Understand and prevent the production of microbially-produced pro-diabetic metabolites in different ethnic groups: impact of protein dietary changes (MICRODIET)

The prevalence of obesity and type 2 diabetes (T2D) is increasing worldwide at
an allarming pace. A relatively new recognized player involved in the
pathophysiology of type 2 diabetes (T2D) is the gut microbiota .The gut
microbiota can be seen as an environmental factor that promotes
cardio-metabolic diseases (CMD) including diabetes, obesity and
atherosclerosis. The gut microbiota itself is strongly influenced by diet,
ethnicity and medication use.

Preleminary results has shown a diverse gut microbiota richness between
subjects from different ethnicities, with subjects of Surinamese/Caribbean
descens having the lowest gut microbiota diversity compared to Dutch
Caucasians. Other preleminary results from our group has identified the
Imidazole Propionate (ImP), a degredation product of the essential aminoacid
histidine, as a potential metabomolite which plays a role in
insulineresistance. We also found that the gut microbiota of T2D subjects drive
histidine degradation into ImP production and urocanate.

In the MICRODIET study we would like to investigate the effects of a short term
(3 months) high protein (HP) VS a low protein (LP) diet on gut microbiota
composition and production of pro-diabetic metabolites in T2D patients from
Caucasian and Carribean ethnicity.

We hypothesize that increased protein intake in T2D subjects will lead to an
increased production of pro-diabetic metabolites, such as ImP, and higher
plasma glucose levels. We also hypothesize that in some ethnic groups this
effect is larger due to a reduced microbial diversity

To investigate the effects of a short term (3 months) high protein (HP) diet
compared to a low protein (LP) diet in T2D patients of Caribbean and Caucasian
ethnic background with regards to gut microbiota composition and production of
pro-diabetic metabolites.

Furthermore, we will also investigate the oral microbiota compositation as this
is also linked with cardio-metabolic diseases (CMD), such as T2D.

This is a randomized controlled three months dietary intervention study
comparing the effects of a high vs low protein diet in T2D subjects of
Caucasian or Caribbean ethnicity.

Patients will be randomized to either a high protein or a low protein diet for
three months. They will have weekly contact with an AMC dietician and will also
record 3 day food diaries per week. Subjects are required to collect 24hours
urine and feces 3 times during the intervention.

The total duration of the study is three months and participants will visit the
AMC four times. All participants are required to fill out food diaries three
days per week and have weekly contact with the dietician. Subjects are required
to collect 24h urine and feces at baseline, week 6 and week 12 of the study.
Furthermore, subjects will undergo multiple blood sampling after a mixed meal
test (MMT). The proposed diet is safe and no immediate harm is likely to occur.
However, glycemic control of DM2 can theoretically worsen and we therefore
measure HbA1c again at 6 weeks. Subjects will be discontinued from the study if
HbA1c >9% (75mmol/mol). In total subjects will spent 5 hours in the AMC (2x 4h
for the MMT plus REE/BIA/questionnaires at baseline and 12 weeks, as well as 1
hour during time point 6 weeks) and we will collect 300ml blood (at baseline,
week 6 and week 12) in total.

The placing of the intravenous cannula in our study can be an unpleasant
experience for the subjects. There is a low risk of phlebitis at the
intravenous injection sites, this is unpleasant, but not harmful, of temporary
nature and self-limiting.

A potential benefit for participating in this study can be weight loss and with
that better glycemic control and reduced risk for major vascular events.
Futhermore, data from this project will increase our knowledge regarding the
production of pro-diabetic metabolites by the gut microbiota and potentially
give rise to new pathways which can be intervened.