The intestine as a regulator of cholesterol homeostasis in diabetes
Diabetes Institute of Ireland, Beacon Clinic Dublin, and Blackrock Clinic Dublin, Department of Medicine, Trinity College, Dublin, Ireland. Atherosclerosis Supplements
(Impact Factor: 2.29).
09/2008; 9(2):27-32. DOI: 10.1016/j.atherosclerosissup.2008.05.012
The chylomicron influences very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) composition but itself is atherogenic. Thus abnormalities of chylomicron production are of interest particularly in conditions such as diabetes which confer major cardiovascular risk. Intestinal function is abnormal in diabetes and is a major cause of the dyslipidaemia found in this condition. Studies have suggested that cholesterol absorption is decreased in diabetes and cholesterol synthesis increased. Molecular mechanisms involved in insulin resistance in the intestine and its effect on cholesterol homeostasis in diabetes are described. Abnormalities in triglyceride synthesis and alterations genes regulating cholesterol absorption and intestinal synthesis are discussed. In particular, increase in apolipoprotein B48 synthesis has been demonstrated in animal models of diabetes and insulin resistance. Intestinal mRNA expression of Niemann Pick C1-like 1, protein is increased in both experimental and human diabetes suggesting that an increase in cholesterol transportation does occur. mRNA expression of the ATP binding cassette proteins (ABC) G5 and G8, two proteins working in tandem to excrete cholesterol have been shown to be decreased suggesting increased delivery of cholesterol for absorption. Expression of microsomal triglyceride transfer protein, which assembles the chylomicron particle, is increased in diabetes leading to increase in both number and cholesterol content. In conclusion, diabetes is associated with considerable dysfunction of the intestine leading to abnormal chylomicron composition which may play a major part in the premature development of atherosclerosis.
Available from: Kathleen M Botham
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ABSTRACT: Postprandial lipemia is the transient increase in blood lipids which occurs after a meal containing fat and is caused by raised levels of triglyceride-rich lipoproteins (TRLs) in the blood. Delayed clearance of TRLs leads to post-prandial hyperlipidemia, and there is now a great deal of evidence to support the idea that this condition is an important risk factor for cardiovascular disease (CVD). Western lifestyle habits including: diets low in fresh fruit and vegetables and high in fat and processed food, alcohol consumption, smoking, and lack of exercise tend to promote postprandial hyperlip-idemia, and it is a characteristic feature of increasingly common metabolic diseases such as obesity, insulin resistance and type 2 diabetes which are also linked to modern lifestyle behaviour and which carry an increased risk of CVD develop-ment. Modification of lifestyle factors such as changing to a healthier diet, weight loss, reducing alcohol consumption and increasing exercise can cause significant reductions in postprandial hyperlipidemia and thus help to reduce this risk. De-spite the growing recognition that the extent of postprandial lipemia is a good predictor of CVD, no standardized method-ology for its measurement is currently available. Determination of blood TG levels after consumption of a standard test meal is likely to be the most convenient approach for a routine clinical test, and we propose a standard test meal which is easily adaptable for the variations in dietary habits in different countries. Greater use of postprandial lipid determination will aid in the translation of our extensive knowledge on the role of nutrition in health into national and international pol-icy.
The Open Translational Medicine Journal 04/2010; 2(1). DOI:10.2174/1876399501002010001
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ABSTRACT: Diabetes mellitus is a worldwide epidemic with high mortality. As concern over this disease rises, the number and value of research grants awarded by the National Research Foundation of Korea (NRF) have increased. Diabetes mellitus is classified into two groups. Type 1 diabetes requires insulin treatment, whereas type 2 diabetes, which is characterized by insulin resistance, can be treated using a variety of therapeutic approaches. Hyperglycemia is thought to be a primary factor in the onset of diabetes, although hyperlipidemia also plays a role. The major organs active in the regulation of blood glucose are the pancreas, liver, skeletal muscle, adipose tissue, intestine, and kidney. Diabetic complications are generally classified as macrovascular (e.g., stroke and heart disease) or microvascular (i.e., diabetic neuropathy, nephropathy, and retinopathy). Several animal models of diabetes have been used to develop oral therapeutic agents, including sulfonylureas, biguanides, thiazolidinediones, acarbose, and miglitol, for both type 1 and type 2 diseases. This review provides an overview of diabetes mellitus, describes oral therapeutic agents for diabetes and their targets, and discusses new developments in diabetic drug research.
Asian Australasian Journal of Animal Sciences 05/2010; 23(5). DOI:10.5713/ajas.2010.90637 · 0.54 Impact Factor
Available from: Maurizio Averna
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ABSTRACT: This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high-risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy.
Patients (n = 618) at high risk for coronary vascular disease with elevated LDL-C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double-blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among patients with (n = 182) and without T2DM (n = 434).
EZE/SIMVA was more effective than ROSUVA at lowering LDL-C, TC, non-HDL-C, and apo B in the overall study population and within both subgroups. Numerically, greater between-treatment reductions in LDL-C, TC, non-HDL-C, and apo B were seen in patients with T2DM versus those without T2DM. A significant interaction (P= 0.015) was seen for LDL-C indicating that patients with T2DM achieved larger between-group reductions versus those without T2DM.
Switching to EZE/SIMVA 10/20 mg versus ROSUVA 10 mg provided superior lipid reductions in patients with/without T2DM.
Cardiovascular Therapeutics 07/2010; 30(2):61-74. DOI:10.1111/j.1755-5922.2010.00181.x · 2.36 Impact Factor
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