Objective: To identify genetic factors related to individual differences in lipid responses to intensified treatment in Type 2 diabetes.
Design and methods: After evaluation and intensification of their treatment, 107 Type 2 diabetes patients with poor metabolic control were re-evaluated after mean follow-up time of 15.6 (0, 4) (SE) months. The genes coding major lipid regulatory proteins and their relations to plasma lipid and lipoprotein changes were studied.
Results: During the follow-up, levels of glycohemoglobin A1 (GHBA1) decreased (-1.7%), plasma HDL cholesterol (+0.05 mmol/l) and lipoprotein (a) [Lp(a)] (+4.2 mg/dl) increased, while triglyceride (TG) levels decreased (-1.2mmol/l) despite mean weight gain of 2.1 kg (p from <0.01 to <0.001). Of the gene markers studied, the lipoprotein lipase (LPL) Pvull (p=0.005) independently affected changes in HDL-cholesterol and was associated with the frequency of coronary heart disease (CHD). Lp(a) changes were associated with apolipoprotein B (ApoB) Glu4154Lys polymorphism (p=0.004).
Conclusions: These results suggest that genetic variations at LPL and ApoB loci are among the factors contributing to the variability in response to lipid parameters to therapy in Type 2 diabetes. LPL Pvull rare allele homozygote status seems to be beneficial with more favorable lipid changes and protection against CHD.