Lipoprotein abnormalities associated with diabetes

Diabetes is associated with multiple disturbances in lipoprotein metabolism that are triggered by insulin deficiency, insulin resistance, and hyperglycemia [6,7]. The diabetic dyslipidemia of type 2 diabetes and insulin resistance is characterized several interrelated abnormalities, including triglyceride-rich lipoproteins (very low density lipoprotein [VLDL], intermediate density lipoprotein [IDL], and remnant particles), low high-density lipoprotein (HDL) cholesterol, and small, dense low-density lipoprotein (LDL) particles. There is an increase in the lipid-rich, large VLDL; upregulation of hepatic sterol regulatory element binding protein-1, which stimulates de novo lipid synthesis; and increased availability of free fatty acids, all of which probably are linked with insulin resistance [7]. The activity of lipoprotein lipase is suppressed which leads to reduced catabolism of triglyceride-rich particles, whereas hepatic lipase activity is increased which facilitates the compositional changes in LDL and HDL particles. Moreover, there is enhanced activity of cholesterol-ester transfer protein which mediates the transfer of triglyceride to LDL and HDL while cholesterol-esters from the latter are shunted to the larger triglyceride-rich particles. Thus, hypertriglyceride-mia is linked indirectly with changes in the HDL and LDL composition and associated with increased atherogenesis. The small, dense LDL

particles: (1) bind to intimal proteoglycans more avidly, (2) are more susceptible to oxidation and glycation, and (3) have impaired binding to LDL receptors; all of these factors contribute to the enhanced atherosclerosis in patients who have type 2 diabetes.

In a recent study, lipoprotein particle size and concentrations were characterized by nuclear magnetic resonance in subjects who had type 2 diabetes and normal or impaired insulin sensitivity that was characterized by euglycemic, hyper-insulinemic clamp technique [8]. There was a progressive increase in the size of VLDL particles in patients who were insulin sensitive, insulin resistant, and had type 2 diabetes and a reciprocal decrease in the size of LDL and HDL particles. Conversely, the cholesterol content in large LDL was decreased; the cholesterol content in small LDL was increased in patients who had insulin resistance and type 2 diabetes; and the calculated LDL cholesterol was unchanged, despite increased LDL particle number.

In view of the compositional changes in lipo-proteins, the LDL cholesterol that is determined in routine assays tends to underestimate the LDL particle number, particularly in patients who have hypertriglyceridemia [9,10]. Therefore, it was proposed that the direct measurement of apolipopro-tein B (apoB) may provide a better estimate of risk in such patients [11]; however, the assays for apoB are not well-standardized and are not widely available. An alternative that was proposed by ATPIII is the calculation of non-HDL cholesterol which estimates the cholesterol content in all atherogenic particles (VLDL, IDL, remnants, LDL, and lipoprotein [LP(a)]). Non-HDL cholesterol was a good predictor for CVD in diabetes according to some population studies, such as the Strong Heart Study [12] and the Hoorn Study [13]. More evidence is needed from intervention trials before drawing definitive conclusions regarding its impact on lipid management. Similarly, whether the determination of postprandial triglyceride levels improves the risk assessment for CHD remains uncertain [14].

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