Modulation of Protein Intake to Target Gut-microbiota Derived Metabolites of Amino Acids in Individuals With Type 2 Diabetes From Varying Ethnic Backgrounds
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 2
- 主要终点
- Post meal tolerance test glycemic excursion (area under the curve)
研究概览
简要总结
Context and justification:
There is growing evidence that the gut microbiota is a key element in the pathophysiology of cardio-metabolic diseases (CMD) such as Type 2 Diabetes (T2D). One hypothesis is that gut-derived metabolites (from diet) have an important role in the host metabolism. Preliminary results show that imidazole propionate (ImP), a degradation product of the essential amino acid histidine, is produced by the gut microbiota of T2D patients, but not healthy subjects. The gut microbiota itself is strongly influenced by diet and ethnicity. However, most dietary intervention studies have focused on the role of fiber intake and the effect of dietary protein on the gut microbiota composition and metabolite production is not well known. Our hypothesis is that, depending on the baseline gut microbiome composition, a diminution in protein intake could decrease the microbial production of metabolites such as ImP and improve the metabolism of the host. We also hypothesize that the effects of such an intervention could depend the ethnic background.
Objective:
To study the effects of a high protein (HP) vs a low protein (LP) diet on gut microbiota composition and production of pro-diabetic metabolites in type 2 diabetes (T2D) patients from Caucasian and Caribbean ethnicity depending on baseline metagenomics richness.
Study design:
Randomized controlled three months dietary intervention study
Study Population:
T2D patients from Caucasian (N=80) and Caribbean (N=40) background who are on a stable dose of metformin and do not use insulin or proton-pump inhibitors.
Intervention:
Subjects will be randomized to either a high protein (HP) or low protein (LP) diet for three months. Individuals of Caucasian ethnicity, will also be stratified according to either a high or low gut microbiota gene richness. All subjects will receive pre-cooked meals 6 days per week and daily food packages. Subjects are required to keep food diaries three days a week and will also have weekly contact with an Pitié-Salpêtrière dietician.
Outcome measures:
Primary endpoint is the change in glycemic excursion (area under the curve) after a mixed meal test between baseline and 12 weeks after the beginning of the intervention. Furthermore, we will study oral and fecal microbiota composition changes as well as serum levels of intestinal metabolites, such as ImP, body weight and body composition at baseline and after 12 weeks.
Sample Size:
It is calculated that a total of 20 patients per arm are needed so 120 patients in total.
详细描述
Context and justification:
There is growing evidence that the gut microbiota is a key element in the pathophysiology of cardio-metabolic diseases (CMD) such as Type 2 Diabetes (T2D). One hypothesis is that gut-derived metabolites (from diet) have an important role in the host metabolism. Preliminary results show that imidazole propionate (ImP), a degradation product of the essential amino acid histidine, is produced by the gut microbiota of T2D patients, but not healthy subjects. The gut microbiota itself is strongly influenced by diet and ethnicity. However, most dietary intervention studies have focused on the role of fiber intake and the effect of dietary protein on the gut microbiota composition and metabolite production is not well known. Moreover, it has been shown that the response to a dietary intervention may depend on the baseline gut microbiome richness.
Main hypothesis: Depending on the baseline gut microbiome composition, a diminution in protein intake could decrease the microbial production of metabolites such as ImP and improve the metabolism of the host. We also hypothesize that the effects of such an intervention could depend the ethnic background.
Study population:
Individuals with type 2 diabetes (T2D), of Caucasian or Caribbean origin, 120 patients will be included in total
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
- None
入排标准
- 年龄范围
- 40 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 40 years and <70 years
- •Type 2 Diabetic Subjects (T2D)
- •Treated with stable dose of metformin (no dose change in the last 3 months)
- •BMI ≥ 25 kg / m2
- •Caucasian or Caribbean origin
- •Written and oral comprehension of the French language
- •Patient affiliated to health care.
