title: Effects of genetic severity on glucose homeostasis in Friedreich ataxia.
abstract: Friedreich ataxia (FRDA) leads to increased risk of diabetes. Less is known regarding the dynamics of glucose homeostasis in FRDA, the influence of disease features, and the utility of oral-based metrics for capturing metabolic dysfunction.
  
  
  
  To examine these dynamics, we analyzed oral and intravenous glucose tolerance test data in 42 non-diabetic patients with FRDA.
  
  
  
  Patients showed high insulin responsiveness to glucose and low insulin sensitivity. Genetic severity predicted overall metabolic impairment: individuals with longer guanine-adenine-adenine (GAA) repeats on the shorter allele showed a lower disposition index. Genetic severity did not predict any other variables. Measures of disposition index from intravenous and oral glucose tolerance testing did not correlate well, possibly reflecting divergent responses to oral and intravenous glucose loads.
  
  
  
  FRDA patients demonstrate abnormal compensatory activity for managing glucose. Genetic severity impacts the global homeostatic profile, whereas relative contributions of insulin secretion and action vary from patient to patient. Muscle Nerve 54: 887-894, 2016.
authors.affiliation: Division of Neurology, The Children's Hospital of Philadelphia, 502 Abramson Research Center, Philadelphia, 3615 Civic Center Boulevard, Pennsylvania, 19104-4318, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Isaacs
authors.affiliation: Division of Neurology, The Children's Hospital of Philadelphia, 502 Abramson Research Center, Philadelphia, 3615 Civic Center Boulevard, Pennsylvania, 19104-4318, USA.
authors.forename: Karlla W
authors.initials: KW
authors.lastname: Brigatti
authors.affiliation: Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennyslvania, USA.
authors.forename: Olena
authors.initials: O
authors.lastname: Kucheruk
authors.affiliation: Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennyslvania, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ratcliffe
authors.affiliation: Penwest Pharmaceuticals, New York, New York, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Sciascia
authors.affiliation: Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennyslvania, USA.
authors.forename: Shana E
authors.initials: SE
authors.lastname: McCormack
authors.affiliation: Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennyslvania, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Willi
authors.affiliation: Division of Neurology, The Children's Hospital of Philadelphia, 502 Abramson Research Center, Philadelphia, 3615 Civic Center Boulevard, Pennsylvania, 19104-4318, USA. lynchd@mail.med.upenn.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Lynch
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D005621:Friedreich Ataxia / Q000150:complications* / Q000235:genetics*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D008659:Metabolic Diseases / Q000209:etiology*; D008875:Middle Aged; D012044:Regression Analysis; D012720:Severity of Illness Index; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*; D055815:Young Adult; D000096923:Frataxin
chemical_list: D005947:Glucose; D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: Friedreich ataxia; diabetes mellitus; glucose homeostasis; glucose metabolism; neurodegenerative disease