Dyslipidemia and a reversible decrease in insulin sensitivity induced by therapy with 13-cis-retinoic acid

Background 13-cis-Retinoic acid (Roaccutan(R)) treatment is associated with disturbances in lipid and sometimes also in glucose metabolism. Thus, we investigated whether 13-cis-retinoic acid treatment decreases insulin sensitivity. Methods We studied 11 men [aged 24 +/-2 years (mean +/- SEM), body mass index (BMI) 22.1 +/-0.9 kg/m(2)] who received Roaccutan(R) treatment for acne for a period averaging 5 months but who were otherwise healthy. The insulin. sensitivity of the subjects was measured before, during and 1-3 months after the end of treatment using the euglycaemic hyperinsulinaemic clamp technique. Results Treatment with 13-cis-retinoic acid reduced total (59 +/-4 vs 55 +/-4 mu mol/kg/min, p<0.02), oxidative (25<plus/minus>1 vs 22 +/-2 mu mol/kg/min, p<0.05) and non-oxidative (36<plus/minus>3 vs 33 +/-3 mu mol/kg/min, p=0.05) glucose disposal rate, and there was a 4% increase in HbA(1c) (from 5.2 +/-0.07 to 5.4 +/-0.07%, p<0.02). After treatment cessation these values returned to baseline. 13-cis-Retinoic acid treatment also resulted in increased very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, increased VLDL triglyceride, and increased VLDL and LDL phospholipid concentrations. Conclusion Treatment of acne with 13-cis-retinoic acid reduces insulin sensitivity and induces alterations in lipid metabolism resembling those of the insulin resistance syndrome. Copyright (C) 2001 John Wiley & Sons, Ltd.