovascular disease and mortality late in life: The cardiovascular health study. J Gerontol A Biol Sci Med Sci 71: 370-377.
51. Laurent S, Cockcroft J, Van Bortel L, et al, 2006 Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J 27: 2588-2605.
52. Gordin D, Saraheimo M, Tuomikangas J, et al, 2016 Influence of postprandial hyperglycemic conditions on arterial stiffness in patients with type 2 diabetes. J Clin Endocrinol Metab Jan 101: 1134-1143.
53. Ando T, Okada S, Niijima Y, et al, 2010 Impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early-stage atherosclerosis. Diabet Med 27: 1430-1435.
54. Gong W, Lu B, Yang Z, et al, 2009 Early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus and impaired glucose tolerance. Diabetes Metab 35: 458-462.
55. Mancia G, Fagard R, Narkiewicz K, et al, 2013 ESH/ESC Practice Guidelines for the Management of Arterial Hypertension. Blood Press 23: 3-16.
56. Hanefeld M, Koehler C, Schaper F, Fuecker K, Henkel E, Temelkova-Kurktschiev T, 1999 Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals. Atherosclerosis 144: 229-235.
57. Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Fuecker K, Hanefeld M, 2000 Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care 23: 1830-1834.
58. Tanaka K, Kanazawa I, Yamaguchi T, Sugimoto T, 2014 One-hour post-load hyperglycemia by 75g oral glucose tolerance test as a novel risk factor of atherosclerosis. Endocr J 61: 329-334.
59. Hu Y, Liu W, Huang R, Zhang X, 2010 Postchallenge plasma glucose excursions, carotid intima-media thickness, and risk factors for atherosclerosis in Chinese population with type 2 diabetes. Atherosclerosis 210: 302-306.
60. Brohall G, Odén A, Fagerberg B, 2006 Carotid artery intima-media thickness in patients with Type 2 diabetes mellitus and impaired glucose tolerance: a systematic review. Diabet Med 23: 609-616.
61. Shuto Y, Asai A, Nagao M, Sugihara H, Oikawa S, 2015 Repetitive glucose spikes accelerate atherosclerotic lesion formation in C57BL/6 Mice. PLoS One 10: e0136840.
62. Saely CH, Drexel H, Sourij H, Aczel S, Jahnel H, Zweiker R, 2008 Key role of postchallenge hyperglycemia for the presence and extent of coronary atherosclerosis: an angiographic study. Atherosclerosis 199: 317-322.
63. Shiraiwa T, Kaneto H, Miyatsuka T, Kato K, Yamamoto K, Kawashima A, 2005 Post-prandial hyperglycemia is an important predictor of the incidence of diabetic microangiopathy in Japanese type 2 diabetic patients. Biochem Biophys Res Commun 336: 339-345.
64. Shiraiwa T, Kaneto H, Miyatsuka T, et al, 2005 Postprandial hyperglycemia is a better predictor of the progression of diabetic retinopathy than HbA1c in Japanese type 2 diabetic patients. Diabetes Care 28: 2806-2807.
65. Sartore G, Chilelli NC, Burlina S, Lapolla A, 2013 Association between glucose variability as assessed by continuous glucose monitoring (CGM) and diabetic retinopathy in type 1 and type 2 diabetes. Acta Diabetol 50: 437-442.
66. Sun ZJ, Yang YC, Wu JS, Wang MC, Chang CL, Lu FH, 2015 Increased risk of glomerular hyperfiltration in subjects with impaired glucose tolerance and newly diagnosed diabetes. Nephrol Dial Transplant 31: 1295-1301.
67. Lorenzo C, Hartnett S, Hanley AJ, Rewers MJ, Wagenknecht LE, Karter AJ, 2013 Impaired fasting glucose and impaired glucose tolerance have distinct lipoprotein and apolipoprotein changes: the insulin resistance atherosclerosis study. J Clin Endocrinol Metab 98: 1622-1630.
68. Monnier L, Lapinski H, Colette C, 2003 Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care 26: 881-885.
69. Woerle HJ, Neumann C, Zschau S, et al, 2007 Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract 77: 280-285.
70. Schernthaner G, Guerci B, Gallwitz B, et al, 2010 Impact of postprandial and fasting glucose concentrations on HbA1c in patients with type 2 diabetes. Diabetes Metab 36: 389-394.
