Processed Meat and Brain Regions Related to Reward and Addiction
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      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)
    

Detailed description: 
      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.
    

Intervention name(s): Processed meat hamburger; Vegan sandwich
Intervention type(s): Other; Other
Intervention description(s): MacMuffin Fresh 300 ml Cafe Latte + 21 g sugar Energy: 513.6 kcal Carbohydrates 55g (44.8%) Proteins 20.5g (16.7%) Lipids 22 g (38.6%); Burger with tofu + 300 ml green tea Energy 514.9 kcal Carbohydrates 54.2 g (44%) Proteins 19.9 g (16.2%) Lipids 22.8 g (39.8%)
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic