Kweh Frederick A, Sulsona Carlos R, Miller Jennifer L, Driscoll Daniel J
Department of Pediatrics University of Florida College of Medicine Gainesville Florida USA.
Process and Analytical Development Resilience Biotechnologies, Inc. Alachua Florida USA.
Obes Sci Pract. 2023 Feb 17;9(4):383-394. doi: 10.1002/osp4.663. eCollection 2023 Aug.
Prader-Willi syndrome (PWS) is the most frequently diagnosed genetic cause of early childhood obesity. Individuals with PWS typically progress through 7 different nutritional phases during their lifetime. The main objective of this study was to assess potential factors, particularly insulin, that may be responsible for the weight gains in sub-phase 2a and their role in the subsequent increase in fat mass and obesity in sub-phase 2b and insatiable appetite in phase 3.
Fasting plasma insulin levels were measured in children with PWS between the ages of 0-12 years and in age-matched non-PWS participants with early-onset major (clinically severe) obesity (EMO) and in healthy-weight sibling controls (SC).
Participants with PWS in nutritional phases 1a and 1b had plasma insulin levels comparable to SC. However, the transition from phase 1b up to phase 3 in the PWS group was accompanied by significant increases in insulin, coinciding in weight gains, obesity, and hyperphagia. Only individuals with PWS in phase 3 had comparable insulin levels to the EMO group who were higher than the SC group at any age.
Elevated insulin signaling is a probable trigger for weight gain and onset of hyperphagia in children with Prader-Willi syndrome. Regulating insulin levels early in childhood before the onset of the early weight gain may be key in modulating the onset and severity of obesity and hyperphagia in individuals with PWS, as well as in other young children with non-PWS early-onset obesity. Preventing or reversing elevated insulin levels in PWS with pharmacological agents and/or through diet restrictions such as a combined low carbohydrate, low glycemic-load diet may be a viable therapeutic strategy in combating obesity in children with PWS and others with early childhood obesity.
普拉德-威利综合征（PWS）是幼儿期肥胖最常被诊断出的遗传病因。患有PWS的个体在其一生中通常会经历7个不同的营养阶段。本研究的主要目的是评估可能导致2a期体重增加的潜在因素，特别是胰岛素，以及它们在随后的2b期脂肪量增加和肥胖以及3期食欲亢进中所起的作用。
测量了0至12岁患有PWS的儿童、年龄匹配的早发性重度（临床严重）肥胖（EMO）的非PWS参与者以及健康体重的同胞对照（SC）的空腹血浆胰岛素水平。
处于营养1a期和1b期的PWS参与者的血浆胰岛素水平与SC相当。然而，PWS组从1b期到3期的转变伴随着胰岛素的显著增加，这与体重增加、肥胖和食欲亢进同时出现。只有3期的PWS个体的胰岛素水平与EMO组相当，而EMO组在任何年龄都高于SC组。
胰岛素信号升高可能是普拉德-威利综合征患儿体重增加和食欲亢进发作的触发因素。在儿童早期体重增加开始之前尽早调节胰岛素水平，可能是调节PWS个体以及其他非PWS早发性肥胖幼儿肥胖和食欲亢进发作及严重程度的关键。使用药物和/或通过饮食限制，如联合低碳水化合物、低血糖负荷饮食来预防或逆转PWS中升高的胰岛素水平，可能是对抗PWS患儿和其他幼儿期肥胖儿童肥胖的一种可行治疗策略。
