Effects of caloric restriction and weight loss on hypothalamic function in response to glucose ingestion in patients with type 2 diabetes mellitus.

The hypothalamus plays a central role in the regulation of energy intake,
feeding behaviour and lipid and glucose metabolism. Previous functional
magnetic resonance imaging (fMRI) provided in vivo evidence for distinct
hypothalamic function in lean and obese humans. In obese subjects, the fMRI
signal in areas corresponding to the paraventricular and ventromedial nuclei in
response to glucose ingestion was attenuated and delayed. A recent study showed
that the hypothalamic response to glucose ingestion in patients with type 2
diabetes mellitus (DM2) is almost absent as compared to healthy individuals.
This may have important physiological sequelae, as the hypothalamus is
intimately involved in the control of glucose and lipid metabolism. Caloric
restriction and weight loss profoundly affect metabolic control in obese humans
with or without DM2.
To investigate whether caloric restriction and/or weight loss restore the
hypothalamic response to ingestion of glucose in patients with DM2, fMRI of
hypothalamic activity will be performed during ingestion of glucose solution in
patients with DM2 at three different time point during caloric restriction.

1) To determine the effects of caloric restriction on hypothalamic function in
response to glucose ingestion in patients with type 2 diabetes mellitus.

2) To determine the effects of weight loss on hypothalamic function in response
to glucose ingestion in patients with type 2 diabetes mellitus.

Experimental, longitudinal study, with within-individual comparison

Participants are on a low calorie diet for 6 weeks. During this period they
will undergo a fMRI examination that also comprises drinking of 300 ml glucose
solution.

Before inclusion, subjects will undergo a general medical exam, comprising
measurement of body length and weight, hip and waist circumference and body
composition by means of Bioelectrical Impedance Analysis (BIA). Also, 13 ml of
blood will be drawn for assessment of basement parameters

Subjects will visit the hospital on three occasions. Each visit takes two hours
and consists of a functional MRI examination of one hour and measurement of
body length and weight, hip and waist circumference and body composition (BIA).
During fMRI, subjects drink 300 ml of glucose solution, immediately before and
after fMRI 2 ml blood will be drawn.
Time will also be spent on evaluation of the diet program and coaching.

Participants treated with oral antidiabetic drugs are asked to stop this
medication 2 days prior to the baseline scan. All participants will be asked to
check fasting blood glucose daily and contact the supervising physician in case
the fasting blood glucose exceeds a value of 10 mmol/L. Participants will be
contacted on day 5, 10 and 21 of the diet for evaluation of fasting blood
glucose levels and for coaching. When fasting blood glucose remains below
threshold for more then 10 days, a specialist will be consulted to diminish
test frequency to once every two days.

Participants are on a low calorie diet for six weeks. Especially during the
first days, this may invoke lightheadeness or a general feeling of weekness.

Both the general medical examination at screening and the MRI images may yield
unexpected findings.