Background: Friedreich’s Ataxia (FA) is a neuromuscular disorder caused by either GAA triplet repeat expansions of both alleles of the gene frataxin, or less commonly, by a point mutation in one allele and triplet expansion on the other. FA is associated with an increased incidence of diabetes (DM), but risk factors and management are not well described.
Objective: To report the prevalence of, identify risk factors for, and describe management of DM in FA using the large (N=1,020) multi-site, longitudinal, observational FA Outcomes Measures Study (FACOMS).
Methods: FACOMS was queried for self-reported DM status and the modified FA Rating Scale (mFARS), which rates severity. For the subset at the Children’s Hospital of Philadelphia (CHOP), past medications were noted via EMR. Point mutation status and mFARS were compared in DM vs. non DM with chi-square and Wilcoxon signed rank tests, respectively. Independent risk factors for DM were tested by logistic regression including mFARS, age, point mutation, and age of FA diagnosis (dx).
Results: Median age of FA dx was 14y (IQR 10-21), 5.7% had a point mutation, and 8.8% had DM. In those with DM, median age at DM dx was 27y (IQR 17-41) and mean HbA1c since dx was 7% (SD 1). Point mutations were more common in DM vs. non DM (13.9% vs. 4.9%; p<0.001). Those with DM had more severe disease (median mFARS, 70, IQR 58,78) vs. without (55, IQR 41,68) (p<0.001). In logistic regression, severe disease (mFARS 4th vs. 1st quartile, OR 4.54, 95%CI: 1.75,11.77, p=0.002), older age (OR 1.05, 95%CI: 1.02,1.07, p<0.001), and point mutation (OR 4.49, 95%CI: 2.11,9.53, p<0.001) were associated with a greater risk of DM. In FACOMS, 76% (61/80 with DM and current medication data) used insulin. At CHOP, 47% (14/30 with DM and past medication data) had ever tried Metformin.
Conclusions: DM in FA was associated with more severe disease, older age, and a point mutation. Many require insulin. Future studies will evaluate the pathophysiology of FA-related DM to inform screening practices and management decisions.
J. Tamaroff: None. A. DeDio: None. K.L. Wade: None. C. Rummey: None. S.E. Pinney: None. D. Lynch: None. A. Kelly: None. S. McCormack: Advisory Panel; Self; Reata Pharmaceuticals, Rhythm Pharmaceuticals. Other Relationship; Self; Levo Pharmaceuticals.
National Institutes of Health (T32DK063688-16); Uplifting Athletes; McCormack Children’s Hospital of Pittsburgh Metabolism, Nutrition, and Development Research Affinity Group; McCormack Friedreich’s Ataxia Research Alliance