The Interaction Between Protein Intake, Gut Microbiota and Type 2 Diabetes in Subjects With Different Ethnic Backgrounds

NCT03732690 | Completed

• 2 other identifiers: P180402J2018-A01606-49
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes

Keywords

Type 2 diabetes; Diet; Protein; Gut microbiota; Metabolites

Outcome Measures

Primary Outcomes (1)

• Post meal tolerance test glycemic excursion (area under the curve)

  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

  Change between baseline (T0) and the end of the intervention (T12 weeks)

Secondary Outcomes (38)

• 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)

• Insulinogenic index (from post meal tolerance test glucose and insulin levels)

  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)

• Serum concentration of glycated hemoglobin (HbA1c)

  Change between baseline (T0) and the end of the intervention (T12 weeks)

Study Arms (2)

Diet High Protein (HP)

OTHER

Diet High Protein (HP) : 30% protein, 40% carbohydrate and 30% fat

Other: Diet HP

Diet Low Protein (LP)

OTHER

Diet Low Protein (LP) : 10% protein, 55% carbohydrate and 35% fat

Other: Diet LP

Interventions

Diet HP OTHER

2000kcal for men 1800 kcal for women. Food boxes (HP pre-cooked meals and meat/chicken/fish portions, HP breads and snacks) will be provided to the participants throughout the study reaching 40-50% of their prescribed daily energy intake for 6 days per week. In total 932 kcal are provided through this food boxes (54g of carbohydrate, 101g of protein, 34,6g of fat). The rest of the daily food intake will be guided by a dietician with a list of recommended high protein foods. Subjects are required to keep food diaries three days a week and will also have weekly contact with a dietician.

Diet High Protein (HP)

Diet LP OTHER

2000kcal for men 1800 kcal for women. Food boxes (LP pre-cooked meals, LP breads and snacks) will be provided to the participants throughout the study

Diet Low Protein (LP)

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 40 years and \<70 years 2.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• ICAN Nutrition Education and Research: collaborator

Study Sites (1)

Hôpital PITIE SALPETRIERE - APHP

Paris, 75013, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Karine CLEMENT

  Hôpital PITIE SALPETRIERE - APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: November 7, 2018
• Study Start: December 5, 2018
• Primary Completion: April 14, 2021
• Study Completion: April 14, 2021
• Last Updated: September 10, 2021

Record last verified: 2021-09

Locations

FR (1)