71. Stensvold I, Tverdal A, Urdal P, Graff-Iversen S, 1993 Non-fasting serum triglyceride concentration and mortality from coronary heart disease and any cause in middle aged Norwegian women. BMJ 307: 1318-1322.
72. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM, 2007 Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 298: 309-316.
73. Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM. 1996 A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 276: 882-888.
74. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A, 2007 Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women JAMA 298: 299-308.
75. Nordestgaard BG, Freiberg JJ, 2011 Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol. Curr Vasc Pharmacol 9: 281-286.
76. Teno S, Uto Y, Nagashima H, et al, 2000 Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. Diabetes Care 23: 1401-1406.
77. Mori Y, Itoh Y, Komiya H, Tajima N, 2005 Association between postprandial remnant-like particle triglyceride (RLP-TG) levels and carotid intima-media thickness (IMT) in Japanese patients with type 2 diabetes: assessment by meal tolerance tests (MTT). Endocrine 28: 157-163.
78. Ahmad J, Hameed B, Das G, Siddiqui MA, Ahmad I, 2005 Postprandial hypertriglyceridemia and carotid intima-media thickness in north Indian type 2 diabetic subjects. Diabetes Res Clin Pract 69: 142-150.
79. Chen X, Tian H, Liu R, 2003 Association between fasting and postprandial triglyceride levels and carotid intima-media thickness in type 2 diabetes patients. Chin Med J (Engl) 116: 1933-1935.
80. Daskalova DC, Kolovou GD, Panagiotakos DB, Pilatis ND, Cokkinos DV, 2005 Increase in aortic pulse wave velocity is associated with abnormal postprandial triglyceride response. Clin Cardiol 28: 577-583.
81. Bureau C, Laurent J, Robic MA, et al, 2016 Central obesity is associated with non-cirrhotic portal vein thrombosis. J Hepatol 64: 427-432.
82. Papoutsakis C, Chondronikola M, Antonogeorgos G, et al, 2015 Associations between central obesity and asthma in children and adolescents: a case-control study. J Asthma 52: 128-134.
83. Capelo AV, De Fonseca VM, Peixoto MV, De Carvalho SR, Guerino LG, 2015 Central obesity and other factors associated with uncontrolled asthma in women. Allergy Asthma Clin Immunol 11: 12.
84. Pang Q, Zhang JY, Song SD, et al, 2015 Central obesity and nonalcoholic fatty liver disease risk after adjusting for body mass index. World J Gastroenterol 21: 1650-1662.
85. Beydoun MA, Beydoun HA, Wang Y, 2008 Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis. Obes Rev 9: 204-218.
86. Oka R, Kobayashi J, Miura K, Nagasawa S, Moriuchi T, Hifumi S, 2009 Difference between fasting and nonfasting triglyceridemia; the influence of waist circumference. J Atheroscler Thromb 16: 633-640.
87. Lacroix S, Rosiers CD, Tardif JC, Nigam A, 2012 The role of oxidative stress in postprandial endothelial dysfunction. Nutr Res Rev 25: 288-301.
88. Ceriello A, Taboga C, Tonutti L, et al, 2002 Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106: 1211-1218.
89. Lee IK, Kim HS, Bae JH, 2002 Endothelial dysfunction: its relationship with acute hyperglycaemia and hyperlipidemia. Int J Clin Pract Suppl 129: 59-64.
90. Esposito K, Nappo F, Marfella R, et al, 2002 Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 106: 2067-2072.
91. Nappo F, Esposito K, Cioffi M, et al, 2002 Postprandial endothelial activation in healthy subjects and in type 2 diabetic patients: Role of fat and carbohydrate meal. J Am Coll Cardiol 39: 1145-1150.
92. Ceriello A, Quagliaro L, Piconi L, et al, 2004 Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 53: 701-710.
93. Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J, 1998 Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet 351: 88-92.
94. Morisaki N, Saito I, Tamura K, et al, 1997 New indices of ischemic heart disease and aging: studies on the serum levels of soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular cell adhesion molecule-1 (VCAM-1) in patients with hypercholesterolemia and ischemic heart disease. Atherosclerosis 131: 43-48.
