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

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

Interventions

OTHER

Diet HP

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.

OTHER

Diet LP

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

Sponsors & Collaborators

• ICAN Nutrition Education and Research

  collaborator INDUSTRY

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Karine CLEMENT · Hôpital PITIE SALPETRIERE - APHP

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

40 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-12-05

Primary Completion

2021-04-14

Completion

2021-04-14

Countries

• France

Study Locations