Tolerance to an oral tryptophan load (50 mg/kg body weight) was evalua
ted in a group of 15 insulin-dependent diabetic patients of both sexes
in poor metabolic control. Tryptophan was measured fluorometrically,
and the plasma levels of the other physiological amino acids were dete
rmined by HPLC. The ratio of the plasma concentration of each large ne
utral amino acid (LNAA) to the sum of the others was calculated to ser
ve as an index for the competitive transport of these amino acids into
the brain. The results show that post-loading plasma tryptophan level
s in diabetic patients increased less than in healthy controls, sugges
ting enhanced liver catabolism of this amino acid (as reported for dia
betic animals). Small changes were observed in the post-loading plasma
concentrations of other amino acids. Therefore, the increment in the
tryptophan/LNAA ratio in controls (basal, 0.12+/-0.01; 120 min after t
he load, 0.89+/-0.04; 240 min, 0.51+/-0.03) was greatly attenuated in
diabetic patients (basal, 0.11+/-0.01, NS; 120 min, 0.46+/-0.04, p < 0
.01; 240 min, 0.31+/-0.04, p < 0.01). Post-loading excursions in some
other ratios were slightly larger in control than diabetic subjects. T
hese differences, which may occur to a lesser extent after a protein-r
ich meal, could modify the availability of precursor amino acids to th
e brain for synthesis of neurotransmitters. Thus, as happens in certai
n animal species, an impairment of the post-absorptive accumulation of
tryptophan and serotonin in the brain may occur in diabetic patients
as a result of altered metabolic disposal of tryptophan.