Defining the Physiological Mechanisms of Risk Genes for Hyperglycaemia, Insulin Resistance and Type 2 Diabetes
试验速览
- 阶段
- 不适用
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Calculated Incretin Effect
研究概览
简要总结
Recent genetic association studies have identified variants in the Peptidyl-Glycine alpha-amidating mono-oxygenase (PAM) gene that increase the risk of diabetes likely through a defect in beta-cell function. This has been followed up and supported by novel kinetic assays and cellular studies. This investigation will recall heterozygous carriers of the risk allele at rs78408340 and age, BMI and gender matched controls from the Oxford Biobank. The study will compare the incretin effect, glucagon-like peptide-1(GLP-1), insulin, glucose levels and PAM protein activity in individuals both with and without the risk variant. The aim of the study is to gain mechanistic insight into the effect of the variant on human physiology and diabetes pathogenesis.
详细描述
Note: The study will utilize an adaptive study design with an interim analysis at 40 volunteers (20 v 20) with the possibility of adding an additional 20 volunteers to the study (10 v 10) if the criteria for futility or clear effect are not met.
The criteria are; stop and reject null hypothesis if t > 2.490 and stop and accept null hypothesis if t < 1.033. If the t falls between these values an additional 20 volunteers (10 v10) will be recruited. The decision to stop or additional volunteers will be based on the incretin effect (primary outcome).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult, age 30-65 inclusive, healthy, appropriate genotype
- •Mental capacity to consent
排除标准
- •Demographics: <30 and >65 years old
- •Medical history: Bariatric surgery, surgery on gut/ stomach; history of recent significant weight loss (>10% of weight in last year); known cardiovascular disease
- •Medications: Currently prescribed glucose-lowering medication, oral/IV corticosteroid treatment, any medication effecting gastric motility or glucose metabolism
结局指标
主要结局
Calculated Incretin Effect
时间窗: 3 months
Will be calculated from the amount of IV glucose required to reproduce OGTT glycaemic profile
次要结局
- Insulin concentration(3 months)
- Glucose concentrations(3 months)
- GLP-1 (glucagon-like peptide-1) amidated and unamidated concentration(3 months)
- PAM enzyme activity assay(3 months)