MicrobiAr: Characterization and Follow-up of Microbiome and Health Indicators in Obese, Pre-Diabetes and Type 2 Diabetes Cohorts Undergoing a Plant-based Diet and Lifestyle Intervention
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 发起方
- 入组人数
- 468
- 试验地点
- 1
- 主要终点
- Clinical improvements in people with type 2 diabetes, prediabetes, or obesity
研究概览
简要总结
The incidence of type 2 diabetes worldwide is growing rapidly, being one of the fastest growing global health emergencies of the 21st century according to the International Diabetes Federation. In MicrobiAr the investigators seek to achieve type 2 diabetes remission through a plant-based diet and lifestyle intervention identifying and characterizing key changes on the gut microbiome during clinical transitions. Specifically, the investigators aim to characterize and follow-up metabolic pathways from gut microbiome and how they evolve as long as health indicators do over the 2 years of this study.
详细描述
The present study has 2 stages, one cross-sectional and the other longitudinal. In the cross-sectional stage, a characterization of a single sampling of 480 people divided into 4 cohorts of 120 people each will be carried out: reference controls, subjects with obesity, with prediabetes and with type 2 diabetes. A clinical history will be made, as long as a 7-day food record and clinical laboratory tests. Anthropometric assessment will be carried out by recording weight, height, waist and hip circumference, determination of waist/hip ratios, as well as taking 4 skinfolds, bicipital, triceps, subscapular and suprailiac, arm and calf measurements and force through a dynamometer. The 480 people will also undergo gut microbiota and microbiome tests from stool samples.
During the longitudinal stage, subjects of each cohort (120 with obesity, 120 with prediabetes and 120 with type 2 diabetes) will be randomly divided into two intervention groups (with 60 subjects each). One group will follow a non-intensive intervention (personalized face-to-face follow-up every 2 months). The other group will follow an intensive intervention (personalized face-to-face follow-up every 3 weeks and a weekly remote group meeting). In both cases, a food plan will be followed based on the recommendations of the nutrition service of the Hospital de Clínicas, Argentina, in accordance with recommendations from the American Diabetes Association (ADA) 2019 guidelines with an emphasis on plant-based diet and whole foods.
Follow-up and nutritional guidance
Groups of 15 subjects from each intervention arm will be led by 3 healthcare professionals. In every case, the group's functions will be:
- Obtain a unique 7 day food-recall from all subjects, and upload the data to "MAR24" platform (for the transversal stage).
- Obtain a 2 day food-recall (including one day from the weekend) from all subjects every two months, and upload the data to "MAR24" platform (for the longitudinal stage).
- Complete a shared spreadsheet with clinical, biochemical and anthropometric parameters of every subject's visits to the hospital.
- Collaborate in Whatsapp unidirectional groups. In the non-intensive arm, the messages will only be to remember patients about their visits to the hospital, while in the intensive arm it will also be about other activities, such as workshops.
- Detect subjects who miss their appointments, to establish personalized contact and apply motivational strategies in order to reduce dropout risk.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for control or reference group:
- •Subjects without type 2 diabetes, obesity, prediabetes (glucose intolerance), or metabolic syndrome
- •HbA1c less than 42mmol/mol (<5.7%)
- •BMI between 18.5 and 24.9
- •Inclusion Criteria for people with obesity:
- •BMI greater than 30
- •Inclusion Criteria for people with prediabetes:
- •Fasting glucose between 110 and 125 mg/dl
- •HbA1c between 42 and 47 mmol/mol (5.7% to 6.4%)
- •BMI greater than 30
- •Inclusion Criteria for people with type 2 diabetes:
- •Fasting glucose > 126 mg/dl
- •HbA1c > 48mmol/mol (6.5% or higher)
- •BMI greater than 30
- •Treatment with metformin at therapeutic dose (1500-2000 mg/day) or maximum tolerated dose.
