Diet, Insulin Sensitivity And the Brain

Not Applicable

Completed

• Conditions: Obesity; Diabetes Mellitus Type 2
• Interventions: Other: Meal size increase with HFHS; Other: Meal size increase with HS; Other: Meal frequency increase with HFHS; Other: Meal frequency increase with HS

• Registration Number: NCT01297738
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-16
• Study First Submitted QC: 2011-02-16
• Study First Posted: 2011-02-17
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-23
• Last Update Posted: 2013-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 39

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Meal size increase with HFHS	Meal size increase with HFHS	On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a liquid meal which is high in fat and sugar (Nutridrink®)
Meal size increase with HS	Meal size increase with HS	On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming commercially available sugar-sweetened beverages. Subjects consume this caloric surplus with their meals, which results in an increase in meal size.
Meal frequency increase with HFHS	Meal frequency increase with HFHS	On top of a healthy, eucaloric diet, study subjects consume a 40% calory surplus by consuming a liquid meal which has a high fat and sugar content(Nutridrink®). Subjects consume the Nutridrink 3 times a day in between meals. which results in an increase in meal frequency.
Meal frequency increase with HS	Meal frequency increase with HS	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.

Primary Outcome Measures

Name	Time	Method
Cerebral binding of [123I]FP-CIT to serotonin- and dopamine transporters and correlation with changes in in vivo and ex vivo insulin sensitivity	At baseline and after 6 weeks of hypercaloric HFHS or HS diet	Difference in cerebral binding of the radioligand \[123I\]FP-CIT to serotonin- and dopamine transporters before and after dietary manipulations and correlation of cerebral dopamine and serotonin transporter binding with changes in in vivo and ex vivo insulin sensitivity.

Secondary Outcome Measures

Name	Time	Method
Abdominal fat mass	At baseline and after 6 weeks of HFHS or HS hypercaloric diet	Changes in accumulated amount of abdominal (visceral) and liver fat
Glucoregularoty hormones	At baseline and after 6 weeks of hypercaloric HFHS- or HS diet	Changes in glucoregulatory hormones such as glucagon and leptin
Insulin signalling pathways	At baseline and after 6 weeks of hypercaloric HFHS- or HS diet	Changes in insulin signalling pathways in peripheral fat and muscle tissue

Trial Locations

Locations (1)

Academic Medical Center; 🇳🇱 Amsterdam, Noord-Holland, Netherlands