RESUMO
AIM: Metreleptin treatment in lipodystrophy patients improves eating behavior with increased satiety and reduced hunger. However, no data are available whether effects are maintained beyond 52â¯weeks of treatment. METHODS: A prospective study with measurements at baseline and at >150â¯weeks of metreleptin treatment was performed. Five female lipodystrophy patients with indication for metreleptin were included. Behavioral aspects of hunger- and satiety regulation were assessed by validated eating behavior questionnaires and visual analog scales assessing hunger and satiety feelings before and after a standardized meal. RESULTS: Hunger rated on visual analog scales at 120â¯min after the meal significantly decreased from 46⯱â¯10â¯mm at baseline to 17⯱â¯6â¯mm at long-term assessment. Furthermore, satiety at 5 and 120â¯min after the meal significantly increased from baseline to long-term assessment (5â¯min: 70⯱â¯7â¯mm to 87⯱â¯3â¯mm; 120â¯min: 43⯱â¯10â¯mm to 79⯱â¯8â¯mm). On the Three Factor Eating Questionnaire, the mean value of factor 3 (hunger) significantly decreased from 9.2⯱â¯0.2 at baseline to 2.6⯱â¯1.5 at long-term assessment. In the Inventory of Eating Behavior and Weight Problems Questionnaire, mean values for scale 2 (strength and triggering of desire to eat) and scale 7 (cognitive restraint of eating) significantly decreased from baseline (31.6⯱â¯4.8 and 11.4⯱â¯2.2, respectively) to long-term assessment (14.0⯱â¯2.1 and 10.0⯱â¯1.9). CONCLUSION: First evidence is presented that long-term metreleptin treatment of >150â¯weeks has sustained effects on eating behavior with increased satiety, as well as reduced hunger and hunger-related measures.
Assuntos
Comportamento Alimentar/efeitos dos fármacos , Transtornos da Alimentação e da Ingestão de Alimentos/tratamento farmacológico , Fome/efeitos dos fármacos , Leptina/análogos & derivados , Lipodistrofia/tratamento farmacológico , Inquéritos e Questionários , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/metabolismo , Transtornos da Alimentação e da Ingestão de Alimentos/patologia , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Feminino , Humanos , Leptina/administração & dosagem , Lipodistrofia/metabolismo , Lipodistrofia/patologia , Lipodistrofia/fisiopatologia , Pessoa de Meia-IdadeRESUMO
Lipodystrophy (LD) is a rare disease with a paucity of subcutaneous adipocytes and leptin deficiency. Patients often develop severe diabetes and, additionally, show a disturbed eating behavior with reduced satiety. The disturbed eating behavior can be restored by substitution with the leptin analog metreleptin. Long-term effects of metreleptin on resting state brain connectivity in treatment-naive patients with LD have not been assessed. In this study, resting state functional MRI scans and extensive behavioral testing assessing changes in hunger/satiety regulation were performed during the first 52 weeks of metreleptin treatment in nine patients with LD. Resting state connectivity significantly increased over the course of metreleptin treatment in three brain areas (i.e., hypothalamus, insula/superior temporal gyrus, medial prefrontal cortex). Behavioral tests demonstrated that perceived hunger, importance of eating, eating frequencies, and liking ratings of food pictures significantly decreased during metreleptin therapy. Taken together, leptin substitution was accompanied by long-term changes of hedonic and homeostatic central nervous networks regulating eating behavior as well as decreased hunger feelings and diminished incentive value of food. Future studies need to assess whether metreleptin treatment in LD restores physiological processes important for the development of satiety.