Similarities in Serum Acylcarnitine Patterns in Type 1 and Type 2 Diabetes Mellitus and in Metabolic Syndrome

Abstract

Background/Aims: In type 1 diabetes (T1D), type 2 diabetes (T2D) and metabolic syndrome (MetS), the associated complex metabolomic changes in the involvement of carnitine metabolism in total carnitine ester level has already been documented; here we extended the investigations to the individual acylcarnitines. Methods: The fasting serum acylcarnitine concentrations were determined in 49 T1D, 38 T2D and 38 MetS patients and 40 controls by isotope dilution electrospray ionization tandem mass spectrometry. Results: The acylcarnitine profiles of the 3patient groups shared elements with the controls. Considerably higher levels of almost all short-chain acylcarnitines (p < 0.05) and lower levels of some long-chain acylcarnitines were detected in T2D and MetS patients. The amounts of C3 and C4 carnitine were higher and most of the medium-chain and long-chain acylcarnitine levels were lower (p < 0.05) in T1D and MetS patients than in the controls. In T1D and T2D, the levels of C3 and C4 acylcarnitines were markedly elevated and some long-chain acylcarnitines were lower than the controls (p < 0.05). Moreover, significantly lower concentrations of free- and total carnitine were observed in T1D patients (p < 0.05). Conclusions: Profound alterations were detected in acylcarnitine profiles in the 3 patient groups. Similarities in the patterns suggest different degrees of involvement of the same metabolic systems in a systems biology approach.

Alterations of plasma metabolite profiles related to adipose tissue distribution and cardiometabolic risk

“…Altered plasma AA, and AA-related catabolic products such as 2-aminoadipic acid (2-AAA), Kyn, and C5 acylcarnitine were also related to insulin resistance. This result is consistent with previous studies reporting impaired AA, and especially BCAA metabolism, in obese and insulinresistant subjects (4,8,33,51). Interestingly, our results suggest that the association between plasma BCAA and obesity is independent of insulin resistance level assessed by HOMA-IR.…”

The Mitochondria in Diabetic Heart Failure: From Pathogenesis to Therapeutic Promise

“…The backlog of these metabolites can be toxic to the cell and may contribute to cardiomyocyte death and dysfunction. Consistent with the concept of imbalance between b-oxidation and mitochondrial respiration, FAO intermediates, such as acylcarnitines, are elevated in animal models and humans with diabetes (11,73,91).…”

CoA protects against the deleterious effects of caloric overload in Drosophila

“…It follows that these acyl-carnitines might accumulate when metabolic fl ux is reduced during insulin resistance. Increased long-chain carnitine esters have been observed in the serum, liver, muscle, and urine of individuals with obesity and T2D (41)(42)(43)(44)(45)(46), although reduced levels of long-chain acyl-carnitines have also been associated with metabolic syndrome and T2D ( 47 ). Rodent models of obesity and T2D also accumulate acyl-carnitines (48)(49)(50).…”