Blunted Suppression of Acyl-Ghrelin in Response to Fructose Ingestion in Obese Adolescents: The Role of Insulin Resistance

ObjectiveFructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. MethodsAdolescents were divided into lean (n=14), obese insulin sensitive (n=12) (OIS), and obese insulin resistant (n=15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. ResultsBaseline acyl-ghrelin was highest in lean and lowest in OIR (P=0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P=0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P=0.008, lean vs. OIR, P<0.001). OIS became significantly hungrier after fructose (P=0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. ConclusionsCompared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating.