Removal from the plasma of the free and esterified forms of cholesterol and transfer of lipids to HDL in type 2 diabetes mellitus patients

Abstract

Background: The aim was to investigate new markers for type 2 diabetes (T2DM) dyslipidemia related with LDL and HDL metabolism. Removal from plasma of free and esterified cholesterol transported in LDL and the transfer of lipids to HDL are important aspects of the lipoprotein intravascular metabolism. The plasma kinetics (fractional clearance rate, FCR) and transfers of lipids to HDL were explored in T2DM patients and controls, using as tool a nanoemulsion that mimics LDL lipid structure (LDE).

Results: 14C- cholesteryl ester FCR of the nanoemulsion was greater in T2DM than in controls (0.07 ± 0.02 vs. 0.05 ± 0.01 h-1, p = 0.02) indicating that LDE was removed faster, but FCR 3 H- cholesterol was equal in both groups. Esterification rates of LDE free-cholesterol were equal. Cholesteryl ester and triglyceride transfer from LDE to HDL was greater in T2DM (4.2 ± 0.8 vs. 3.5 ± 0.7%, p = 0.03 and 6.8 ± 1.6% vs. 5.0 ± 1.1, p = 0.03, respectively). Phospholipid and free cholesterol transfers were not different.

Conclusions: The kinetics of free and esterified cholesterol tended to be independent in T2DM patients and the lipid transfers to HDL were also disturbed. These novel findings may be related with pathophysiological mechanisms of diabetic macrovascular disease.

Figure 1

Plasma decay curve of¹⁴ C-cholesteryl ester (A) and³ H-cholesterol (B) obtained from type 2 diabetes mellitus (black square) and control (white square) groups. The doubly labeled nanoemulsion was intravenously injected in a bolus, and blood samples were drawn in pre-established intervals over 24 h for measurement of the radioactivity in a scintillation solution. Data are expressed as mean ± SD

Figure 2

Compartmental model used for analysing LDE¹⁴ C- cholesteryl ester (¹⁴ C-CE) and³ H-cholesterol curves (³ H-FC). The model consists of four discrete compartments: two for ¹⁴ C-CE and two for ³ H-FC labels. All compartments are in the intravascular space (1_CE, 2_CE, 1_FC and 2 _FC). LDE, a non-protein lipoprotein nanoemulsion labeled with ¹⁴ C-CE and ³ H-FC were injected intravenously in a bolus (arrow with asterisk) into compartment 1_CE and 1_FC, respectively. A fraction k_1,0CE and k_{1,0 FC} of the labeled lipids is removed to the extravascular space. Competitively, fraction k_1,2CE and k_1,2FC of the injected lipids are converted into compartments 2_CE and 2_FC due to the incorporation of apolipoproteins available in the plasma. Subsequently, the material of those compartments are transferred to the extravascular space following the k_2,0CE and k_2,0FC routes. The samplings, represented by triangles correspond to the indiscriminate combination of compartments 1 and 2.