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Elevated Endothelial Microparticles Following Consecutive Meals Are Associated With Vascular Endothelial Dysfunction in Type 2 Diabetes

Maarten E. Tushuizen, Rienk Nieuwland, Cees Rustemeijer, Bert E. Hensgens, Augueste Sturk, Robert J. Heine, Michaëla Diamant

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Abstract

T ype 2 diabetes is associated withprolonged and exaggerated post-prandial hyperglycemia and hyper-triglyceridemia, endothelial dysfunction, and cardiovascular disease (CVD) (1–7). Endothelial dysfunction may link post-prandial dysmetabolism to CVD (5–7). Since the postprandial state unveils the full scope of metabolic abnormalities in type 2 diabetes, previous studies (1) in fasting subjects may have underestimated the true risk. Currently, endothelial func-tions can only be estimated from indirect measurements, such as flow-mediated di-lation (FMD) (6,8). Cell-derived microparticles are re-leased by cells in response to stress. In-creased numbers of microparticles of various cellular origin circulate in patients at risk of CVD (9,10). Recently, vascular-endothelial cadherin (CD144)-positive microparticles were demon-strated in type 2 diabetic patients with coronary artery disease and patients with end-stage renal disease (11,12). Since vascular-endothelial cadherin is exclu-sively expressed by endothelial cells, CD144-positive microparticles may be regarded as endothelium-derived micro-particles (EMPs), directly reflecting endo-thelial damage. However, it is unknown whether circulating EMPs are cause or consequence of CVD, and whether their occurrence associates with CVD per se or, rather, with diabetes-related metabolic abnormalities. We hypothesized that in patients with uncomplicated type 2 diabetes, exposure to three consecutive high-fat mixed meals, given during a 24-h period, will disclose the full scope of their compro-mised metabolism and subsequent endo-thelial dysfunction, measured as FMD and circulating EMPs.

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What this paper is about

T ype 2 diabetes is associated withprolonged and exaggerated post-prandial hyperglycemia and hyper-triglyceridemia, endothelial dysfunction, and cardiovascular disease (CVD) (1–7). Endothelial dysfunction may link post-prandial dysmetabolism to CVD (5–7). Since the postprandial state unveils the full scope of metabolic abnormalities in type 2 diabetes, previous studies (1) in fasting subjects may have underestimated the true risk. Currently, endothelial func-tions can only be estimated from indirect measurements, such as flow-mediated di-lation (FMD) (6,8). Cell-derived microparticles are re-leased by cells in response to stress. In-creased numbers of microparticles of various cellular origin circulate in patients at risk of CVD (9,10). Recently, vascular-endothelial cadherin (CD144)-positive microparticles were demon-strated in type 2 diabetic patients with coronary artery disease and patients with end-stage renal disease (11,12). Since vascular-endothelial cadherin is exclu-sively expressed by endothelial cells, CD144-positive microparticles may be regarded as endothelium-derived micro-particles (EMPs), directly reflecting endo-thelial damage. However, it is unknown whether circulating EMPs are cause or consequence of CVD, and whether their occurrence associates with CVD per se or, rather, with diabetes-related metabolic abnormalities. We hypothesized that in patients with uncomplicated type 2 diabetes, exposure to three consecutive high-fat mixed meals, given during a 24-h period, will disclose the full scope of their compro-mised metabolism and subsequent endo-thelial dysfunction, measured as FMD and circulating EMPs.

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Available abstract

T ype 2 diabetes is associated withprolonged and exaggerated post-prandial hyperglycemia and hyper-triglyceridemia, endothelial dysfunction, and cardiovascular disease (CVD) (1–7). Endothelial dysfunction may link post-prandial dysmetabolism to CVD (5–7). Since the postprandial state unveils the full scope of metabolic abnormalities in type 2 diabetes, previous studies (1) in fasting subjects may have underestimated the true risk. Currently, endothelial func-tions can only be estimated from indirect measurements, such as flow-mediated di-lation (FMD) (6,8). Cell-derived microparticles are re-leased by cells in response to stress. In-creased numbers of microparticles of various cellular origin circulate in patients at risk of CVD (9,10). Recently, vascular-endothelial cadherin (CD144)-positive microparticles were demon-strated in type 2 diabetic patients with coronary artery disease and patients with end-stage renal disease (11,12). Since vascular-endothelial cadherin is exclu-sively expressed by endothelial cells, CD144-positive microparticles may be regarded as endothelium-derived micro-particles (EMPs), directly reflecting endo-thelial damage. However, it is unknown whether circulating EMPs are cause or consequence of CVD, and whether their occurrence associates with CVD per se or, rather, with diabetes-related metabolic abnormalities. We hypothesized that in patients with uncomplicated type 2 diabetes, exposure to three consecutive high-fat mixed meals, given during a 24-h period, will disclose the full scope of their compro-mised metabolism and subsequent endo-thelial dysfunction, measured as FMD and circulating EMPs.

Key concepts: Medicine, Endothelial dysfunction, Type 2 diabetes, Postprandial, Diabetes mellitus, Internal medicine, Endothelium, Coronary artery disease

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