To test whether there is an association between fasting ApoB48 level, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic, and peripheral artery disease (PAD) in type 2 diabetic patients independent of fasting plasma lipids.
We studied 87 patients with type 2 diabetes: 34 with asymptomatic PAD (ankle/brachial index < 0.9) and 53 without PAD matched on age (±2 years), gender and BMI (±2 kg/m(2)). The plasma fasting ApoB48 was measured by ELISA.
Patients with PAD had significantly higher ApoB48 levels (1.529 ± 1.253 vs 1.095 ± 0.667 μg/ml p = 0.04) than those without PAD independent of major confounders, such as duration of diabetes, smoking status, HbA1c, systolic blood pressure and fasting plasma lipids.
Fasting ApoB48 was independently associated with asymptomatic PAD in patients with type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Overproduction of hepatic apoB100-containing VLDL particles has been well documented in animal models and in humans with insulin resistance such as the metabolic syndrome and type 2 diabetes, and contributes to the typical dyslipidemia of these conditions. In addition, postprandial hyperlipidemia and elevated plasma concentrations of intestinal apoB48-containing chylomicron and chylomicron remnant particles have been demonstrated in insulin resistant states. Intestinal lipoprotein production is primarily determined by the amount of fat ingested and absorbed. Until approximately 10 years ago, however, relatively little attention was paid to the role of the intestine itself in regulating the production of triglyceride-rich lipoproteins (TRL) and its dysregulation in pathological states such as insulin resistance. We and others have shown that insulin resistant animal models and humans are characterized by overproduction of intestinal apoB48-containing lipoproteins. Whereas various factors are known to regulate hepatic lipoprotein particle production, less is known about factors that regulate the production of intestinal lipoprotein particles. Monosacharides, plasma free fatty acids (FFA), resveratrol, intestinal peptides (e.g. GLP-1 and GLP-2), and pancreatic hormones (e.g. insulin) have recently been shown to be important regulators of intestinal lipoprotein secretion. Available evidence in humans and animal models strongly supports the concept that the small intestine is not merely an absorptive organ but rather plays an active role in regulating the rate of production of chylomicrons in fed and fasting states. Metabolic signals in insulin resistance and type 2 diabetes and in some cases an aberrant intestinal response to these factors contribute to the enhanced formation and secretion of TRL. Understanding the regulation of intestinal lipoprotein production is imperative for the development of new therapeutic strategies for the prevention and treatment of dyslipidemia. Here we review recent developments in this field and present evidence that intestinal lipoprotein production is a process with metabolic plasticity and that modulation of intestinal lipoprotein secretion may be a feasible therapeutic strategy in the treatment of dyslipidemia and possibly prevention of atherosclerosis.
[Show abstract][Hide abstract] ABSTRACT: Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus. Several reasons exist for peripheral arterial disease in diabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type 2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally, the use of certain specific postprandial particle markers, such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles.
[Show abstract][Hide abstract] ABSTRACT: The intestine must challenge the profuse daily flux of dietary fat that serves as a vital source of energy and as an essential component of cell membranes. The fat absorption process takes place in a series of orderly and interrelated steps, including the uptake and translocation of lipolytic products from the brush border membrane to the endoplasmic reticulum, lipid esterification, apolipoprotein (Apo) synthesis and ultimately the packaging of lipid and Apo components into chylomicrons (CM). Deciphering inherited disorders of intracellular CM elaboration afforded new insight into the key functions of crucial intracellular proteins, such as Apo B, microsomal triglyceride transfer protein and Sar1B GTPase, the defects of which lead to hypobetalipoproteinemia, abetalipoproteinemia, and chylomicron retention disease, respectively. These experiments of nature are characterized by fat malabsorption, steatorrhea, failure to thrive, low levels of triglycerides and cholesterol, and deficiency of liposoluble vitamins and essential fatty acids. After summarizing and discussing the functions and regulation of these proteins for reader's comprehension, the current review focuses on their specific roles in malabsorptions and dyslipidemia-related intestinal fat hyperabsorption while dissecting the spectrum of clinical manifestations and managements. The influence of newly discovered proteins (PCSK9 and ANGPTL3) on fat absorption has also been provided. Finally, it was stressed how the overexpression or polymorphisms status of the critical intracellular proteins promotes dyslipidemia and cardiometaboloic disorders.
The Journal of Lipid Research 11/2014; 56(5). DOI:10.1194/jlr.R052415 · 4.42 Impact Factor
Philip Babatunde Adebayo, Adeseye Abiodun Akintunde, Morenike Bosede Audu, Olugbenga Edward Ayodele, Rufus Olushola Akinyemi, Oladimeji George Opadijo
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