95. Peter K, Nawroth P, Conradt C, et al, 1997 Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. Arterioscler Thromb Vasc Biol 17: 505-512.
96. Motojima K, Azuma K, Kitahara Y, et al, 2008 Repetitive postprandial hypertriglyceridemia induces monocyte adhesion to aortic endothelial cells in Goto-Kakizaki rats. Endocr J 55: 373-379.
97. de Vries MA, Alipour A, Klop B, et al, 2015 Glucose-dependent leukocyte activation in patients with type 2 diabetes mellitus, familial combined hyperlipidemia and healthy controls. Metabolism 64: 213-217.
98. Santilli F, Formoso G, Sbraccia P, et al, 2010 Postprandial hyperglycemia is a determinant of platelet activation in early type 2 diabetes mellitus. J Thromb Haemost 8: 828-387.
99. Gresele P, Guglielmini G, De Angelis M, et al, 2003 Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus. J Am Coll Cardiol 41: 1013-1020.
100. Byrne CD, Wareham NJ, Martensz ND, Humphries SE, Metcalfe JC, Grainger DJ, 1998 Increased PAI activity and PAI-1 antigen occurring with an oral fat load: associations with PAI-1 genotype and plasma active TGF-beta levels. Atherosclerosis 140: 45-53.
101. Tholstrup T, Miller GJ, Bysted A, Sandström B, 2003 Effect of individual dietary fatty acids on postprandial activation of blood coagulation factor VII and fibrinolysis in healthy young men. Am J Clin Nutr 77: 1125-1132.
102. Coles N, Bremer K, Kives S, Zhao X, Hamilton J, 2016 Utility of the Oral Glucose Tolerance Test to Assess Glucose Abnormalities in Adolescents with Polycystic Ovary Syndrome. J Pediatr Adolesc Gynecol 29: 48-52.
103. Kyaw Tun T, McGowan A, Phelan N, et al, 2016 Obesity and insulin resistance are the main determinants of postprandial lipoprotein dysmetabolism in polycystic ovary syndrome. Int J Endocrinol 2016: 9545239.
104. Bahceci M, Aydemir M, Tuzcu A, 2007 Effects of oral fat and glucose tolerance test on serum lipid profile, apolipoprotein, and CRP concentration, and insulin resistance in patients with polycystic ovary syndrome. Fertil Steril 87: 1363-1368.
105. Diamanti-Kandarakis E, Xyrafis X, Boutzios G, Christakou C, 2008 Pancreatic beta-cells dysfunction in polycystic ovary syndrome. Panminerva Med 50: 315-325.
106. Economou F, Xyrafis X, Livadas S, et al, 2009 In overweight/obese but not in normal-weight women, polycystic ovary syndrome is associated with elevated liver enzymes compared to controls. Hormones (Athens) 8: 199-206.
107. Kimura Y, Hyogo H, Ishitobi T, Nabeshima Y, Arihiro K, Chayama K, 2011 Postprandial insulin secretion pattern is associated with histological severity in non-alcoholic fatty liver disease patients without prior known diabetes mellitus. J Gastroenterol Hepatol 26: 517-522.
108. Manchanayake J, Chitturi S, Nolan C, Farrell GC, 2011 Postprandial hyperinsulinemia is universal in non-diabetic patients with nonalcoholic fatty liver disease. J Gastroenterol Hepatol 26: 510-516.
109. Musso G, Gambino R, De Michieli F, et al, 2008 Association of liver disease with postprandial large intestinal triglyceride-rich lipoprotein accumulation and pro/antioxidant imbalance in normolipidemic non-alcoholic steatohepatitis. Ann Med 40: 383-394.
110. Matikainen N, Taskinen MR, Stennabb S, et al, 2012 Decrease in circulating fibroblast growth factor 21 after an oral fat load is related to postprandial triglyceride-rich lipoproteins and liver fat. Eur J Endocrinol 166: 487-492.
111. American Diabetes Association, 2016 Standards of medical care in diabetes. Diabetes Care 38: 1-94.
112. International Diabetes Federation Guideline Development Group, 2014 Guideline for management of postmeal glucose in diabetes. Diabetes Res Clin Pract 103: 256-268.
113. Stettler C, Stahl M, Allemann S, et al, 2008 Association of 1,5-anhydroglucitol and 2-h postprandial blood glucose in type 2 diabetic patients. Diabetes Care 31: 1534-1535.
114. Seok H, Huh JH, Kim HM, et al, 2015 1,5-anhydroglucitol as a useful marker for assessing short-term glycemic excursions in type 1 diabetes. Diabetes Metab J 39: 164-170.
115. Berglund L, Brunzell JD, Goldberg AC, et al, 2012 Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97: 2969-2989.
116. Jellinger PS, Smith DA, Mehta AE, et al, AACE Task Force for Management of Dyslipidemia and Prevention of Atherosclerosis, 2012 American Association of Clinical Endocrinologists’ Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis: Executive summary. Endocr Pract 18: 269-293.
117. Su JW, Nzekwu MM, Cabezas MC, et al, 2009 Methods to assess impaired post-prandial metabolism and the impact for early detection of cardiovascular disease risk. Eur J Clin Invest 39: 741-754.
118. Nagata T, Sugiyama D, Kise T, et al, 2012 Fasting remnant lipoproteins can predict postprandial hyperlipidemia. Lipids Health Dis 11: 146.
119. White KT, Moorthy MV, Akinkuolie AO, et al, 2015 Identifying an optimal cutpoint for the diagnosis of hypertriglyceridemia in the nonfasting state. Clin Chem 61: 1156-1163.
120. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, 2013 Targets for glycemic control. Can J Diabetes 37 Suppl 1: 31-34.
121. Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC); European Association for the Study of Diabetes (EASD), Rydén L, Grant PJ, Anker SD, et al, 2014 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD - summary. Diab Vasc Dis Res 11: 133-173.
122. O’Keefe JH, Gheewala NM, O’Keefe JO, 2008 Dietary strategies for improving post-prandial glucose, lipids, inflammation, and cardiovascular health. J Am Coll Cardiol 51: 249-255.
123. Hollekim-Strand SM, Malmo V, Follestad T, Wisløff U, Ingul CB, 2015 Fast food increases postprandial cardiac workload in type 2 diabetes independent of pre-exercise: A pilot study. Nutr J 14: 79.
124. De Natale C, Annuzzi G, Bozzetto L, et al, 2009 Effects of a plant-based high-carbohydrate/high-fiber diet versus high-monounsaturated fat/low-carbohydrate diet on postprandial lipids in type 2 diabetic patients. Diabetes Care 32: 2168-2173.
125. Giacco R, Costabile G, Della Pepa G, et al, 2014 A whole-grain cereal-based diet lowers postprandial plasma insulin and triglyceride levels in individuals with metabolic syndrome. Nutr Metab Cardiovasc Dis 24: 837-844.
126. Dandona P, Ghanim H, Abuaysheh S, et al, 2015 Decreased insulin secretion and incretin concentrations and increased glucagon concentrations after a high-fat meal when compared with a high-fruit and -fiber meal. Am J Physiol Endocrinol Metab 308: E185-191.
127. Rizkalla SW, Taghrid L, Laromiguiere M, et al, 2004 Improved plasma glucose control, whole-body glucose utilization, and lipid profile on a low-glycemic index diet in type 2 diabetic men: a randomized controlled trial. Diabetes Care 27: 1866-1872.
128. Monro JA, Shaw M, 2008 Glycemic impact, glycemic glucose equivalents, glycemic index, and glycemic load: definitions, distinctions, and implications. Am J Clin Nutr 87: Suppl: 237-243.
129. Jenkins DJ, Wolever TM, Taylor RH, et al, 1981 Glycemic index of foods: a physiologic al basis for carbohydrate exchange. Am J Clin Nutr 34: 362-366.
130. Kang X, Wang C, Lifang L, et al, 2013 Effects of different proportion of carbohydrate in breakfast on postprandial glucose excursion in normal glucose tolerance and impaired glucose regulation subjects. Diabetes Technol Ther 15: 569-574.
131. Miyoshi T, Noda Y, Ohno , et al, 2014 Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals - a randomized cross-over trial. Biomed Pharmacother 68: 1071-1077.
