Is the Gut Microbiome Associated With Residual Β-Cell Function and DeVElopment of Complications in Individuals With Longstanding Type 1 Diabetes Mellitus (MARVEL)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 5,000
- 主要终点
- Residual β-cell insulin secretion capacity:
研究概览
简要总结
This study looks at whether people with type 1 diabetes have different gut bacteria. We also want to see if this is linked to keeping insulin production up and preventing complications like heart disease and nerve damage. The aim is to find ways to keep more of the functions working, avoid low blood sugar and reduce diabetes complications.
详细描述
Rationale: It has become apparent that most individuals with type 1 diabetes mellitus (T1D) have some remaining β-cell function. Individuals with T1D and a preserved β-cell function have a lower risk of hypoglycemia and diabetic complications. The factors regulating residual β-cell function are unknown. A likely mechanism leading to β-cell preservation is regulation of immunological tone by the gut microbiome. Recently we published in a small pilot cohort (GUTDM1, METC 2020_105) that residual β-cell function is linked to better glycemic control (time in range) and linked to specific gut microbiota composition. Since this cohort was too small to also show a link with presence of diabetic complications and recruit enough individuals with preserved β-cell function for confirmatory intervention trials to increase β-cell function, we will now aim to recruit a larger follow-up cohort. The aim of this cohort is to a) investigate whether residual β-cell function is associated with gut microbiome composition and circulating immune cell counts in individuals with T1D and diabetic complications b) identify 500 potential eligible individuals with preserved β-cell function for future intervention trials.
Objective:
- To investigate whether T1D individuals with preserved β-cell function exhibit a distinct gut microbial and circulating immune cell signature, leading to a reduced incidence of diabetes complications (CVD, nephropathy, neuropathy, and retinopathy).
- Identify individuals with preserved β-cell function for diagnostics as well as future intervention studies to increase β-cell function.
Study design: 10-year longitudinal observational multicenter cohort study
Study population: 5000 individuals with type 1 diabetes >18 years of age, visiting the outpatient clinic of Diabeter center Amsterdam and Diabeter Nederland.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All individuals with T1D visiting the outpatient clinic of Diabeter Center Amsterdam or Diabeter Nederland are potentially eligible if they are >18 years old.
- •T1D diagnosis is made by the primary clinician prior to the study visit. Presence of auto- antibodies at time of diagnosis will be recorded.
排除标准
- •Active infection during the study visit
- •Inability or unwillingness to donate feces or urine.
- •Smoking or illicit drug use (e.g. MDMA/amphetamine/cocaine/heroin/GHB) in the past three months or use during the study period.
- •Inability or unwillingness to provide informed consent.
- •Absence of a large bowel (ie colostomy)
结局指标
主要结局
Residual β-cell insulin secretion capacity:
时间窗: At 0,3,6 and 10 years follow-up.
assessed by non-invasive 2-hour post meal c-peptide release (residual β-cell function) in urine, composed of a urinary c-peptide to creatinine ratio (UCPCR).
次要结局
- Glycemic control:(At 0,3,6 and 10 years follow-up.)
- Presence and incidence of diabetes complications(At 0, 3, 6 and 10 years follow up)
- Intestinal microbiota composition(At 0,3,6 and 10 years follow-up.)
研究者
Max Nieuwdorp
prof dr
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)