RESUMO
OBJECTIVES: To evaluate the relationship between disease features in Friedreich ataxia and aberrant glucose metabolism. METHODS: Fasting glucose, fasting insulin and random HbA1C were obtained in 158 patients with Friedreich ataxia. Regression analysis evaluated glucose, insulin, and homeostatic model assessment (HOMA) of insulin resistance (IR) and beta-cell function (ß) in relation to age, BMI, sex, and genetic severity. Categorical glucose values were analyzed in relation to other FRDA-associated disease characteristics. RESULTS: In the FRDA cohort, age and GAA repeat length predicted fasting glucose and HbA1c levels (accounting for sex and BMI), while insulin and HOMA-IR were not predicted by these parameters. Within the cohort, average BMI was consistently lower than the national average by age and was marginally associated with insulin levels and HOMA-IR. Within juvenile subjects, insulin and HOMA-IR were predicted by age. Controlling for age and genetic severity, diabetes-related measures were not independent predictors of any quantitative measure of disease severity in FRDA. Glucose handling properties were also predicted by the presence of a point mutation, with 40% of individuals heterozygous for point mutations having diabetes, compared to 4.3% of subjects who carried two expanded GAA repeats. INTERPRETATION: In FRDA, aberrant glucose metabolism is linked to increasing age, longer GAA repeat length on the shorter allele, frataxin point mutations, and increasing BMI. The effect of age to some degree may be mediated through changes in BMI, with increasing age associated with increases in BMI, and with HOMA-IR and insulin increases in children.
Assuntos
Glicemia/metabolismo , Ataxia de Friedreich/metabolismo , Homeostase , Adolescente , Adulto , Fatores Etários , Idoso , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Jejum/sangue , Feminino , Ataxia de Friedreich/sangue , Ataxia de Friedreich/complicações , Ataxia de Friedreich/genética , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Proteínas de Ligação ao Ferro/genética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Mutação Puntual/genética , Fatores Sexuais , Expansão das Repetições de Trinucleotídeos/genética , Adulto Jovem , FrataxinaRESUMO
BACKGROUND: Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, areflexia, and cardiomyopathy. At present, baseline values of cardiac troponin I are unknown among Friedreich ataxia subjects. METHODS: In this study, we evaluated baseline plasma cardiac troponin I levels among a cross-sectional cohort of 49 pediatric and adult Friedreich ataxia subjects without active arrhythmia, chest pain or features of acute coronary syndrome at the time of sampling. We also reviewed baseline electrocardiograms from 45 of these subjects. RESULTS: Troponin I values were elevated above the 99th percentile population cutoff in 46.9% of all subjects, with 16.3% of asymptomatic subjects having levels typically seen during an acute myocardial infarction. In logistic regression models, younger age and an earlier disease onset predicted higher serum cardiac troponin I values. Only weak correlations were seen between cardiac troponin I values and echocardiogram parameters, including ejection fraction. Additionally, 82.2% of subjects also had abnormal baseline electrocardiograms. CONCLUSION: The present study demonstrates that both abnormal electrocardiograms and elevated serum cardiac troponin I values may be common baseline characteristics seen in Friedreich ataxia subjects. Further longitudinal studies will allow for a better understanding of the cause and prognostic implications of elevated levels, as well as the clinical utility of serum cardiac troponin I testing in Friedreich ataxia.