排除标准
- •Subjects with obesity, pre-diabetes medicated with metformin or another drug for diabetes or obesity
- •Subjects with type 2 diabetes medicated with another drug that is not metformin
- •Subjects with type 2 diabetes diagnosed over 6 years
- •Subjects with type 2 diabetes requiring insulin
- •Chronic kidney disease grade greater than 3 (measured by EPI)
- •Subjects with type 1 diabetes
- •Intestinal diseases, Crohn's, ulcerative colitis, celiac disease
- •Use of antibiotics in the last 3 months
- •Pregnancy, lactation
- •Psychiatric disorders
- •Eating disorder
- •Gastric bypass surgery
- •Transplanted people
- •Oncological pathology diagnosed less than 5 years
- •Subjects who do not wish to sign the informed consent
- •Subjects who do not agree to participate in the study over the 2 years follow-up
- •Subjects who do not have electronic devices and the internet to hold virtual meetings
研究组 & 干预措施
Reference Group
People between 30-60 years old, without obesity, prediabetes or type 2 diabetes.
The purpose of this group is to characterize gut microbiota and microbiome to set the reference values of the argentinian local population.
Obesity Group A
People between 30-60 years old, diagnosed with obesity assigned to the non-intensive intervention.
干预措施: Non-intensive intervention (Behavioral)
Obesity Group B
People between 30-60 years old, diagnosed with obesity assigned to the intensive intervention.
干预措施: Intensive intervention (Behavioral)
Prediabetes Group A
People between 30-60 years old, diagnosed with prediabetes assigned to the non-intensive intervention.
干预措施: Non-intensive intervention (Behavioral)
Prediabetes Group B
People between 30-60 years old, diagnosed with prediabetes assigned to the intensive intervention.
干预措施: Intensive intervention (Behavioral)
Type 2 Diabetes Group A
People between 30-60 years old, diagnosed with type 2 diabetes assigned to the non-intensive intervention.
干预措施: Non-intensive intervention (Behavioral)
Type 2 Diabetes Group B
People between 30-60 years old, diagnosed with type 2 diabetes assigned to the intensive intervention.
干预措施: Intensive intervention (Behavioral)
结局指标
主要结局
Clinical improvements in people with type 2 diabetes, prediabetes, or obesity
时间窗: at 2 years, checked every 6 months
These clinical improvements will be defined as: 1. In the group of subjects with type 2 diabetes, remission to non-diabetic stage. Considering remission as measuring HbA1c values lower than 6,5% at least 6 months after beginning the lifestyle intervention and 3 months after cessation of any pharmacotherapy, according to the "Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes", Diabetes Care 2021;44(10):2438-2444. 2. In the group of subjects with prediabetes, remission to normal glycemia / HbA1c values. Considering normal glycemia lower than 100 mg/gl and HbA1c lower than 5.7%. 3. In the group of overweight-obese subjects, a 10% decrease in weight compared to baseline weight, maintained during the second year of follow-up. Any of the three possible situations will be considered as a clinical improvement event.
Gut microbiota metabolic pathways changes
时间窗: at 2 years, checked every 6 months
Increase in the number of gut microbiota metabolic pathways possibly expressed in subjects of intensive intervention compared to their baseline states and also compared to subjects of the non-intensive intervention. This metric refers to possibly expressed metabolic pathways predicted from shotgun metagenomics analysis related to regulation of inflammatory processes, carcinogenesis, intestinal barrier function, oxidative stress, production of SCFAs, regulation of immune response and inflammation, production of derivative aromatic amino acids, regulation of bile acids (synthesis of derivative metabolites of cholesterol), regulation of the level of phospholipid synthesis (anaerobic metabolism of choline).
次要结局
- Insulin resistance(at 2 years)
- Gut microbiota diversity changes(at 2 years, checked every 6 months)
- Metabolic syndrome regression(at 2 years, checked every 6 months)
研究者
Juan Pablo Bustamante
Bioinformatician, PhD in Biological Chemistry
National Council of Scientific and Technical Research, Argentina