Aniridics with PAX-6 Mutations Display Elevated BMI and Impaired GLP-1 Response
Poster #: 098
Session/Time: A
Author:
Sravani Sunkara, BS
Mentor:
Peter A. Netland, MD, PhD
Research Type: Clinical Research
Abstract
INTRODUCTION:
Aniridia is a rare, congenital eye disorder characterized by hypoplasia or aplasia of the iris. Aniridia occurs approximately every 1.8/100,000 live births. Both familial and sporadic aniridia are caused by heterozygous mutations in the paired box 6 (PAX6) gene on chromosome 11. PAX6 is a key transcription factor in the development of the eye, pancreas, and brain. In the eye, PAX6 mutations are associated with panocular issues, such as nystagmus, foveal hypoplasia, aniridia-associated keratopathy, and cataracts. The literature indicates that PAX6 mutations are associated with metabolic changes, including pro-insulinemia and impaired glucose tolerance. This study aims to explore metabolic differences between aniridics with PAX6 mutations and their relatives without PAX6 mutations by assessing Body Mass Index (BMI) and pre-prandial to post-prandial Glucagon-Like Peptide-1 (GLP-1) percent changes.
METHODS:
This study is a prospective case-control study of 12 aniridics and 12 controls. The control group consists of non-aniridic relatives of the aniridics in the study. Data collection comprised blood draws, demographics, and physical measurements at the 2013 Aniridia Foundation International meeting. Blood was drawn from each study participant before and after the participants consumed a glucose solution (Ensure Nutrition Shake with 33 grams of glucose). Next, the blood samples underwent laboratory analysis of various aspects, including GLP-1, Hemoglobin A1C (HbA1C), glucose, insulin, ghrelin, and glucagon levels. After the blood sample results were processed, the data were statistically analyzed. BMI differences between aniridics and controls were assessed using an independent t-test. Due to the small sample size, paired data, and outliers, the Wilcoxon test was chosen to analyze the % change in pre-prandial to post-prandial GLP-1 in obese (BMI≥30) aniridics and obese controls.
RESULTS:
The independent t-test showed aniridics displayed significantly higher BMIs than controls (p=0.009). The Wilcoxon test showed obese aniridics had a significantly lower percent increase in pre-prandial to post-prandial GLP-1 compared to controls (p-value=0.035).
CONCLUSION:
The results suggest aniridics may have impaired GLP-1 release in response to meals compared to controls. As GLP-1 is a satiety hormone that suppresses appetite, this may contribute to aniridics having higher BMIs than controls. These findings, coupled with the existing literature stating that aniridics display higher glucose intolerance compared with controls, demonstrate that aniridia may be associated with metabolic abnormalities. Due to this study's small sample size and large variability in participants' ages, further studies with larger sample sizes and less participant age variability are recommended to explore the role of PAX6 in obesity and post-prandial GLP-1 release.
Aniridia is a rare, congenital eye disorder characterized by hypoplasia or aplasia of the iris. Aniridia occurs approximately every 1.8/100,000 live births. Both familial and sporadic aniridia are caused by heterozygous mutations in the paired box 6 (PAX6) gene on chromosome 11. PAX6 is a key transcription factor in the development of the eye, pancreas, and brain. In the eye, PAX6 mutations are associated with panocular issues, such as nystagmus, foveal hypoplasia, aniridia-associated keratopathy, and cataracts. The literature indicates that PAX6 mutations are associated with metabolic changes, including pro-insulinemia and impaired glucose tolerance. This study aims to explore metabolic differences between aniridics with PAX6 mutations and their relatives without PAX6 mutations by assessing Body Mass Index (BMI) and pre-prandial to post-prandial Glucagon-Like Peptide-1 (GLP-1) percent changes.
METHODS:
This study is a prospective case-control study of 12 aniridics and 12 controls. The control group consists of non-aniridic relatives of the aniridics in the study. Data collection comprised blood draws, demographics, and physical measurements at the 2013 Aniridia Foundation International meeting. Blood was drawn from each study participant before and after the participants consumed a glucose solution (Ensure Nutrition Shake with 33 grams of glucose). Next, the blood samples underwent laboratory analysis of various aspects, including GLP-1, Hemoglobin A1C (HbA1C), glucose, insulin, ghrelin, and glucagon levels. After the blood sample results were processed, the data were statistically analyzed. BMI differences between aniridics and controls were assessed using an independent t-test. Due to the small sample size, paired data, and outliers, the Wilcoxon test was chosen to analyze the % change in pre-prandial to post-prandial GLP-1 in obese (BMI≥30) aniridics and obese controls.
RESULTS:
The independent t-test showed aniridics displayed significantly higher BMIs than controls (p=0.009). The Wilcoxon test showed obese aniridics had a significantly lower percent increase in pre-prandial to post-prandial GLP-1 compared to controls (p-value=0.035).
CONCLUSION:
The results suggest aniridics may have impaired GLP-1 release in response to meals compared to controls. As GLP-1 is a satiety hormone that suppresses appetite, this may contribute to aniridics having higher BMIs than controls. These findings, coupled with the existing literature stating that aniridics display higher glucose intolerance compared with controls, demonstrate that aniridia may be associated with metabolic abnormalities. Due to this study's small sample size and large variability in participants' ages, further studies with larger sample sizes and less participant age variability are recommended to explore the role of PAX6 in obesity and post-prandial GLP-1 release.