Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria
Article first published online: 29 JUN 2005
Volume 22, Issue 12, pages 1647–1656, December 2005
How to Cite
Paniagua, J. A., López-Miranda, J., Pérez-Martínez, P., Marín, C., Vida, J. M., Fuentes, F., Fernández de la Puebla, R. A. and Pérez-Jiménez, F. (2005), Oxidized-LDL levels are changed during short-term serum glucose variations and lowered with statin treatment in early Type 2 diabetes: a study of endothelial function and microalbuminuria. Diabetic Medicine, 22: 1647–1656. doi: 10.1111/j.1464-5491.2005.01703.x
- Issue published online: 29 JUN 2005
- Article first published online: 29 JUN 2005
- Accepted 11 February 2005
- oxidative stress;
- Type 2 diabetes
Aims To investigate the role of HMG-CoA reductase inhibitor (statin) treatment during serum glucose variations on plasma oxidized LDL (ox-LDL) levels in obese patients with early Type 2 diabetes mellitus (T2D) and its relationship to endothelial biomarkers.
Methods In a double-blind, randomized crossover study, 15 obese diet-treated T2D patients received cerivastatin (0.4 mg/day) or placebo for 3 months. Circulating ox-LDL levels were measured fasting and during a euglycaemic–hyperinsulinaemic clamp (∼5.5 mmol/l; EHC) and a hyperglycemic clamp (∼20 mmol/l; HC). An endothelium-dependent flow-mediated dilation (FMD) study was carried out and urinary albumin excretion (UAE) was measured at rest and during EHC. S-ICAM, s-VCAM and basal prothrombotic factors were also measured.
Results During cerivastatin treatment, basal circulating ox-LDL levels decreased by 48% (P < 0.001) compared with placebo. Serum ox-LDL levels decreased during EHC and remained unchanged during HC compared with the fasting state; with cerivastatin treatment these levels were lower compared with placebo both in the fasting state and during the clamp studies. FMD was higher with cerivastatin than with placebo (P < 0.001) and the increments in FMD correlated with decrements in serum ox-LDL levels (r = 0.78, P = 0.001). Microalbuminuria increased during EHC but this was blunted during cerivastatin therapy compared with placebo (P < 0.05). Basal sICAM-1 and sVCAM-1 levels decreased (P < 0.01 and P < 0.05, respectively).
Conclusions In early obese Type 2 diabetic patients, serum ox-LDL levels are influenced by short-term serum glucose variations and lowered with cerivastatin therapy. During cerivastatin treatment, improved flow-mediated endothelium-dependent dilation was associated with decrements in circulating ox-LDL levels and the hyperinsulinaemia-induced urinary albumin excretion was blunted.