Hormonal and metabolic effects of carbohydrate restriction in children with Prader Willi syndrome

Abstract

Objective

Macronutrient regulation of hyperphagia and adiposity in PWS is poorly understood. We compared fasting and postprandial concentrations of hormones and metabolites in 8 PWS children (age 9‐18 yr) fed, in random order, low carbohydrate, high fat (LC, 15%carb; 65%fat; 20% protein) and low fat, high carbohydrate (LF, 65%carb, 15%fat, 20% protein) diets matched for calories and protein.

Methods

Participants were randomized to consume either the LC or LF diet during a first hospital admission and the second diet during a subsequent admission. Blood samples were obtained after overnight fasting and 1 hour after a mixed meal.

Results

Relative to subjects consuming the LF diet, subjects consuming the LC diet had: lower post‐prandial insulin concentrations (p=0.02); higher fasting and post‐prandial GLP‐1 concentrations (p<0.02); reduced ratio of fasting ghrelin to GLP‐1 (p=0.0078); increased FFA and fatty acid oxidation, as assessed by concentrations of even‐chain acylcarnitines (p<0.001); lower fasting TG and TG/HDL ratio (p<0.01); and higher concentrations of branch chain amino acids (p<0.01). There were no changes in glucose, GIP, PYY, or adiponectin. CRP, AST, and ALT were all higher (p<0.01) on the LC diet.

Conclusions

Increases in GLP‐1 with low carbohydrate feeding and reductions in the ratio of ghrelin to GLP‐1 might limit food intake and improve glycemic control in PWS. Other potential benefits of carbohydrate restriction may include fat mobilization and oxidation and reductions in the TG/HDL ratio, a marker of insulin resistance. However increases in CRP, AST, and ALT necessitate longer‐term studies of low carbohydrate efficacy and safety.

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