Plasma and urine metabolic profiles are reflective of altered beta-oxidation in non-diabetic obese subjects and patients with type 2 diabetes mellitus.
OBJECTIVE
The two primary pathophysiological characteristics of patients with type 2 diabetes mellitus (T2DM) are insulin resistance (IR) and beta cell dysfunction. It has been proposed that the development of IR is secondary to the accumulation of triacylglycerols and fatty acids in the muscle and liver, which is in turn thought to be secondary to an enzymatic defect in mitochondrial beta-oxidation. The purpose of the present study was to analyze the molecules of intermediary metabolism to determine if an alteration in mitochondrial function exists in T2DM patients and, if so, to determine whether this alteration is caused by excess nutrients or an enzymatic defect.


METHODS
Seventy-seven subjects were recruited and divided into four groups (21 T2DM patients, 17 non-diabetic overweight/obese subjects, 20 offspring of T2DM patients, and 19 healthy subjects). Anthropometric parameters were determined by air plethysmography, and biochemical and metabolic parameters were measured, including 31 acylcarnitines (ACs) and 13 amino acids quantified by MS/MS and 67 organic acids measured by GC/MS.


RESULTS
Patients with T2DM showed elevation of short-chain ACs (C2, C4), a glycogenic amino acid (valine), a glycogenic and ketogenic amino acid (tyrosine), and a ketogenic amino acid (leucine) as well as altered excretion of dicarboxylic acids. T2DM offspring with abnormal glucose tolerance test GTT showed increased levels of C16. Subjects in the obese group who were dysglycemic also showed altered urinary excretion of dicarboxylic acids and lower levels of a long-chain AC (C14:2).


CONCLUSIONS
These results suggest that mitochondrial beta-oxidation is altered in T2DM patients and that the alteration is most likely caused by nutrient overload through a different pathway from that observed in obese subjects.
Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Servicio de Endocrinología, Monterrey, Nuevo León, 64460 México.
Jesús Zacarías
JZ
Villarreal-Pérez
Departamento de Medicina Interna, Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Monterrey, Nuevo León 64460 México.
Jesús Zacarías
JZ
Villarreal-Martínez
Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Servicio de Endocrinología, Monterrey, Nuevo León, 64460 México.
Fernando Javier
FJ
Lavalle-González
Departamento de Genética, Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Av. Gonzalitos s/n, Colonia Mitras Centro, Monterrey, Nuevo León 64460 México.
María Del Rosario
Mdel R
Torres-Sepúlveda
Departamento de Genética, Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Av. Gonzalitos s/n, Colonia Mitras Centro, Monterrey, Nuevo León 64460 México.
Consuelo
C
Ruiz-Herrera
Universidad Autónoma de Nuevo León, Facultad de Enfermería, Avenida Gonzalitos, 1500 Norte, Col. Mitras Centro, Monterrey, NL México.
Ricardo Martín
RM
Cerda-Flores
Departamento de Genética, Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Av. Gonzalitos s/n, Colonia Mitras Centro, Monterrey, Nuevo León 64460 México.
Erik Rubén
ER
Castillo-García
Departamento de Genética, Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Av. Gonzalitos s/n, Colonia Mitras Centro, Monterrey, Nuevo León 64460 México.
Irám Pablo
IP
Rodríguez-Sánchez
Departamento de Genética, Universidad Autónoma de Nuevo León, Hospital Universitario, "Dr. José Eleuterio González", Av. Gonzalitos s/n, Colonia Mitras Centro, Monterrey, Nuevo León 64460 México.
Laura Elia
LE
Martínez de Villarreal
Acetylcarnitine; Air plethysmography; Beta-oxidation defect; Butyrylcarnitine; Non-diabetic obese; T2DM