In patients with Type 1 diabetes in good glycemic control the lipid profile is very similar to lipid profiles in the general population. In contrast, in patients with Type 2 diabetes, even when in good glycemic control, there are abnormalities in lipid levels. Specifically, patients with Type 2 diabetes often have an increase in serum triglyceride levels, increased VLDL and IDL, decreased HDL, and an increase in small dense LDL, a lipoprotein particle that may be particularly atherogenic. It should be recognized that these lipid changes are characteristic of the metabolic syndrome (insulin resistance syndrome). Since a high percentage of patients with Type 2 diabetes are to some degree insulin resistant and have the metabolic syndrome, it is not surprising that the prevalence of increased triglycerides and small dense LDL and decreased HDL is common in patients with Type 2 diabetes even when these patients are in good glycemic control. In both Type 1 and Type 2 diabetes poor glycemic control increases serum triglyceride levels, VLDL and IDL, and decreases HDL. Poor glycemic control can also result in a modest increase in LDL cholesterol, which because of the elevation in triglycerides is often in the small dense subfraction. It is therefore important to optimize glycemic control in patients with diabetes because this will have secondary beneficial effects on lipid levels. Lp (a) levels are usually within the normal range in patients with Type 2 diabetes and do not appear to be greatly effected by glycemic control. In patients with Type 1 diabetes Lp (a) levels are frequently elevated and improvements in glycemic control result in decreases in Lp (a) levels. The development of microalbuminuria and the onset of renal disease are associated with an increase in Lp (a) levels.

The methods used to improve glycemic control may have an impact on lipid levels above and beyond their effects on glucose metabolism. Specifically, insulin, sulfonylureas, meglinitides, and alpha-glucosidase inhibitors do not consistently alter lipid levels other than by effecting glucose control. In contrast, metformin and thiazolidindiones have effects independent of glycemic control on serum lipid levels. Metformin decreases serum triglyceride levels and may modestly decrease LDL cholesterol without altering HDL cholesterol. The effect of thiazolidindiones appears to depend on which agent is used. Rosiglitazone increases serum LDL cholesterol levels, increases HDL cholesterol levels, and only decreases serum triglycerides if the baseline levels are high. In contrast, pioglitazone has less impact on LDL cholesterol levels, increases HDL cholesterol levels, and decreases serum triglyceride levels. It should be noted that reductions in the small dense LDL subfraction and an increase in the large buoyant LDL subfraction are seen with both thiazolidindiones. In a recent randomized head to head trial it was shown that pioglitazone decreased serum triglyceride levels and increased serum HDL cholesterol levels to a greater degree than rosiglitazone treatment. Additionally, pioglitazone increased LDL cholesterol levels less than rosiglitazone. In contrast to the differences in lipid parameters, both rosiglitazone and pioglitazone decreased HBA1c and c-reactive protein to a similar extent. The mechanism by which pioglitazone induces more favorable changes in lipid levels than rosiglitazone is unclear.