Dyslipidemia in Muscular Dystrophy: A Systematic Review and Meta-Analysis

Abstract

Background: Muscular dystrophies (MDs) are characterized by chronic muscle wasting but also poorly understood metabolic co-morbidities. We have recently shown that Duchenne MD (DMD) patients, dogs and asymptomatic carriers are affected by a new form of dyslipidemia that may exacerbate muscle damage. Objective: We aimed to perform a systematic review and meta-analysis for evidence that other types of MDs are associated with dyslipidemia compared to healthy controls. Methods: Search was conducted using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials for reports that compare plasma/serum lipids from MD patients and controls, and meta-analysis of cross-sectional studies quantifying total cholesterol, high-density lipoprotein, low density lipoprotein and triglycerides was performed. Results: Out of 749 studies, 17 met our inclusion criteria for meta-analysis. 14 of the 17 studies (82% ) included investigated myotonic dystrophy (DM); other studies were on pseudohypertrophic MD (PMD) or DMD. As a whole, MD individuals had significantly higher levels of circulating total cholesterol (Hedges’ g with 95% confidence interval [CI], 0.80 [0.03 – 1.56]; p = 0.04) and triglycerides (Hedges’ g with 95% confidence interval [CI], 2.28[0.63 – 3.92]; p = 0.01) compared to controls. Meta-regression analysis showed the percentage of male gender was significantly associated with the difference in total cholesterol (beta = 0.05; 95% CI, – 0.02 to 0.11; p = 0.043) and high-density lipoprotein (beta = – 9.38; 95% CI, – 16.26 to – 2.50; p = 0.028). Conclusions: MD is associated with significantly higher circulating levels of total cholesterol and triglycerides. However, caution on the interpretation of these findings is warranted and future longitudinal research is required to better understand this relationship.

Humanization of the mdx Mouse Phenotype for Duchenne Muscular Dystrophy Modeling: A Metabolic Perspective

“…Dysregulation of miRNAs associated with lipid metabolism and cholesterol synthesis has been documented as a potential cause of muscle wasting in DMD [69]. Hence, DMD is associated with defects in both circulating lipoprotein and intramyofiber cholesterol homeostasis, as confirmed in a systematic review and meta-analysis [76]. As this metabolic co-morbidity may exacerbate the primary muscle defect [68], this supports the use of transgenic strains with altered lipoprotein metabolism to generate more human-relevant mdx model.…”