132. Wong AT, Chan DC, Barrett PH, Adams LA, Watts GF, 2014 Effect of ω-3 fatty acid ethyl esters on apolipoprotein B-48 kinetics in obese subjects on a weight-loss diet: a new tracer kinetic study in the postprandial state. J Clin Endocrinol Metab 99: E1427-1435.
133. Hedengran A, Szecsi PB, Dyerberg J, Harris WS, Stender S, 2015 n-3 PUFA esterified to glycerol or as ethyl esters reduce non-fasting plasma triacylglycerol in subjects with hypertriglyceridemia: a randomized trial. Lipids 50: 165-175.
134. Park YM, Heden TD, Liu Y, et al, 2015 A high-protein breakfast induces greater insulin and glucose-dependent insulinotropic peptide responses to a subsequent lunch meal in individuals with type 2 diabetes. J Nutr 145: 452-458.
135. Mamo JC, James AP, Soares MJ, Griffiths DG, Purcell K, Schwenke JL, 2005 A low-protein diet exacerbates postprandial chylomicron concentration in moderately dyslipidaemic subjects in comparison to a lean red meat protein-enriched diet. Eur J Clin Nutr 59: 1142-1148.
136. MacLeod SF, Terada T, Chahal BS, Boulé NG, 2013 Exercise lowers postprandial glucose but not fasting glucose in type 2 diabetes: a meta-analysis of studies using continuous glucose monitoring. Diabetes Metab Res Rev 29: 593-603.
137. Mitchell JB, Rowe JR, Shah M, Barbee JJ, Watkins AM, Stephens C, 2008 Effect of prior exercise on postprandial triglycerides in overweight young women after ingesting a high-carbohydrate meal. Int J Sport Nutr Exerc Metab 18: 49-65.
138. Zhang JQ, Ji LL, Fogt DL, Fretwell VS, 1985 Effect of exercise duration on postprandial hypertriglyceridemia in men with metabolic syndrome. J Appl Physiol 103: 1339-1345.
139. Tobin LW, Kiens B, Galbo H, 2008 The effect of exercise on postprandial lipidemia in type 2 diabetic patients. Eur J Appl Physiol 102: 361-370.
140. Koehestanie P, de Jonge C, Berends FJ, Janssen IM, Bouvy ND, Greve JW, 2014 The effect of the endoscopic duodenal-jejunal bypass liner on obesity and type 2 diabetes mellitus, a multicenter randomized controlled trial. Ann Surg 260: 984-992.
141. Baskota A, Li S, Dhakal N, Liu G, Tian H, 2015 Bariatric surgery for type 2 diabetes mellitus in patients with BMI <30 kg/m2: A systematic review and meta-analysis. PLoS One 10: e0132335.
142. DiNicolantonio JJ, Bhutani J, O’Keefe JH, 2015 Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes. Open Heart 2: e000327.
143. Kato T, Node K, 2014 Therapeutic potential of α-glucosidase inhibitors to prevent postprandial endothelial dysfunction. Int Heart J 55: 386-390.
144. Aleskow Stein S, Lamos EM, Davis SN, 2012 A review of the efficacy and safety of oral antidiabetic drugs. Expert Opin Drug Saf 12: 153-175.
145. Rosenstock J, Hassman DR, Madder RD, et al, 2004 Repaglinide versus nateglinide monotherapy: a randomized, multicenter study. Diabetes Care 27: 1265-1270.
146. Esposito K, Giugliano D, Nappo F, Marfella R; Campanian Postprandial Hyperglycemia Study Group, 2004 Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation 110: 214-219.
147. Werner U, 2014 Effects of the GLP1 receptor agonist lixisenatide on postprandial glucose and gastric emptying-preclinical evidence. J Diabetes Complications 28: 110-114.
148. Cervera A1, Wajcberg E, Sriwijitkamol A, et al, 2008 Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab 294: E846-852.
149. Pfeffer MA, Claggett B, Diaz R, et al, 2015 Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med 373: 2247-2257.
150. Marso SP, Daniels GH, Brown-Frandsen K, et al, 2016 Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 375: 311-322.
