Effect of pravastatin on low-density lipoprotein oxidation and myocardial perfusion in young adults with type 1 diabetes.
OBJECTIVE
Diabetes has been associated with increased oxidative stress and impaired vascular function. Statins have been shown to reduce low-density lipoprotein (LDL) oxidizability and improve myocardial perfusion in hypercholesterolemic nondiabetic subjects. We studied whether pravastatin decreases LDL oxidation and improves myocardial perfusion in normocholesterolemic subjects with type 1 diabetes.


RESULTS
In this randomized, double-blind study, myocardial perfusion was measured at rest and during dipyridamole stimulation with positron emission tomography and [15O]H2O during hyperinsulinemic euglycemia in 42 patients (age 30+/-6 years; LDL cholesterol 2.48+/-0.57 mmol/L) before and after 4-month treatment with pravastatin 40 mg/d or placebo. In addition, 12 healthy nondiabetic subjects were studied. LDL oxidation was measured by determining the level of baseline diene conjugation in lipids extracted from LDL. The level of LDL oxidation was similar in the pravastatin and placebo groups before treatment (23.9+/-4.6 versus 25.6+/-9.5 micromol/L, respectively) and decreased significantly during pravastatin treatment to 19.5+/-5.0 micromol/L (P<0.005). Myocardial perfusion reserve was significantly lower in diabetic patients compared with controls (4.15+/-1.29 versus 5.31+/-1.86, P<0.05) and did not change after treatment. Glycemic control and insulin sensitivity remained unchanged during treatment.


CONCLUSIONS
Pravastatin treatment, resulting in decreased LDL oxidation, did not improve myocardial perfusion reserve in subjects with type 1 diabetes.
Janatuinen
Tuula
T
Turku PET Centre, Turku University Central Hospital, PO Box 52, FIN-20521 Turku, Finland. tuula.janatuinen@pet.tyks.fi
Knuuti
Juhani
J
Toikka
Jyri O
JO
Ahotupa
Markku
M
Nuutila
Pirjo
P
Rönnemaa
Tapani
T
Raitakari
Olli T
OT
D000328:Adult; D003326:Coronary Circulation / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003925:Diabetic Angiopathies / Q000473:pathology; D004176:Dipyridamole / Q000494:pharmacology; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006321:Heart / Q000000981:diagnostic imaging*; D006439:Hemodynamics; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D010084:Oxidation-Reduction; D049268:Positron-Emission Tomography; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D012171:Retinal Vessels / Q000473:pathology
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D004176:Dipyridamole; D017035:Pravastatin