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. 2023 Jun 22;13(7):780.
doi: 10.3390/metabo13070780.

Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

Rasmus Stenlid  1 , Hannes Manell  2 , Rikard Seth  1 , Sara Y Cerenius  1 , Azazul Chowdhury  1 , Camilla Roa Cortés  1 , Isabelle Nyqvist  1 , Thomas Lundqvist  3 , Maria Halldin  3 , Peter Bergsten  1
Affiliations

Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

Rasmus Stenlid et al. Metabolites. .

Abstract

(1) Background: Deficiencies of mitochondrial fatty acid oxidation (FAO) define a subgroup of inborn errors of metabolism, with medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) being two of the most common. Hypoketotic hypoglycemia is a feared clinical complication and the treatment focuses on avoiding hypoglycemia. In contrast, carnitine uptake deficiency (CUD) is treated as a mild disease without significant effects on FAO. Impaired FAO has experimentally been shown to impair glucagon secretion. Glucagon is an important glucose-mobilizing hormone. If and how glucagon is affected in patients with VLCAD or MCAD remains unknown. (2) Methods: A cross-sectional study was performed with plasma hormone concentrations quantified after four hours of fasting. Patients with VLCAD (n = 10), MCAD (n = 7) and CUD (n = 6) were included. (3) Results: The groups were similar in age, sex, weight, and height. The glucagon and insulin levels were significantly lower in the VLCAD group compared to the CUD group (p < 0.05, respectively). The patients with CUD had glucagon concentrations similar to the normative data. No significant differences were seen in GLP-1, glicentin, glucose, amino acids, or NEFAs. (4) Conclusions: Low fasting concentrations of glucagon are present in patients with VLCAD and cannot be explained by altered stimuli in plasma.

Keywords: carnitine uptake deficiency; glucagon; glucagon like peptide-1; inborn errors of metabolism; insulin; medium-chain acyl-CoA dehydrogenase deficiency; pediatrics; very long-chain acyl-CoA dehydrogenase deficiency.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Fasting plasma concentrations of glucagon in patients with carnitine uptake deficiency (CUD, n = 5), medium-chain acyl-CoA dehydrogenase deficiency (MCAD, n = 7), and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD, n = 10). The lower limit of detection (LOD) was 1.5 pmol/L. Each black point represents an individual patient. Note: * = p < 0.05.
Figure 2
Figure 2
Fasting plasma concentrations of glucose (a), amino acids (b), and non-esterified fatty acids (NEFA) (c) in patients with carnitine uptake deficiency (CUD, n = 6), medium-chain acyl-CoA dehydrogenase deficiency (MCAD, n = 7), and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD, n = 10). For the amino acids, n = −1 for each group. Each black point represents an individual patient.
Figure 3
Figure 3
Fasting plasma concentrations of insulin (a), glucagon-like peptide 1 (GLP-1) (b), and glicentin (c) in patients with carnitine uptake deficiency (CUD, n = 6), medium-chain acyl-CoA dehydrogenase deficiency (MCAD, n = 7), and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD, n = 10). For insulin, n = −1 in the MCAD and VLCAD group. For glicentin, n = −1 in the CUD group. Each black point represents an individual patient. Note: * = p < 0.05.
Figure 4
Figure 4
Fasting plasma concentrations of glucagon (a) and insulin (b) in patients with carnitine uptake deficiency (CUD, n = 6), medium-chain acyl-CoA dehydrogenase deficiency (MCAD, n = 7), and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD, n = 10). Statistical outliers included. The lower limit of detection (LOD) for glucagon was 1.5 pmol/L. Each black point represents an individual patient. Note: ** = p < 0.01.
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