Pancreatic Polypeptide Responses to Protein Meal Challenges in Obese but Otherwise Normal Children and Obese Children with Prader-Willi Syndrome*

Abstract

Children with hyperphagia and obesity of Prader-Willi syndrome (PWS) have previously been shown to have blunted pancreatic polypeptide (PP) response to low protein meal stimulation. To evaluate the effects of various protein challenges on PP release in children with PWS, we administered both a low protein (0.2 g/kg) and a high protein (2.0 g/kg) meal stimulation test to 12 children previously diagnosed as having PWS and to an age- and weight-matched group of 19 obese but otherwise normal children. Serum samples were collected just before and for 3 h after meal ingestion. The mean (+/- SD) age was 11.7 +/- 4.2 yr for the PWS group and 10.3 +/- 3.8 yr for the obese group (P = 0.323). The percent ideal body weight for height for the PWS group (mean +/- SD 186 +/- 48%) was not significantly different from the percent ideal body weight for height for the obese group (174 +/- 35%; P = 0.421). Peak PP responses were significantly less for the PWS group than for the obese group for both the low and high protein meal stimulations. The mean (+/- SE) peak PP response with the low protein meal was 76.1 +/- 13 pg/ml for the PWS group and 302 +/- 93 pg/ml for the obese group (P less than 0.05). The mean peak response with the high protein meal was 181 +/- 51 pg/ml for the PWS group and 581 +/- 127 pg/ml for the obese group (P less than 0.01). Glucose rises were similar for both tests, although the PWS group did have a slightly smaller rise in glucose after the low protein stimulation than was observed in the obese group. The insulin response was also significantly less for the low protein meal in the PWS group compared to the low protein insulin response of the obese group. There were no significant differences in the insulin responses observed in both groups with the high protein meal test. This study confirms our previous observation and suggests that many children with PWS have a functional deficiency of PP. Our current study demonstrates that this condition is not a result of their obese condition or an alteration in their response threshold to protein.

Ghrelin in obesity and endocrine diseases

“…However such interventions may also lower circulating anorexigenic gastroenteropancreatic hormones which may complicate their interpretation (De et al, 2008;Tan et al, 2004). Thus although other pathological defects are felt to cause or contribute to hyperphagia in PWS, including reduced circulating anorexigenic pancreatic polypeptide levels (Zipf et al, 1983), hypothalamic dysfunction (Goldstone et al, 2003;Goldstone, 2004), defects in brain reward and satiety systems (Hinton et al, 2006;Holsen et al, 2006;Miller et al, 2007), and decreased brain-derived neurotrophic factor (BDNF) which functions downstream of leptin and POMC/MC4R signalling (Han et al, 2010), it will need the clinical development of ghrelin antagonists or GOAT inhibitors to be able to definitively assess the role of hyperghrelinemia in the hyperphagia of PWS.…”

Appetite hormones and the transition to hyperphagia in children with Prader-Willi syndrome

“…Pancreatic polypeptide Previous studies have found that, compared with non-obese and obese controls, fasting levels of PP are either normal 22,23,45 or decreased, 10,21,35 and post-prandial levels decreased, 10,21 --23,35,45 in both children over the age of 5 --7 years and adults with PWS. Although eating behaviour was rarely described in the non-adult studies, most of the children did have marked obesity.…”

Appetite control

“…PP does appear to be an efficacious treatment for hyperphagia secondary to PraderWilli syndrome. These patients have blunted basal and post-prandial PP responses which may contribute to their hyperphagia and obesity (Zipf et al 1981(Zipf et al , 1983. A twice-daily 'replacement' of PP by infusion results in a 12% reduction in food intake during the therapy (Berntson et al 1993).…”