Lipid modulation in insulin-dependent diabetes mellitus: effect on microvascular outcomes.

Although hyperlipidemia is associated with the development of diabetes complications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controlled pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patients without overt nephropathy. Thirty-nine patients with LDL cholesterol 100-160 mg/dl, >10 year duration of diabetes and an albumin excretion rate (AER) <200 microg/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progression of retinopathy status, change in vibratory threshold, and development of new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiation levels by the American Diabetes Association, the trial was terminated early with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 year, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on treatment 105.0 vs. 127.7, P<.001). Simvastatin therapy was associated with a slower rise in AER compared to placebo, though the result was not statistically significant (median rate of change/month 0.004 vs. 0.029). There was a trend towards slower progression of neuropathy as measured by vibratory threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). There was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin may have a beneficial effect on early nephropathy and diabetic neuropathy, justifying a fully powered trial. However, this would be difficult under current treatment guidelines.