Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines

Objective: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. Design: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 μg of acitretin. Methods: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. Results: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364±0.034 versus 0.329±0.051; P <0.05) and HOMA-IR index (1.53±0.73 versus 2.59±1.41; P <0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2±11.7 versus 39.4±10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4±4.4 versus 6.2±2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor α (TNFα) levels, which persisted elevated throughout the treatment. Conclusions: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFα levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.