151. Godinho R, Mega C, Teixeira-de-Lemos E, et al, 2015 The place of dipeptidyl peptidase-4 inhibitors in type 2 diabetes therapeutics: A «me too» or «the special one» antidiabetic class? J Diabetes Res 2015: 806979.
152. Tanimoto M, Kanazawa A, Hirose T, et al, 2015 Comparison of sitagliptin with nateglinide on postprandial glucose and related hormones in drug-naïve Japanese patients with type 2 diabetes mellitus: A pilot study. J Diabetes Investig 6: 560-566.
153. Ryan G, Briscoe TA, Jobe, 2009 Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes. Drug Des Devel Ther 2: 203-214.
154. European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL, De Backer G, et al, 2011 ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 32: 1769-1818.
155. Kolovou GD, Anagnostopoulou KK, Salpea KD, Daskalopoulou SS, Mikhailidis DP. 2007 The effect of statins on postprandial lipemia. Curr Drug Targets 8: 551-560.
156. Parhofer KG, Laubach E, Barrett PH, 2003 Effect of atorvastatin on postprandial lipoprotein metabolism in hypertriglyceridemic patients. J Lipid Res 44: 1192-1198.
157. Arao K, Yasu T, Umemoto T, et al, 2009 Effects of pitavastatin on fasting and postprandial endothelial function and blood rheology in patients with stable coronary artery disease. Circ J 73: 1523-1530.
158. Nagashima H, Endo M, 2011 Pitavastatin prevents postprandial endothelial dysfunction via reduction of the serum triglyceride level in obese male subjects. Heart Vessels 26: 428-434.
159. Hajer GR, Dallinga-Thie GM, van Vark-van der Zee LC, Visseren FL, 2009 The effect of statin alone or in combination with ezetimibe on postprandial lipoprotein composition in obese metabolic syndrome patients. Atherosclerosis 202: 216-224.
160. Kikuchi K, Nezu U, Inazumi K, et al, 2012 Double-blind randomized clinical trial of the effects of ezetimibe on postprandial hyperlipidaemia and hyperglycaemia. J Atheroscler Thromb 19: 1093-1101.
161. Hiramitsu S, Miyagishima K, Ishii J, et al, 2012 Effect of ezetimibe on lipid and glucose metabolism after a fat and glucose load. J Cardiol 60: 395-400.
162. Bozzetto L, Annuzzi G, Corte GD, et al, 2011 Ezetimibe beneficially influences fasting and postprandial triglyceride-rich lipoproteins in type 2 diabetes. Atherosclerosis 217: 142-148.
163. Yunoki K, Nakamura K, Miyoshi T, et al, 2011 Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction. Atherosclerosis 217: 486-491.
164. Westerink J, Deanfield JE, Imholz BP, et al, 2013 High-dose statin monotherapy versus low-dose statin/ezetimibe combination on fasting and postprandial lipids and endothelial function in obese patients with the metabolic syndrome: The PANACEA study. Atherosclerosis 227: 118-124.
165. Kolovou GD, Kostakou PM, Anagnostopoulou KK, Cokkinos DV, 2008 Therapeutic effects of fibrates in postprandial lipemia. Am J Cardiovasc Drugs 8: 243-255.
166. Rosenson RS, Wolff DA, Huskin AL, Helenowski IB, Rademaker AW, 2007 Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome. Diabetes Care 30: 1945-1951.
167. Sharifi F, Hojeghani N, Mazloomzadeh S, Shajari Z, 2013 The efficacy of ezetimibe added to ongoing fibrate-statin therapy on postprandial lipid profile in the patients with type 2 diabetes mellitus. J Diabetes Metab Disord 12: 24.
168. The ACCORD Study Group, 2010 Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 362: 1563-1574.
169. Reyes-Soffer G, Ngai CI, Lovato L, et al, 2013 Effect of combination therapy with fenofibrate and simvastatin on postprandial lipemia in the ACCORD lipid trial. Diabetes Care 36: 422-428.

Address for correspondence:
Evanthia Diamanti-Kandarakis, 7 Athanasiadou Str., 115 21 Athens, Greece; Tel.: +30 2106416723, Fax: +30 2106416661, E-mail: e.diamanti.kandarakis@gmail.com

Received: 25-04-2016, Accepted: 15-09-2016