Evidence of Insulin Resistance and Other Metabolic Alterations in Boys with Duchenne or Becker Muscular Dystrophy

Maricela Rodríguez-Cruz, Raúl Sanchez, Rosa E Escobar, Oriana Del Rocío Cruz-Guzmán, Mardia López-Alarcón, Mariela Bernabe García, Ramón Coral-Vázquez, Guadalupe Matute, Ana Claudia Velázquez Wong, Maricela Rodríguez-Cruz, Raúl Sanchez, Rosa E Escobar, Oriana Del Rocío Cruz-Guzmán, Mardia López-Alarcón, Mariela Bernabe García, Ramón Coral-Vázquez, Guadalupe Matute, Ana Claudia Velázquez Wong

Abstract

Aim. Our aim was (1) to determine the frequency of insulin resistance (IR) in patients with Duchenne/Becker muscular dystrophy (DMD/BMD), (2) to identify deleted exons of DMD gene associated with obesity and IR, and (3) to explore some likely molecular mechanisms leading to IR. Materials and Methods. In 66 patients with DMD/BMD without corticosteroids treatment, IR, obesity, and body fat mass were evaluated. Molecules involved in glucose metabolism were analyzed in muscle biopsies. Results show that 18.3%, 22.7%, and 68% were underweight, overweight, or obese, and with high adiposity, respectively; 48.5% and 36.4% presented hyperinsulinemia and IR, respectively. Underweight patients (27.3%) exhibited hyperinsulinemia and IR. Carriers of deletions in exons 45 (OR = 9.32; 95% CI = 1.16-74.69) and 50 (OR = 8.73; 95% CI = 1.17-65.10) from DMD gene presented higher risk for IR than noncarriers. We observed a greater staining of cytoplasmic aggregates for GLUT4 in muscle biopsies than healthy muscle tissue. Conclusion. Obesity, hyperinsulinemia, and IR were observed in DMD/BMD patients and are independent of corticosteroids treatment. Carriers of deletion in exons 45 or 50 from DMD gene are at risk for developing IR. It is suggested that alteration in GLUT4 in muscle fibers from DMD patients could be involved in IR.

Figures

Figure 1
Figure 1
Distribution of the mutations detected in the DMD gene in patients with Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD).
Figure 2
Figure 2
Scatter plot of body fat mass and HOMA-IR in DMD/BMD patients. HOMA-IR, homeostasis model assessment-insulin resistance.
Figure 3
Figure 3
Risk of developing insulin resistance (homeostasis model assessment-insulin resistance > 3.16). P values and odds ratio calculated by logistic regression model. CI, confidence interval. Data adjusted by % body fat mass. E = Exon.
Figure 4
Figure 4
Immunofluorescence analysis of dystrophin (DYS), insulin receptor (IRe), insulin receptor substrate (IRS), and glucose transporter 4 (GLUT4) of healthy individuals and DMD/BMD patients. Immunostaining demonstrated semiabsence of dystrophin on the muscle fibers of the patients. DYS-C, GLUT4, IRe, and IRS are stained in red (arrows) and nuclei are stained in blue (n). Negative control omitted the primary antibody.

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