Clinical trial NCT01297738: Diet, Insulin Sensitivity And the Brain
Official title: The Effect of Dietary Patterns and Diet Composition on Insulin Sensitivity and Cerebral Dopamine- and Serotonin Transporters
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Diabetes Mellitus Type 2
Keywords: diet manipulation
serotonin
dopamine
insulin sensitivity
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Netherlands Organisation for Scientific Research
First posted: 2011-02-17
Enrollment: 39
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief 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.

Eligibility criteria: Inclusion Criteria:

* BMI 19-26 kg/m2
* Age 18-40 years old
* Male gender
* Caucasian
* Stable weight 3 months prior to start study participation

Exclusion Criteria:

* Abnormal oral glucose tolerance test (OGTT)
* Lipid disorders, renal disorders, thyroid disorders, elevated liver enzymes
* Use of medication
* Use of alcohol \> 3/day
* Use of ecstasy, amphetamines or cocaine
* Smoking
* History of eating disorder or psychiatric disorder
* Any medical condition, intensive sports ( \>3 times/week), shift work

Primary outcomes:
measure: Cerebral binding of [123I]FP-CIT to serotonin- and dopamine transporters and correlation with changes in in vivo and ex vivo insulin sensitivity
timeFrame: At baseline and after 6 weeks of hypercaloric HFHS or HS diet
Secondary outcomes:
measure: Abdominal fat mass
timeFrame: At baseline and after 6 weeks of HFHS or HS hypercaloric diet
measure: Glucoregularoty hormones
timeFrame: At baseline and after 6 weeks of hypercaloric HFHS- or HS diet
measure: Insulin signalling pathways
timeFrame: At baseline and after 6 weeks of hypercaloric HFHS- or HS diet
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Mireille JM Serlie, Dr
role: STUDY_DIRECTOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Karin EM Koopman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koopman KE, Caan MW, Nederveen AJ, Pels A, Ackermans MT, Fliers E, la Fleur SE, Serlie MJ. Hypercaloric diets with increased meal frequency, but not meal size, increase intrahepatic triglycerides: a randomized controlled trial. Hepatology. 2014 Aug;60(2):545-53. doi: 10.1002/hep.27149. Epub 2014 May 13.