Ameliorating Hypertension and Insulin Resistance in Subjects at Increased Cardiovascular Risk. Effects of Acetyl-L-Carnitine Therapy

Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-l-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-l-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR ≤7.9 (n=16) or >7.9 (n=16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (n=32; P =0.001; r =−0.545), and patients with GDR ≤7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-l-carnitine increased GDR from 4.89±1.47 to 6.72±3.12 mg/kg per minute ( P =0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR ≤7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups ( P =0.017, ANCOVA). Systolic blood pressure decreased from 144.0±13.6 to 135.1±8.4 mm Hg and from 130.8±12.4 to 123.8±10.8 mm Hg in the lower and higher GDR groups, respectively ( P P