Urine samples from patients with newly diagnosed juvenile diabetes and predibetic coma or ketonuria, but no acid-base disturbances in the blood, have been analyzed for dicarboxylic acids by combined gas-liquid chromatography and mass spectrometry.
The precomatose patients excreted up to 210 and 38 μg./1 mg. of creatinine, respectively, of n-hexanedioic and n-octanedioic acid. The excretion was almost normalized within a few hours by insulin treatment. Nonacidotic patients with ketonuria excreted 9.2 ± 5.1 mg./24 hr. of n-hexanedioic acid, and some also excreted slightly increased amounts of n-octanedioic acid. All patients excreted normal amounts of 3-methylhexanedioic acid, which was unaffected by insulin treatment.
Our findings direct attention to a metabolic pathway which may be of importance in the pathogenesis of ketosis in diabetes mellitus, namely the formation of short-chain dicarboxylic acids (for instance, intermediates of the tricarboxylic acid cycle) by ω-oxidation of fatty acids followed by β-oxidations of the dicarboxylic acids thus formed.