Determinants of uncontrolled dyslipidaemia among adult type 2 diabetes in Malaysia: The Malaysian Diabetes Registry 2009
Original Research Article
Diabetes Research and Clinical Practice, Volume 96, Issue 3, June 2012, Pages 339-347
Boon How Chew*, Mastura Ismail, Ping Yein Lee, Sri Wahyu Taher, Jamaiyah Haniff, Feisul Idzwan Mustapha, Mohd Adam Bujang
* Corresponding author at: Department of Family Medicine, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia. Tel.: +60 3 89472520; fax: +60 3 89472328.
E-mail address: chewboonhow@yahoo.com (B.H. Chew).
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What is CAD?
CAD is the most common complication and a major cause of mortality in T2DM (type 2 diabetes mellitus). Patients with T2DM have a higher prevalence of small and dense LDL particles, which are more susceptible to oxidation (ie become oxLDL), therefore increasing atherogenic risk (high oxLDL, high risk CAD) even when there is not a high concentration of LDL cholesterol. This is true of the Indians who usually have low LDL-C but still have high risk for CAD.
What is LDL-C?
LDL cholesterol (LDL-C) is a measure of the cholesterol carrying capacity of the lipoprotein constituents in blood. Generally, a high total cholesterol (high TC) correlates with a high LDL-C. When LDL-C is high, the opposite occurs to HDL-C. When LDL-C is high, HDL-C is low and this is true is most populations which have been studied except in the Indians. In the case with Indians, they have low LDL-C and low HDL-C. The low HDL-C generally is attributed to endothelial dysfunction, a prerequisite for atherosclerosis and impending CAD. So when we detect Indians with low LDL-C and low HDL-C, it is a tell tale sign and hallmark of an impending CAD. There is no doubt about it.
What is HDL-C?
If LDL carry cholesterol to peripheral tissues (extrahepatic tissues, ie not the liver; tissues apart from the liver), the HDL carry excess cholesterol in the reverse direction, ie back to the liver. For this role, HDL activity is described as reverse cholesterol transport (RCT). What can go wrong with HDL activity. HDL formation and cholesterol uptake are significant initial steps in RCT. When there is prolonged lipaemia, LPL activity is arrested (inhibited). So very little nascent HDL are formed by lipolysis (the other sources of HDL being hepatic production and intestinal production).
When there is disruption to the endothelial surface, cholesterol efflux is affected (less efficient or inefficient). Because choleserol uptake by nascent discoidal HDL is affected, HDL cannot 'grow big', ie they cannot imbibe the excess cholesterol from endothelial cells. Hence, these nascent or small HDL do not contain sufficient cholesterol for the next step to occur - cholesterol esterification by an enzyme called lecithin:cholesterol acyltransferase (LCAT). We must remember that the spherical structure of HDL itself is only possible when the ratio of its lipid components is correct (there is a formula for this). Otherwise the HDL remain discoidal (flattened) and not spherical. Since LCAT activity is limited, the HDL size cannot grow and thus it should be expected there would be a lot of tiny HDL particles in those who have high risk of CAD.
What lipid ratios and indices or combinations are safe or unsafe?
There are so many reports and findings today, which have not been properly tabulated for easy reference. It takes a lot of knowledge to understand what the data means and to be able to interpret correctly. It does take practice and every case is different. Generally,
- high LDL-C: high risk CAD
- high HDL-C: low risk CAD
- high LDL-C, low HDL-C: high risk CAD
- low-C, low HDL-C: high risk CAD
- diabetics: high risk CAD
- diabetic dyslipidaemia: high risk CAD
What is diabetic dyslipidaemia?
When lipaemia is prolonged, a lot of things go wrong intravascularly (in the blood itself). In diabetics, there is prolonged lipaemia; the blood does not rapidly clear up after we eat. Why? This is because a lot of the apparatus to clear up the blood has gone bonkers. I'm talking about lipolysis by lipoprotein liase (LPL). Because of prolonged lipaemia, it gives time for LDL to transform to very small and dense particles called small dense LDL. These little particles are dangerous not only because of their tiny sizes but because they are prone to oxidation. Tiny LDL are oxidised to oxLDL. Tiny LDL can penetrate the arterial intima and lodge in the underlying tissues. They are oxidised and gorged by macrophages. The oxLDL maybe gone but the macrophages now become laden and die to become foam cells. That is the beginning of all the problems related to arterial stiffening etc. Then CAD is the ultimate happening.
