Postprandial insulin and ghrelin responses can be helpful for the assessment of semi-synthetic diets for patients with inborn errors of metabolism such as phenylketonuria

Objectives: Insulin and ghrelin are endocrine mediators of food intake. Insulin is a well-known activator of glucose and amino acid (AA) uptake for peripheral tissues and ghrelin a stimulus for eating behavior. We investigated insulin and ghrelin responses along with metabolic profiles following ingestion of different AA substitutes commonly used in the treatment of phenylketonuria (PKU) to assess endocrine signals of anabolism and metabolic effects.

Methods: 20 healthy and 3 phenylketonuric adults ingested different AA mixtures with or without carbohydrates and fat (Anamix, Easiphen or p-am 3, dose 0.35g AA/kg bw), isocaloric milk powder was tested for control purposes. Insulin and ghrelin were measured together with serum AA and glucose every 30'up to 5 hours.

Results: The insulin peaks, up to 500% compared to baseline, occurred at 30' and were 100% higher after intake of AA plus macronutrients along with normoglycemia. Peak AA concentrations were achieved at approx. 60' postprandially for supplemented AA powders, significantly later than for pure AA mixtures. The phenylalanine / tyrosine ratio declined by 25% in phenylketonuric patients, indicative of improved metabolic control. Ghrelin showed a nadir at 60', followed by a rise leading to a 30% increase of initial concentrations for pure AA, compared to more constant levels following intake of preparations with macronutrients.

Conclusion: An oral AA bolus together with macronutrients is followed by a higher insulin secretion and more stable ghrelin concentrations, normoglycemia and retardation of hyperaminoacidemia, whereas pure AA mixtures exert weaker anabolic effects. Therefore, endocrine profiles following ingestion of dietary preparations can be of value for the assessment of semi-synthetic diets in order to optimize metabolic control in patients with inborn errors of metabolism.