Lm Scheek

Type 2 diabetes mellitus is associated with differential effects on plasma cholesteryl ester transfer protein and phospholipid transfer protein activities and concentrations

Background: Human plasma contains two lipid transfer proteins, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), which are crucial in reverse cholesterol transport. Methods: Plasma CETP and PLTP activity levels and concentrations in 16 type 2 diabetic patients and 16 matched healthy subjects were determined, and these data were correlated to clinical variables, including insulin sensitivity and lipid levels. Results: Plasma triglycerides were higher (p<0.02) and high‐density lipoprotein (HDL) cholesterol (p<0.02) was lower in diabetic patients. Plasma CETP activity and concentrations were not significantly different between diabetic and healthy subjects, but CETP specific activity was lower in diabetic patients (p<0.001). Multiple regression analysis showed that plasma CETP activity was positively related to CETP concentration (p=0.0001) and negatively to the diabetic state (p<0.002) or to HbA1c (p<0.02). PLTP activity (p<0.05) and specific activity were higher (p<0.05), whereas there was no difference in PLTP concentration between the two groups. There was no significant bivariate correlation between PLTP concentration and activity, in either healthy or diabetic subjects. Multiple regression analysis did disclose positive relationships of PLTP activity with PLTP concentration (p=0.0001), plasma triglycerides (p=0.0001) and waist/hip ratio (p=0.0001), but not with the diabetic state or HbA1c. Conclusions: Neither CETP nor PLTP activity was independently associated with insulin sensitivity. Specific CETP activity is decreased in type 2 diabetes mellitus. In contrast, specific PLTP activity is higher in diabetes, as a result of the association of plasma PLTP activity with plasma triglycerides and obesity. Measurement of both plasma lipid transfer protein activity and mass levels may thus provide extra information in diabetes mellitus.

Insulin decreases plasma cholesteryl ester transfer but not cholesterol esterification in healthy subjects as well as in normotriglyceridaemic patients with type 2 diabetes.

Plasma cholesterol esterification (EST) and subsequent cholesteryl ester transfer (CET) from high‐density lipoproteins (HDLs) towards apolipoprotein (apo) B‐containing lipoproteins are key steps in HDL metabolism.

Replacement of dietary saturated fat with trans fat reduces serum paraoxonase activity in healthy men and women

A high intake of saturated fat and of trans isomers of unsaturated fat is associated with increased risk of cardiovascular disease. Recently, we found that replacement of saturated fat by trans fat in a dietary controlled study with 32 men and women decreased serum high-density lipoprotein (HDL)-cholesterol and impaired endothelial function, suggesting that trans fats have stronger adverse effects than saturated fats. To investigate this further, we measured the activity of serum paraoxonase (PON1) in serum samples of the same volunteers after consumption of both diets. PON1 protects lipoproteins from oxidative damage, and higher PON1 activity appears to be related to lower cardiovascular disease risk. PON1 activity (mean +/- SD) was 195.9 +/- 108.9 U/L after 4 weeks of consuming a diet with 22.9% of energy (en%) from saturated fat and 184.5 +/- 99.3 U/L when 9.3 en% from saturated fat was replaced by trans fat (P =.006). Thus, replacement of dietary saturated fat by trans fat not only decreased serum HDL-cholesterol and impaired endothelial function, but also decreased the activity of serum paraoxonase. Whether the changes in serum paraoxonase activity caused the changes in endothelial function needs to be further investigated.