TY - JOUR
T1 - A broad-based metabolic approach to study VLDL apoB100 metabolism in patients with ESRD and patients treated with peritoneal dialysis
AU - Prinsen, Berthil H. C. M. T.
AU - Rabelink, Ton J.
AU - Romijn, Johannes A.
AU - Bisschop, Peter H.
AU - de Barse, Martina M. J.
AU - de Boer, José
AU - van Haeften, Timon W.
AU - Barrett, P. Hugh R.
AU - Berger, Ruud
AU - de Sain-van der Velden, Monique G. M.
PY - 2004
Y1 - 2004
N2 - BACKGROUND: Dyslipidemia is often observed in patients with end-stage renal disease (ESRD) and is associated with cardiovascular diseases. Peritoneal dialysis treatment may further deteriorate the lipoprotein abnormalities, suggesting that peritoneal dialysis alters lipid metabolism. METHODS: To study the mechanisms involved in these abnormalities in peritoneal dialysis, we measured insulin sensitivity, free fatty acids release, de novo lipogenesis (DNL), very low-density lipoprotein (VLDL) apoB100 kinetics and cholesterol synthesis in vivo in ESRD (N= 6), peritoneal dialysis patients (N= 5), and controls (N= 7) using stable isotopes. RESULTS: Insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, tended to be lower in ESRD and peritoneal dialysis compared to controls [P= 0.08 by analysis of variance (ANOVA)]. Free fatty acid release during the euglycemic hyperinsulinemic clamp tended to be higher in ESRD and peritoneal dialysis compared to controls (P= 0.08 by ANOVA), while DNL and fractional cholesterol synthesis were normal. VLDL-1 apoB100 (P <0.05) and VLDL-2 apoB100 pool sizes (P <0.05) were significantly higher in peritoneal dialysis patients compared to controls. The increased VLDL-1 apoB100 pool size was explained by increased VLDL-1 apoB100 synthesis (P <0.05) in combination with reduced VLDL-1 apoB100 catabolism (P <0.01), while the increased VLDL-2 apoB100 pool was explained by reduced catabolism (P <0.01). CONCLUSION: Both VLDL-1 apoB100 and VLDL-2 apoB100 pool sizes are increased in peritoneal dialysis patients, due to disturbances both in synthesis and catabolism. VLDL-1 apoB100 production is, at least partially, explained by increased free fatty acid availability secondary to peripheral insulin resistance, thus identifying insulin resistance as potential therapeutic target in peritoneal dialysis patients
AB - BACKGROUND: Dyslipidemia is often observed in patients with end-stage renal disease (ESRD) and is associated with cardiovascular diseases. Peritoneal dialysis treatment may further deteriorate the lipoprotein abnormalities, suggesting that peritoneal dialysis alters lipid metabolism. METHODS: To study the mechanisms involved in these abnormalities in peritoneal dialysis, we measured insulin sensitivity, free fatty acids release, de novo lipogenesis (DNL), very low-density lipoprotein (VLDL) apoB100 kinetics and cholesterol synthesis in vivo in ESRD (N= 6), peritoneal dialysis patients (N= 5), and controls (N= 7) using stable isotopes. RESULTS: Insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, tended to be lower in ESRD and peritoneal dialysis compared to controls [P= 0.08 by analysis of variance (ANOVA)]. Free fatty acid release during the euglycemic hyperinsulinemic clamp tended to be higher in ESRD and peritoneal dialysis compared to controls (P= 0.08 by ANOVA), while DNL and fractional cholesterol synthesis were normal. VLDL-1 apoB100 (P <0.05) and VLDL-2 apoB100 pool sizes (P <0.05) were significantly higher in peritoneal dialysis patients compared to controls. The increased VLDL-1 apoB100 pool size was explained by increased VLDL-1 apoB100 synthesis (P <0.05) in combination with reduced VLDL-1 apoB100 catabolism (P <0.01), while the increased VLDL-2 apoB100 pool was explained by reduced catabolism (P <0.01). CONCLUSION: Both VLDL-1 apoB100 and VLDL-2 apoB100 pool sizes are increased in peritoneal dialysis patients, due to disturbances both in synthesis and catabolism. VLDL-1 apoB100 production is, at least partially, explained by increased free fatty acid availability secondary to peripheral insulin resistance, thus identifying insulin resistance as potential therapeutic target in peritoneal dialysis patients
U2 - https://doi.org/10.1111/j.1523-1755.2004.00466.x
DO - https://doi.org/10.1111/j.1523-1755.2004.00466.x
M3 - Article
C2 - 14871427
SN - 0085-2538
VL - 65
SP - 1064
EP - 1075
JO - Kidney International
JF - Kidney International
IS - 3
ER -