Patients with very long chain acyl-coenzyme A (CoA) dehydrogenase (VLCAD) deficiency—one type of long chain fatty acid oxidation disorder (LCFAOD)—have low fasting concentrations of glucagon which cannot be explained by altered stimuli in plasma, according to a new study published in the journal Metabolites

Previous research has shown that impaired fatty acid oxidation, as in the case of LCFAOD, impairs the secretion of glucagon, an important hormone that mobilizes glucose. However, whether LCFAOD affects levels of glucagon is not known.

In the present study, a team of researchers led by Peter Bergsten, MD, PhD, from the department of medical cell biology at Uppsala University, Sweden, conducted a cross-sectional study in 23 patients. 

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Of these 23 patients, 10 had VLCAD deficiency, 7 had medium chain fatty acid oxidation disorder, and 6 had carnitine uptake deficiency. The patients were similar in age, sex, weight, and height.

Read more about the causes of the different types of LCFAOD

The researchers measured the hormone concentrations in the plasma of the patients after 4 hours of fasting.

The results showed that the levels of glucagon and insulin were significantly lower in patients with VLCAD deficiency compared to those with carnitine uptake deficiency. The concentration of glucagon in patients with carnitine uptake deficiency was similar to the normative data. 

In contrast, there were no significant differences between the groups of patients in terms of glucagon-like peptide 1 (GLP-1), which inhibits the secretion of glucagon; glicentin, which stimulates the secretion of insulin; glucose; amino acids; or non-esterified fatty acids (NEFAs). 

“In conclusion, the fasting glucagon concentrations are lowered in patients with VLCAD deficiency, and this is likely driven by the defect of [fatty-acid oxidation] in itself rather than altered factors in the plasma,” the researchers wrote. “These results are compatible with α-cell fatty acid β-oxidation being central to appropriate hormonal secretion during fasting.”


Stenlid R, Manell H, Seth R, et al. Low fasting concentrations of glucagon in patients with very long-chain acyl-CoA dehydrogenase deficiency. Metabolites. 2023;22;13(7):780. doi:10.3390/metabo13070780