We aimed to address the issue whether statins affect insulin resistance. To this end, we combined the available state-of-the art technology for detailed assessment of both whole-body and tissue specific insulin sensitivity in vivo in humans (euglycemic-hyperinsulinemic clamp, stable isotope [6,6-2H2]glucose dilution technique, proton nuclear magnetic resonance spectroscopy - 1H MRS - of liver and skeletal muscle). Outcome measures were determined before and after 8 weeks therapy with 80 mg Simvastatin in hypercholesterolemic patients with type 2 diabetes.

Inclusion Criteria:

• Type 2 diabetic patients with known duration of disease: 3-10 years
• Age: 35-75 years
• BMI<32 kg/m2
• Hypercholesterolemia: fasting serum low density lipoprotein (LDL)
• Cholesterol concentration < 4.16 mmol/L (<160 mg/dl)
• Normotriglyceridemia: fasting plasma triglyceride concentration < 2.75 mmol/L (250 mg/dl)
• Creatinine levels < 1.8 mg /dl
• Liver transaminases < 20% over the upper limit with no active liver disease and CK < 50% above the upper limit
• Blood pressure less than 160/100 mmHg were accepted as eligible for enrollment

Exclusion Criteria:

• Hypertension, cardiovascular disease or metabolic diseases other than T2DM as determined by medical history, physical examination and routine laboratory tests
• Alcohol consumption (more than 10 drinks/week)
• Poor glycemic control (HbA1c<9%)
• Patients requiring insulin, patients with type 1 diabetes
• Patients taking any medicine known to interfere with metabolism of statins or with insulin sensitivity as summarized in an exclusionary drug table
• Patients receiving any hypolipidemic medication or diet during the last 2 months before enrollment