Lipid modulation in insulin-dependent diabetes mellitus - Effect on microvascular outcomes

Although hyperlipidemia is associated with the development of diabetes comp lications, the effect of lipid reduction on microvascular complications is unknown. We initiated a 2-year, randomized, double-blinded placebo-controll ed pilot trial of simvastatin/diet vs. diet alone in Type 1 diabetic patien ts without overt nephropathy. Thirty-nine patients with LDL cholesterol 100 -160 mg/dl, > 10 year duration of diabetes and an albumin excretion rate(AE R) < 200 mug/min were recruited for study. The primary end-point was change in AER. Secondary end-points were change in ankle-brachial index, progress ion of retinopathy status, change in vibratory threshold, and development o f new clinical neuropathy. Nineteen patients were treated with simvastatin and twenty with placebo. However, because of the lowering of drug initiatio n levels by the American Diabetes Association, the trial was terminated ear ly with 2 subjects reaching 2 years, 17 reaching 18 months, 36 reaching 1 y ear, and all 6 months. Simvastatin significantly reduced total cholesterol (mean on treatment 173.4 vs. 191.4, P=.020) and LDL cholesterol (mean on tr eatment 105.0 vs. 127.7, P < .001). Simvastatin therapy was associated with a slower rise in AE:R compared to placebo, though the result was not stati stically significant (median rate of change/month 0.004 vs. 0.029). There w as a trend towards slower progression of neuropathy as measured by vibrator y threshold (median change at 1 year 0.03 simvastatin vs. 0.94, P=.07). The re was no difference in change in ankle-brachial index, clinical neuropathy status, or retinopathy status. In conclusion, treatment with simvastatin m ay have a beneficial effect on early nephropathy and diabetic neuropathy, j ustifying a fully powered trial. However, this would be difficult under cur rent treatment guidelines. (C) 2001 Elsevier Science Inc. All rights reserv ed.