Metformin and Core Temperature in Obese and lean Males (McTOM)

Obesity and diabetes mellitus type 2 (DM2) are health problems with a
tremendous impact. Many attempts have been made to combat obesity and DM2,
however, a breakthrough therapy is still lacking.
Obesity is the result of an imbalance between energy intake and energy
expenditure. 18F-fluorodeoxy-d-glucose (18F-FDG) positron emission tomography
computed tomography (PET-CT) pinpoint areas with high glucose turnover.
Physiological 18F-FDG accumulation is frequently observed in the colon.
Therefore, the colon might play an important role in increasing energy
expenditure by consuming calories. However, the possibility of the colon as an
energy dissipating tissue has not yet been explored. The colon could become an
interesting new target of research to find a method to combat obesity.
Metformin is one of the few drugs in the treatment of DM2 that is associated
with moderate weight loss. Interestingly, patients using metformin show an
increased 18F-FDG-uptake in the colon. Whether this higher uptake of glucose
also cause an increase in core temperature and/or an increase in energy
expenditure is not known. The cause for this increase in glucose uptake in the
colon by metformin use is unknown. Also, it is unknown whether this increase in
glucose uptake results in an increased energy expenditure and/or an increase in
core body temperature.

In this study we aim to investigate the influence of metformin (500 mg 1/day)
on 18F-FDG uptake in the colon. We will also measure temperature in the colon
and energy expenditure in healthy lean (BMI <24 kg/m2) and obese subjects
(BMI>28 kg/m2).

In this non-randomised intervention study we will study the influence of
metformin (1000 mg/day (500 mg in the morning, 500 mg in the evening) during 1
week) on 18F-FDG uptake in the colon. The main outcome will be difference in
18F-FDG uptake. Furthermore, we will measure core body temperature, energy
expenditure and HOMA-index.
Visit 1. (screening) : Informed consent, evaluation of eligibility, medical
history, laboratory measurements.
Visit 2. : Weight, length, waist circumference, blood drawing, core body
temperature, EE, 18F-FDG PET CT. Start using metformin
Visit 3. : Weight, length, waist circumference, blood drawing, core body
temperature, EE, 18F-FDG PET CT.

Subjects will have to visit the AMC three times. Two times in a fasted state.
Furthermore, subjects will have to use metformin. Metformin is a widely used
drug with an established safety profile. The most-occurring side-effect is
gastrointestinal discomfort (diarrhoea, bloating, dyspepsia). This is mostly
seen at high doses and often ameliorates when using metformin for a longer
period. A rare but important complication is lactic acidosis. However, this is
most often seen in patients with either renal insufficiency or other underlying
causes of impaired lactate metabolism. Therefore, we only include healthy
subjects and kidney function will be checked before subjects start with the
metformin.
Also, we will use 18F-FDG PET-CT scans to evaluate the glucose uptake in the
intestine. The resulting dose from the two radioactive tracers + scans is 7.8
mSv.
The maximal dose for a participant during one year is 10 mSv. Nonetheless, we
will strongly emphasize that the participants will not participate in research
involving radiation in the two years following this study. Although the change
of developing cancer is minimal after participation in this study, we will only
include subjects aged over 40 years to minimalize the potential effect of
inducing cancer.
Last, the placing of the intravenous canulla in our study can be a unpleasant
experience for the subjects and there is a low risk of flebitis at the
intravenous injection sites.

Although the methods of our study are accompanied with a moderate risk for
healthy subjects, we find this to be justified with adding knowledge to finding
a solution for the major obesity and type 2 diabetes epidemic.