- •Patient having been informed of the study and having given written consent to participation
排除标准
- •Pregnancy or breastfeeding
- •Insulin treatment
- •HbA1c ≥ 9% (<3 months)
- •Recent antibiotic treatment (<3 months)
- •Recent treatment with proton pump inhibitor (<3 months)
- •Food allergies or documented intolerances
- •Patient not willing to eat the foods provided in the protocol
- •Neuromuscular or neurological disease
- •History of digestive cancer and / or abdominal radiotherapy
- •History of gastrointestinal surgery with gastrointestinal resection
- •Acute or chronic inflammatory or infectious disease (including HIV, HCV, HBV)
- •Organ Transplantation, Immunosuppressive drugs
- •Severe chronic renal insufficiency (creatinine> 150 μmol / l or eDFG <50 ml / min per 1.73 m2 body surface area)
- •Patient currently included in an interventional clinical study (patients included in an observational study may be included)
- •Patient who received an experimental treatment in a research involving the human person in the last 2 months
- •Subject taking a dietary supplement (> 100kcal / d)
- •Subject with severe eating disorders (anorexia, bulimia, binge eating disorders, etc.)
- •History of bariatric surgery
- •Subject practicing an intense sport activity (more than 10 hours of sport per week)
- •Subject unwilling to maintain an alcohol consumption of less than 50g per week (eg 5 glasses of wine) and less than 10g per day (eg 1 glass of wine)
- •Patient under tutorship or curatorship
结局指标
主要结局
Post meal tolerance test glycemic excursion (area under the curve)
时间窗: Change between baseline (T0) and the end of the intervention (T12 weeks)
After overnight fasting: Ingestion of 2x125ml de Fortimel® Compact (Nutricia) 600 kcal with 74g carbohydrates (50% of energy), 24g protein (16% of energy) et 23,2g fat (34% of energy). Blood glucose sampling à T0, 30, 60, 90, 120, 180, 240 min
次要结局
- Insulinogenic index (from post meal tolerance test glucose and insulin levels)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Fasting concentration of glucose(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of total cholesterol(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Serum concentration of glycated hemoglobin (HbA1c)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Insulin resistance index : HOMA 2 IR (based on fasting glucose and insulin concentration)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- One week postprandial glucose excursions measured by continuous glucose monitoring sensors (CGMS)(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- Fat free mass (BIA)(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- Concentration of HDL cholesterol(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Patient health questionnaire 9 score (PHQ-9 questionnaire)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Disposition index (kahn) (from post meal tolerance test glucose and insulin levels)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Sagittal diameter (cm)(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- Gastro-intestinal discomfort changes(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Fat mass (DXA)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Fat free mass (DXA)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Visceral fat mass (DXA)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of Trimethyl amine oxide (TMAO)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of C reactive protein (CRP)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Weight (kg)(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- Waist circumference (cm)(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- Resting energy expenditure changes(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Epigenetic modifications(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Adipose tissue gene expression modifications(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Fat mass (BIA)(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- Post meal tolerance test insulin excursion (area under the curve)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Matsuda index (from post meal tolerance test glucose and insulin levels)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Insulin secretion index: HOMA 2 B (based on fasting glucose and insulin concentration)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of triglycerides(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Gut microbiota changes(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Oral microbiota changes(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of p cresol(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Urinary urea excretion(Evolution between T0 (baseline) T6 weeks and T12 weeks of intervention)
- General self efficacy scale score (GSES questionnaire)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Fasting concentration of Alanine transaminase (ALT)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Fasting concentration of Aspartate transaminase (AST)(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of LDL cholesterol(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of Imidazole propionate(Change between baseline (T0) and the end of the intervention (T12 weeks))
- Concentration of indoxyl sulfate(Change between baseline (T0) and the end of the intervention (T12 weeks))
- SF 36 score (short form 36 quality of life questionnaire)(Change between baseline (T0) and the end of the intervention (T12 weeks))