Type 2 Diabetes Clinical Trial
Official title:
Effects of Processed Meat on Brain Regions Related to Reward and Craving in Patients With Type 2 Diabetes, Obese Subjects and Healthy Controls
The purpose of this study is to
1. Compare effects of two isocaloric meals (processed meat hamburger vs. vegetarian
sandwich) in response to the postprandial period by using functional brain imaging of
reward circuitry implicated in food motivation and energy balance in patients with type
2 diabetes (T2D), obese subjects and healthy controls.
2. Characterize some of the pathophysiological mechanisms of action of different meals in
obese and T2D subjects vs. in healthy controls (serum concentrations of glucose, FFA,
IRI, C-peptide, gastrointestinal hormones, oxidative stress markers)
The mesolimbic dopaminergic system of the brain, which converges on the nucleus accumbens
(part of the striatum), plays a central role in reward and craving, and this system appears
to mediate hedonic food responses. In rodent studies, extracellular concentrations of
dopamine and its metabolites in the nucleus accumbens increased more after the consumption of
highly palatable food than standard rodent feed pellets. Furthermore, microinjections of
opiate into the nucleus accumbens increased food intake and the reward value of food.
Clinical studies that used functional brain imaging have reported greater activation in the
nucleus accumbens or other regions of the striatum in obese than lean individuals after they
viewed or consumed palatable, high-calorie food. Of particular interest, striatal dopamine D2
receptor availability was significantly lower in obese individuals than in nonobese matched
controls, which raised the possibility that overeating may compensate for low dopaminergic
activity. The recurrent activation of the striatum may down-regulate dopamine availability
and further heighten the drive to overeat. However, the information on the exact effect of
different foods and nutrients on the mesolimbic dopaminergic system is missing.
Preliminary findings that lead to the project
A positive association between high consumption of total and red meat, especially processed
meat, and incidence of T2D has been demonstrated. Previous studies support the concept that
increased oxidative stress may play an important role in T2D manifestation. Dietary fat
quality has been proposed to be a critical factor. Several studies have suggested that a high
intake of saturated fatty acids naturally present in meat contributes to the risk of glucose
intolerance. In an intervention study, humans suffering from metabolic syndrome who were
consuming a diet rich in saturated fats displayed higher oxidative stress markers
postprandially. It is not clear if saturated fatty acids per se or via increased oxidative
stress markers may activate the mesolimbic dopaminergic system.
In contrast, some intervention trials (including ours) demonstrated a greater improvement in
insulin sensitivity, glycemic control and a reduction in oxidative stress markers in T2D
patients consuming a vegetarian diet compared to a conventional diabetic diet. The effect of
a vegetarian diet on the mesolimbic dopaminergic system has not been studied yet.
Aims and priorities of the project
The purpose of this study is to
1. Compare effects of two isocaloric meals (processed meat hamburger vs. vegetarian
sandwich) in response to the postprandial period by using functional brain imaging of
reward circuitry implicated in food motivation and energy balance in patients with type
2 diabetes (T2D), obese subjects and healthy controls.
2. Characterize some of the pathophysiological mechanisms of action of different meals in
obese and T2D subjects vs. in healthy controls (serum concentrations of glucose, FFA,
IRI, C-peptide, gastrointestinal hormones, oxidative stress markers)
Hypothesis
1. Obese and T2D subjects relative to lean healthy controls will show greater activation in
the gustatory cortex and in somatosensory regions in response to the intake of processed
meat hamburger (vs. a vegetarian sandwich). However, they will also show decreased
activation in the caudate nucleus in response to consumption of processed meat hamburger
(vs. a vegetarian sandwich).
2. Changes in serum concentrations of glucose, FFA, IRI, C-peptide, gastrointestinal
hormones and oxidative stress markers will be involved in gut-brain axis signaling. The
investigators hypothesise to find an association between postprandial changes in serum
concentrations of FFA and postprandial changes in activation in the gustatory cortex and
in somatosensory regions of the brain.
The actual need for this study The pandemic of obesity and diabetes especially in western
countries calls for high-quality research and relevant action. A better understanding of the
pathophysiological mechanisms of the stimulation of brain regions involved in reward and
craving in response to processed meat, one of the most significant present risk factors for
obesity and type 2 diabetes, is needed in order to develop more effective preventive and
therapeutic strategies.
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