Diet, Insulin Sensitivity And the Brain (DISAB)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Status: Completed

Conditions: Diabetes Mellitus Type 2; Obesity

Treatments: Other: Meal size increase with HFHS; Other: Meal frequency increase with HFHS; Other: Meal frequency increase with HS; Other: Meal size increase with HS

Study type: Interventional

Funder types: Other

Identifiers

NCT01297738

DISAB

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: Male

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

39 participants in 5 patient groups

Meal size increase with HFHS

Experimental group

Description:

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®)

Treatment:

Other: Meal size increase with HFHS

Meal size increase with HS

Experimental group

Description:

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.

Treatment:

Other: Meal size increase with HS

Meal frequency increase with HFHS

Experimental group

Description:

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.

Treatment:

Other: Meal frequency increase with HFHS

Meal frequency increase with HS

Experimental group

Description:

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.

Treatment:

Other: Meal frequency increase with HS

Control group

No Intervention group

Description:

Subjects will not follow any diet but their own ad-libitum, healty diet.