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

• Published in: Diabetic medicine Vol. 22; no. 12; pp. 1647 - 1656
• Main Authors: Paniagua, J. A., López-Miranda, J., Pérez-Martínez, P., Marín, C., Vida, J. M., Fuentes, F., Fernández de la Puebla, R. A., Pérez-Jiménez, F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2005; Blackwell
• Subjects: Adult; Aged; Albuminuria - drug therapy; Albuminuria - metabolism; Biological and medical sciences; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Double-Blind Method; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; endothelium; Endothelium, Vascular - drug effects; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Lipoproteins, LDL - blood; Lipoproteins, LDL - drug effects; Male; Medical sciences; microalbuminuria; Middle Aged; Nephrology. Urinary tract diseases; oxidative stress; Pyridines - therapeutic use; statin; Type 2 diabetes; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; Vasodilation - drug effects; Endocrinopathy; Short term; Type 2 diabetes; Oxidative stress; Endothelial cell; Urinary system disease; Albumin; Metabolic diseases; Early stage; Statin derivative; Glucose; Endothelium; Lipoprotein LDL; statin; Serum; Oxidation; Microalbuminuria; Proteinuria
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/j.1464-5491.2005.01703.x

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.