Impact of Diabetes in the Friedreich Ataxia Clinical Outcome Measures Study

Objective: Friedreich ataxia (FA) is a progressive neuromuscular disorder caused by GAA triplet repeat expansions or point mutations in the gene. FA is associated with increased risk of diabetes mellitus (DM). This study assessed the age-specific prevalence of FA-associated DM and its impact on neurologic outcomes.

Research Design And Methods: Participants were 811 individuals with FA from 12 international sites in a prospective natural history study (FA Clinical Outcome Measures Study, FACOMS). Physical function was assessed, using validated instruments. Multivariable regression analyses examined the independent association of DM with outcomes.

Results: Mean age of participants was 30.1 years (SD 15.3, range: 7-82), 50% were female, and 94% were non-Hispanic white. 9% (42/459) of adults and 3% (10/352) of children had DM. Individuals with FA-associated DM were older ( < 0.001), had longer GAA repeat length on the least affected allele ( = 0.037), and more severe FA ( = 0.0001). Of individuals with DM, 65% (34/52) were taking insulin. Even after accounting statistically for both age and GAA repeat length, DM was independently associated with greater FA symptom burden ( = 0.010), reduced capacity to perform activities of daily living ( = 0.021), and a decrease of 0.33 SDs on a composite performance measure (95% CI: -0.56-0.11, = 0.004); the relative impact of DM was most apparent in younger individuals.

Conclusions: DM-associated FA has an independent adverse impact on well-being in affected individuals, particularly at younger ages. In future, evidence-based approaches for identification and management of FA-related DM may improve both health and function.