Miller Jennifer L, Linville Tiffany D, Dykens Elisabeth M
J Pediatr Endocrinol Metab. 2014 Jan;27(1-2):23-9. doi: 10.1515/jpem-2013-0116.
Prader-Willi syndrome (PWS) is one of the most commonly recognized causes of early-onset childhood obesity. Individuals with PWS have significant hyperphagia and decreased recognition of satiety. The exact etiology of the hyperphagia remains unknown and, therefore, untreatable. We conducted a pilot, open-label study of response to metformin in 21 children with PWS and six with early morbid obesity (EMO). Participants had significant insulin resistance and glucose intolerance on oral glucose tolerance testing (OGTT) and were started on metformin for these biochemical findings. We administered the Hyperphagia Questionnaire to parents of patients before and after starting metformin treatment. Both the PWS and EMO groups showed significant improvements in food-related distress, anxiety, and ability to be redirected away from food on the Hyperphagia Questionnaire. In the PWS group, improvements were predominantly seen in females. Within the PWS group, responders to metformin had higher 2-h glucose levels on OGTT (7.48 mmol/L vs. 4.235 mmol/L; p=0.003) and higher fasting insulin levels (116 pmol/L vs. 53.5 pmol/L; p=0.04). Additionally, parents of 5/13 individuals with PWS and 5/6 with EMO reported that their child was able to feel full while on metformin (for many this was the first time they had ever described a feeling of fullness). Metformin may improve sense of satiety and decrease anxiety about food in some individuals with PWS and EMO. Positive response to metformin may depend on the degree of hyperinsulinism and glucose intolerance. Nonetheless, the results of this pilot study bear further investigation.
普拉德-威利综合征（PWS）是儿童期早发肥胖最常见的病因之一。患有PWS的个体存在明显的食欲亢进，且饱腹感识别能力下降。食欲亢进的确切病因尚不清楚，因此无法治疗。我们对21名患有PWS的儿童和6名患有早期严重肥胖（EMO）的儿童进行了一项关于二甲双胍反应的开放性试验研究。参与者在口服葡萄糖耐量试验（OGTT）中存在明显的胰岛素抵抗和葡萄糖不耐受，并因这些生化结果开始服用二甲双胍。我们在开始二甲双胍治疗前后，向患者父母发放了食欲亢进问卷。PWS组和EMO组在食欲亢进问卷中与食物相关的困扰、焦虑以及被转移对食物注意力的能力方面均有显著改善。在PWS组中，主要在女性身上看到了改善。在PWS组内，对二甲双胍有反应者在OGTT中的2小时血糖水平较高（7.48 mmol/L对4.235 mmol/L；p = 0.003），空腹胰岛素水平也较高（116 pmol/L对53.5 pmol/L；p = 0.04）。此外，13名PWS患者中的5名和6名EMO患者中的5名的父母报告说，他们的孩子在服用二甲双胍期间能够有饱腹感（对许多人来说，这是他们第一次描述有饱腹感）。二甲双胍可能会改善某些患有PWS和EMO的个体的饱腹感，并减少对食物的焦虑。对二甲双胍的阳性反应可能取决于高胰岛素血症和葡萄糖不耐受的程度。尽管如此，这项初步研究的结果值得进一步研究。
