Dataset Information

Effects of genetic severity on glucose homeostasis in Friedreich ataxia.

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.

SUBMITTER: Isaacs CJ

PROVIDER: S-EPMC5257251 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of genetic severity on glucose homeostasis in Friedreich ataxia.

Isaacs Charles J CJ Brigatti Karlla W KW Kucheruk Olena O Ratcliffe Sarah S Sciascia Tom T McCormack Shana E SE Willi Steven M SM Lynch David R DR

Muscle & nerve 20160830 5

<h4>Introduction</h4>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.<h4>Methods</h4>To examine these dynamics, we analyzed oral and intravenous glucose tolerance test data in 42 non-diabetic patients with FRDA.<h4>Results</h4>Patients showed high insulin responsiveness to glucose and low insulin sensitivit ...[more]

PMID: 27061687

Similar Datasets

Project description:INTRODUCTION:Although a concentric pattern of left ventricular (LV) geometry appears to be common in Friedreich ataxia (FRDA), there is no accepted method for diagnosing LV abnormalities in FRDA, sex and body size have often not been taken into consideration, and it has not been clear whether children and adults should be classified using the same criteria. The aim of this study was to better define the LV geometric changes in FRDA with respect to sex, body size and subject age, and to investigate the relationship of LV changes with genetic severity, as assessed by GAA repeat length within the shorter allele of the FXN gene (GAA1). METHODS:Echocardiography was performed in 216 subjects (68 children, 148 adults), measurements were made at end-diastole of LV internal diameter (LVEDID), septal wall thickness (SWT), LV length (LVEDL) and LV volume (LVEDV), and calculations were made of relative wall thickness (RWT), LV mass and LV ejection fraction (LVEF). RESULTS:The most common LV abnormalities in both adults and children with FRDA were increases in RWT and age-normalized RWT. In adults with a normal LVEF, all LV variables other than RWT were larger in males independent of body surface area (BSA), and all LV variables other than SWT and RWT were positively correlated with BSA. After adjustment for sex and BSA, GAA1 was a positive correlate of SWT and RWT (but not of LV mass), and was an inverse correlate of LVEDID, LVEDL and LVEDV. In children with a normal LVEF, SWT, LV mass and LVEDL were larger in males than females after adjusting for BSA, and in combination with sex, BSA was a positive correlate of all the LV variables except SWT and RWT. In children there were no correlations of GAA1 with any of the LV variables. CONCLUSION:In FRDA, increases in RWT and age-normalized RWT are the most frequent LV structural abnormalities, sex and body size are important determinants of most other LV structural variables in both children and adults, and increased genetic severity is associated with a smaller left ventricle and increased LV wall thickness in adults, but not associated with LV size or wall thickness in children.

Dataset Information

Effects of genetic severity on glucose homeostasis in Friedreich ataxia.

Publications

Effects of genetic severity on glucose homeostasis in Friedreich ataxia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets