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 i nvestigated whether 13-cis-retinoic acid treatment decreases insulin sensit ivity. Methods We studied 11 men [aged 24 +/-2 years (mean +/- SEM), body mass ind ex (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 af ter the end of treatment using the euglycaemic hyperinsulinaemic clamp tech nique. 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 value s returned to baseline. 13-cis-Retinoic acid treatment also resulted in inc reased very low density lipoprotein (VLDL) and low density lipoprotein (LDL ) cholesterol, increased VLDL triglyceride, and increased VLDL and LDL phos pholipid concentrations. Conclusion Treatment of acne with 13-cis-retinoic acid reduces insulin sens itivity and induces alterations in lipid metabolism resembling those of the insulin resistance syndrome. Copyright (C) 2001 John Wiley & Sons, Ltd.