Dyslipidaemia of diabetes and the intestine

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.