Diet, Insulin Sensitivity And the Brain
Condition: Obesity; Diabetes Mellitus Type 2
MeSH terms: Insulin Resistance; Diabetes Mellitus, Type 2; Hypersensitivity
Study type: Interventional

Summary: 
      Obesity and insulin resistance may be in part explained by an altered reward system with
      changes in the serotonin/dopamine system. These changes might be caused by changes in dietary
      habits, especially by an increased intake of liquid sugar and an increase in meal frequency.
      The investigators hypothesize that increasing meal frequency compared to increasing meal size
      and when consuming a hypercaloric high-sugar diet (HS) compared to a hypercaloric
      high-fat-high-sugar diet (HFHS) will result in a reduction in cerebral serotonin and dopamine
      transporters and in a more prominent increase in insulin resistance. In addition, the
      investigators hypothesize that the changes in insulin sensitivity will be independent of
      changes in abdominal (visceral) and liver fat and that changes in insulin sensitivity due to
      the dietary manipulation will co-occur with changes in insulin signaling pathways in
      peripheral fat and muscle tissue.
    

Detailed description: 
      Lean, healthy, young men will follow a hypercaloric HF- or HFHS diet for 6 weeks. Before and
      after the dietary intervention, the investigators will perform a SPECT-scan for serotonin and
      dopamine transporters with the radioligand [123I]FP-CIT, administered intravenously. The
      investigators will also perform a structural MRI for localization. Furthermore the
      investigators will perform a liver MRS and abdominal MRI for liver fat- and abdominal
      visceral fat measurement. The investigators will also perform a euglycemic, hyperinsulinemic
      clamp to measure insulin sensitivity and muscle- and fat biopsies to examine changes in
      insulin signaling pathways and fat metabolism. After the hypercaloric diet subjects will
      follow a hypocaloric diet until their weight is back to baseline.
    

Intervention name(s): Meal size increase with HFHS; Meal size increase with HS; Meal frequency increase with HFHS; Meal frequency increase with HS
Intervention type(s): Other; Other; Other; Other
Intervention description(s): On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® with their meals, which results in an increase in meal size.; On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages with their meals, which results in an increase in meal size.; On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a high-fat, high-sugar liquid medical food supplement (Nutridrink®). Subjects consume the Nutridrink® 3 times a day in between meals, which results in an increase in meal frequency.; On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume these sugar-sweetened beverages 3 times a day in between meals, which results in an increase in meal frequency.
Other intervention name(s): Nutridrink; Nutridrink
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: diet manipulation; serotonin; dopamine; insulin sensitivity