Functional magnetic resonance imaging of human hypothalamic responses to oral glucose ingestion in obese and lean subjects

Recently, a simple and robust method has been developed to determine
differences in homeostatic response, during food-intake by measuring the state
of activation of the hypothalamus using functional magnetic resonance imaging
(fMRI) .

Functional magnetic resonance imaging (fMRI) is a non-invasive method, which
detects transient haemodynamic changes in the brain, based on blood oxygen
level dependent (BOLD) signal differences in response to external or internal
stimuli. BOLD signal differences (contrasts) measured with T2* weighted fMRI
imaging sequences are dependent on local and global oxygen content, blood
volume, perfusion and tissue metabolism. These factors potentially influence
the oxy-to-deoxyhemoglobin ratio, and hence result in variation in the fMRI
signal. Measuring hypothalamic activity to oral glucose load using fMRI, has
been shown to be feasible in several studies. A well-defined and validated
protocol for the scan itself and for the data processing is therefore
available.

In recent studies we have demonstrated attenuated hypothalamic response to
glucose ingestion in diabetic subjects and reversal of this phenomenon when
diabetic subjects are subjected to a short-term stringent diet. We hypothesize
that insulin resistance is the key factor driving this principle. To further
elucidate this principle we want to compare non-diabetic obese subjects to lean
subjects. Non-diabetic obese subjects in general have insulin resistance, but
do not have high glucose levels, making them a good subjects to further
elucidate this matter.

Further understanding of the mechanisms driving altered hypothalamic signaling
in diabetic and obese people could help develop new treatment strategies for
obese pre-diabetic subjects to prevent progression to diabetes.

We hypothesize that non-diabetic obese subjects will demonstrate an attenuated
hypothalamic response to glucose ingestion, comparable to the diabetic subjects
we described earlier.

Therefore we will perform a case-control study in non-diabetic obese and lean
subjects, investigating their hypothalamic response to glucose ingestion.

The objective of the study is to determine hypothalamic function in response to
oral glucose ingestion in obese subjects.

The study will be a randomized cross-over observational study, consisting of
two study occasions. The occasions consist of ingestion of either glucose or
water.

There is a minimal burden/risk for the subjects. They have to attent sober on
scandays, but will be scanned early in the morning. They will receive a
intravenous catheter twice for a short period of time. The intake of
glucosewater can cause mild nausea. The accumalative time spend in the hospital
is two hours.