B. Dyslipidemia g
associated with the insulin resistance syndrome. Thus, this dyslipidemic pattern
(by its association with insulin resistance) may be observed in the prediabetic state and may precede the diagnosis of type 2 diabetes. LDL cholesterol levels in insulin-resistant patients and those with type 2 diabetes may be comparable to those seen in the general population. However, LDL compositional differences may make these particles more atherogenic (89,91). Specifically, hyperinsuli-nemia appears to be significantly associated with both quantitative changes (e.g., increased triglycerides, high Apo B, low Apo A1 levels) in the lipoproteins and also qualitative changes (e.g., low LDL cholesterol/Apo B and low HDL cholesterol/low Apo A1) (88-92). It is further established that insulin levels appear not to be associated with the absolute concentration of the LDL cholesterol, but are associated with the relative decrease in the small dense LDL particles termed LDL subclass pattern B. Insulin resistance has also been associated with this preponderance of small dense LDL particles (86,87). It is the small dense LDL particle that has been suggested to be the more atherogenic LDL. The association of lipoprotein abnormalities to insulin resistance has generated investigation as to whether improvement in insulin sensitivity with pharmacological agents can improve the dyslipidemia. Studies have suggested that insulin sensitizers (e.g., thiazolidinediones) may favorably improve LDL size. Although it has been shown that the ratio of LDL to HDL cholesterol may not change with treatment with insulin sensitizers, the qualitative properties of LDL may change with their use: large (buoyant) LDL is increased and small dense LDL is decreased (93). Whether the compositional change in LDL is indeed secondary to improvement in insulin resistance or secondary to other characteristics of insulin sensitizers (e.g., antioxidant effect) is an area of great debate because there appears to be no relationship between the effect of glitazones on lipoproteins and on insulin sensitivity.
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