Evaluation of the Enteroinsular Axis in Cystic Fibrosis
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 550
- 试验地点
- 4
- 主要终点
- Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes.
研究概览
简要总结
Cystic fibrosis related diabetes (CFRD) is associated with worse CF-relevant outcomes.
The mechanisms underlying CFRD development are not fully understood, but recent evidence suggests Type 2 Diabetes Mellitus (T2DM) mechanisms may be involved and may involve incretins (gut secreted hormones that augment insulin secretion in response to a nutrient load).
This study will examine the prevalence of Genome wide association study (GWAS)-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in CF and will use this information to compare incretin and insulin secretion in non-diabetic children and adults with high risk and low risk alleles.
详细描述
CFRD is associated with worse nutritional status, greater pulmonary function decline, and increased mortality, highlighting its relevance in CF and arises primarily from compromised insulin secretion--traditionally considered a by-product of pancreatic exocrine tissue damage and fibrosis. Recent developments in the field of diabetes are propelling a re-examination of this basic explanation. Genome-wide association studies have associated genetic variants in TCF7L2, a transcription factor implicated in enteroendocrine function, with increased susceptibility to T2DM and CFRD.
The Objectives of this study are to perform targeted sequencing of TCF7L2 and other GWAS-associated T2DM genes in the pediatric and adult CF populations and then to compare insulin secretory capacity, β-cell sensitivity to glucose, and incretin secretion in non-diabetic CF subjects with high and low-risk alleles.
Phase 1 will include 450-500 subjects (Children age>= 2 years, adolescents, and adults) for TCF7L2 genotype and ten other GWAS-implicated T2DM genes. The distribution of TCF7L2 and other GWAS-implicated T2 DM genes across the spectrum of glucose abnormalities will be described. Phase 1 requires a single blood or saliva sample and review of medical records.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects age >2y
- •Diagnosis of Cystic Fibrosis
- •For subjects< 18 years, parental/guardian permission (informed consent) and if appropriate, child assent
排除标准
- •Established diagnosis of non-CFRD (cystic fibrosis related diabetes) (e.g T1DM)
研究组 & 干预措施
Patients with Cystic Fibrosis
Blood or saliva sample collection and medical record review.
干预措施: Blood or Saliva Sample Collection (Genetic)
结局指标
主要结局
Blood sample for DNA to genotype TCF7L2 and about 10 other GWAS-implicated T2DM genes.
时间窗: 1 day
To examine the prevalence of GWAS-implicated T2DM alleles (including TCF7L2) across the spectrum of glucose abnormalities in children and adults with CF.
次要结局
未报告次要终点