Altered Serum Amino Acid and Acylcarnitine Profiles in Hyperinsulinemic Hypoglycemia and Ketotic Hypoglycemia

Abstract

Background In addition to inborn metabolic disorders, altered metabolic profiles were reported to be associated with the risk and prognosis of some non-metabolic diseases, while as a rare metabolic disease, the overall secondary metabolic spectrum in congenital hyperinsulinemic hypoglycemia (HH) is largely undetermined. Therefore, we investigated metabolic profiles in HH patients and used ketotic hypoglycemia (KH) patients as a control cohort to unveil their distinct metabolic features. Methods A total of 97 hypoglycemia children, including 74 with hyperinsulinemic hypoglycemia and 23 with ketotic hypoglycemia, and 170 euglycemia control subjects were studied retrospectively. Clinical and biochemical data were collected. The normoglycemic spectra of amino acids and acylcarnitines were determined by liquid chromatography tandem mass spectrometry. The serum insulin and fatty acid concentrations during standardized fasting tests in hypoglycemia patients were also collected. Receiver operating characteristic curve analysis was performed to screen potential biomarkers. Results Among the normoglycemic spectra of amino acids, blood valine ( p < 0.001), arginine ( p < 0.001), threonine ( p = 0.001), glutamate ( p = 0.002), methionine ( p = 0.005), ornithine ( p = 0.008), leucine ( p = 0.014), alanine ( p = 0.017), proline ( p = 0.031), citrulline ( p = 0.042), aspartate ( p = 0.046), and glycine ( p = 0.048) levels differed significantly among the three groups. Significantly decreased levels of long- (C14:1, p < 0.001; C18, p < 0.001), medium- (C8, p < 0.001; C10, p < 0.001; C10:1, p < 0.001), and short-chain (C4-OH, p < 0.001; C5OH, p < 0.001) acylcarnitines were found in the hyperinsulinemic hypoglycemia group. Hyperinsulinemic hypoglycemia children with focal lesions and diffuse lesions had similar amino acid and acylcarnitine spectra. C10:1 < 0.09 μmol/L, threonine > 35 μmol/L, and threonine/C10:1 > 440 showed sensitivities of 81.1, 66.2, and 81.1% and specificities of 72.7, 78.3, and 81.8%, respectively, in distinguishing HH from KH. Conclusions We found significantly different altered serum amino acid and acylcarnitine profiles at normoglycemia, especially decreased C10:1 and increased threonine levels, between HH and KH children, which may reflect the insulin ketogenesis inhibition effect in HH patients; however, the detailed mechanisms and physiological roles remain to be studied in the future.

Exogenous Substrates Prevent the Decline in the Cellular ATP Content of Primary Rat Astrocytes During Glucose Deprivation

“…The sources of extracellular proline in brain that could be metabolised by astrocytes remains to be identified. The concentration of proline in human serum has been reported to be in the higher micromolar range (170 µM [ 61 ], 450 µM [ 62 ]), while only 6 µM proline have been determined for cerebrospinal fluid [ 61 ], suggesting that peripheral proline may be one proline source for astrocytes. Further studies are now required to elucidate in detail the proline metabolism of astrocytes and of other brain cells, especially considering that proline has well known behavioral and neurochemical effects [ 63 ] and that the proline metabolism is strongly connected to neurological and psychiatric disorders [ 49 ].…”

A nomogram based on metabolic profiling to discriminate lung cancer among patients with lung nodules

“…The function of carnitines is to bring long-chain fatty acids into the mitochondria for β-oxidation, followed by the formation of acylcarnitine, excess of which is subsequently released into the bloodstream. 9 In lung cancer, the de novo synthesis of fatty acids is closely related to the proliferation and metastasis of cancer cells. 10 Therefore, the acylcarnitine profile in lung cancer can reflect the metabolic status of fatty acids.…”

“… 8 For example, the function of carnitine is to bring long-chain fatty acids into the mitochondria for β-oxidation, followed by the formation of acylcarnitine, an excess of which is then released into the bloodstream. 9 In lung cancer, the acylcarnitine profile can reflect the metabolic status of fatty acids, as the de novo synthesis of fatty acids is closely related to the proliferation and metastasis of tumor cells. 10 Accordingly, amino acids and carnitines are potential biomarkers for diagnosing cancer, as they serve essential roles in cell physiology as both basic metabolites and metabolic regulators.…”

Profiles of Amino Acids and Acylcarnitines Related with Deltamethrin Resistance in Aedes Albopictus

“…Metabolomics could re ect systematic human metabolic variations in accordance with phenotypic changes, such as resistance to insulin [12] and trastuzumab [13]. Characteristic of amino acids and AcylCNs acylcarnitine pro le has become is a powerful and popular tool for diagnostic of clinical metabolic alterations [14][15][16][17][18]. However, little is known of the characteristic of amino acids and AcylCNs pro les in mosquitoes.…”