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World J Diabetes. Jul 10, 2015; 6(7): 970-977
Published online Jul 10, 2015. doi: 10.4239/wjd.v6.i7.970
Dyslipidaemia of diabetes and the intestine
Gerald H Tomkin, Daphne Owens
Gerald H Tomkin, Daphne Owens, Beacon Hospital Sandyford and Trinity College, Dublin 2, Ireland
Author contributions: Both authors contributed to this manuscript.
Conflict-of-interest statement: Neither Gerald H Tomkin nor Daphne Owens has any conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gerald H Tomkin, Professor, Beacon Hospital Sandyford and Trinity College, Clontra, Quinns Road, Shankill, Co Dublin, Dublin 2, Ireland. gerald.tomkin@tcd.ie
Telephone: +353-1-2390658 Fax: +353-1-2721395
Received: September 12, 2014
Peer-review started: September 13, 2014
First decision: December 12, 2014
Revised: February 11, 2015
Accepted: March 5, 2015
Article in press: March 9, 2015
Published online: July 10, 2015
Abstract

Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care. In particular the economic burden is growing at an alarming rate in parallel with the increasing world-wide prevalence of diabetes. The major disturbance of lipid metabolism in diabetes relates to the effect of insulin on fat metabolism. Raised triglycerides being the hallmark of uncontrolled diabetes, i.e., in the presence of hyperglycaemia. The explosion of type 2 diabetes has generated increasing interest on the aetiology of atherosclerosis in diabetic patients. The importance of the atherogenic properties of triglyceride rich lipoproteins has only recently been recognised by the majority of diabetologists and cardiologists even though experimental evidence has been strong for many years. In the post-prandial phase 50% of triglyceride rich lipoproteins come from chylomicrons produced in the intestine. Recent evidence has secured the chylomicron as a major player in the atherogenic process. In diabetes chylomicron production is increased through disturbance in cholesterol absorption, in particular Neimann Pick C1-like1 activity is increased as is intestinal synthesis of cholesterol through 3-hydroxy-3-methyl glutaryl co enzyme A reductase. ATP binding cassette proteins G5 and G8 which regulate cholesterol in the intestine is reduced leading to chylomicronaemia. The chylomicron particle itself is atherogenic but the increase in the triglyceride-rich lipoproteins lead to an atherogenic low density lipoprotein and low high density lipoprotein. The various steps in the absorption process and the disturbance in chylomicron synthesis are discussed.

Keywords: Triglyceride, Cholesterol chylomicrons, Microsomal triglyceride transfer protein, Niemann Pick C1-like1, Lipoproteins, Diabetes, ATP binding cassette proteins G5/G8

Core tip: The explosion of type 2 diabetes has generated increasing interest on the aetiology of atherosclerosis in diabetic patients. Evidence is mounting on the importance of the atherogenic properties of triglyceride rich lipoproteins. In the post-prandial phase 50% of triglyceride rich lipoproteins come from chylomicrons produced in the intestine. Recent evidence has secured the chylomicron as a major player in the atherogenic process. In diabetes chylomicron production is increased through disturbance in cholesterol absorption. This paper reviews recent literature in relation to diabetes, the intestine and dyslipidaemia with a view to understanding new targets for treatment.