Hyperglycemia does not explain the loss of function of apolipoproteinC1 on CETP activity in people with type 1 diabetes

Abstract Background HDL-associated apolipoproteinC1 (apoC1) has been demonstrated to be the main physiological cholesterol ester transfer protein (CETP) inhibitor. CETP promotes cholesterol ester and triglyceride exchanges between HDL and apolipoprotein-B containing lipoproteins, and augmented CETP activity has been shown to be associated with macrovascular complications in patients with type 1 diabetes (T1D). In a previous study, apoC1 lost its ability to inhibit CETP in patients with T1D and in vitro glycation of apoC1 impaired its ability to inhibit CETP. Thus, we hypothesize that hyperglycemia could be a factor implicated in the loss of the inhibitory effect of apoC1 on CETP in people with T1D. We performed a prospective study in patients with uncontrolled T1D aiming to determine whether significant improvement of glycemic control could restore the inhibitory effect of apoC1 on CETP. Methods We studied 98 patients with uncontrolled T1D (HbA1c>9%) and no treatment that could influence lipoproteins metabolism at baseline, and 3 months after improvement of glycemic control by optimization of T1D therapy, and 92 normoglycemic normolipidemic control subjects. CETP activity was assessed by a radioactive method and plasma apoC1 levels were measured by ELISA in every participant. In addition, the different isoforms of apoC1 were determined by mass spectrometry in 20 patients with T1D and in 20 controls. Results After 3 months of treatment intensification, mean HbA1c was significantly reduced in patients with T1D (8.7±1.7 vs. 10.8±2, p<0.0001). CETP activity was not significantly modified after improvement of glycemic control. A significant negative association between plasma apoC1 and CETP activity was observed in controls (r=-0.0006, p= 0.013) but not in uncontrolled patients with T1D, at baseline and at 3 months. We did not find any glycated form of apoC1 using mass spectrometry in people with T1D (at baseline and at 3 months) compared with controls. Conclusion Hyperglycemia, in vivo, does not seem to be a major factor implicated in the loss of apoC1 ability to inhibit CETP activity observed in T1D. Other factors, such as qualitative abnormalities of lipoproteins, could be involved. Further studies are needed to better understand apoC1 dysfunction in T1D.