Charles J Isaacs1, Karlla W Brigatti1, Olena Kucheruk2, Sarah Ratcliffe2, Tom Sciascia3, Shana E McCormack2, Steven M Willi2, David R Lynch4. 1. Division of Neurology, The Children's Hospital of Philadelphia, 502 Abramson Research Center, Philadelphia, 3615 Civic Center Boulevard, Pennsylvania, 19104-4318, USA. 2. Division of Endocrinology/Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennyslvania, USA. 3. Penwest Pharmaceuticals, New York, New York, USA. 4. 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.
Abstract
INTRODUCTION: 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. METHODS: To examine these dynamics, we analyzed oral and intravenous glucose tolerance test data in 42 non-diabetic patients with FRDA. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: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. METHODS: To examine these dynamics, we analyzed oral and intravenous glucose tolerance test data in 42 non-diabeticpatients with FRDA. RESULTS: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. CONCLUSIONS:FRDApatients 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.
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