Apolipoprotein E kinetics:: influence of insulin resistance and type 2 diabetes

BACKGROUNDS AND AIMS: Insulin resistance related to obesity and diabetes is characterized by an increase in plasma TG-rich lipoprotein concentrations. Apolipoprotein (apo) E plays a crucial role in the metabolism of these lipoproteins and particularly in the hepatic clearance of their remnants. The aim of this study was to explore apoE kinetics of obese subjects and to determine what parameters could influence its metabolism. METHODS: Using stable-isotope labelling technique ([H-2(3)]-leucine-primed constant infusion) and monocompartmental model (SAAM 11 computer software), we have studied the plasma kinetics of very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) apoE in 12 obese subjects (body mass index (BMI) 27.4-36.6 kg/m(2)): Seven were type 2 diabetics (age 47-65 y; HbA1 c 7.1-10.2%) and five were non-diabetics (age 40-51 y, HbA1c: 4.9-5.3%). Six of the diabetic subjects were insulin resistant as assessed by insulin sensitivity index (HOMA 2.6 -10.0), while non-diabetic subjects were all insulin sensitive (HOMA 1.2-2.1). RESULTS: Plasma VLDL and HDL apoE concentrations were significantly higher in diabetic than in non-diabetic subjects (5.74 +/- 1.60 vs 1.46 +/- 1.74mg/l, P<0.01 and 17.81 +/- 6.67 vs 9.97 +/- 3.32mg/l, P<0.05). These increased levels were associated with significantly higher absolute production rate (APR) of VLDL and HDL apoE (0.714 +/- 0.343 vs 0.130 +/- 0.200mg/kg/day, P<0.01, and 0.197 +/- 0.087 vs 0.080 +/- 0.060mg/kg/day, P<0.05, respectively) while no significant difference was found for fractional catabolic rate (FCR) of VLDL and HDL apoE (3.44 +/- 1.64 vs 1.97+/-0.84/day and 0.30+/-0.12 vs 0.19 +/- 0.09/day, respectively). In the whole population, BMI was not correlated with any of apoE kinetic data. HOMA was positively correlated with FCR of VLDL apoE (r=0.64, P < 0.05) and tended to be correlated with APR of VLDL apoE (r=0.58, P=0.06). HbA1c was positively correlated with APR and FCR of both VLDL apoE (r= 0.91 and 0.78, P < 0.01, respectively) and HDL apoE (r= 0.66 and 0.69, P < 0.05, respectively). CONCLUSION: Obese diabetics are characterized by elevated VLDL and HDL apoE levels associated with enhancement of VLDL and HDL apoE production rates. Whereas obesity did not influence apoE kinetic parameters in itself, insulin resistance may lead to an increase in VLDL apoE production and fractional catabolic rates. Diabetes and the glycemic control may also specifically influence the kinetics of both VLDL and HDL apoE. All together, these disorders should explain at least part of the increase in VLDL and HDL apoE observed in diabetes.