Effects of Glucagon Like Peptide-1(GLP-1) and Liraglutide on Brain Satiety and Reward Circuits and Feeding Behavior in Diabetes

• Status: Completed
• Trial end date: 2015-01-01
• Target enrollment: 0
• Participant gender: All

Summary

The aim of this study is to investigate if endogenous Glucagon Like Peptide -1 (GLP-1) has an effect on brain satiety and reward systems and if there are alterations in obese patients with type 2 diabetes (T2DM). Secondly, the aim is to investigate whether treatment with a GLP-1 analog, liraglutide, restores these signals in obese patients with type 2 diabetes. Finally, also the endogenous GLP-1 effects will be investigated in obese individuals before and after gastric bypass surgery on brain satiety and reward systems.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: VU University Medical Center
• Treatments: Glucagon; Glucagon-Like Peptide 1; Insulin; Insulin Glargine; Insulin, Globin Zinc; Liraglutide

Criteria

Inclusion Criteria:

• For the healthy, lean individuals:

• Age 18-65 years

• Women: post menopausal (excluding possible menstruation cycle effects)

• Body-mass index (BMI) of <25 kg/m2,

• Stable bodyweight (<5% reported change during the previous 3 months).

• Normal fasting and 2h post load glucose as ascertained during a 75-g oral glucose tolerance test (OGTT) (34)

• Right handed

For the obese T2DM individuals:

• Age 18-65 years

• Women: post menopausal (excluding possible menstruation cycle effects)

• BMI 25-40 kg/m2

• Stable bodyweight (<5% reported change during the previous 3 months).

• Diagnosed with T2DM > 3 months prior to screening

• HbA1C 6.5-8.5%

• Treatment with metformin at a stable dose for at least 3 months.

• Right handed

For the obese individuals scheduled for gastric bypass surgery:

• Age 18-65 years

• Women: preferably post menopausal (excluding possible menstruation cycle effects)

• Body-mass index (BMI) of >30 kg/m2,

• Stable bodyweight (<5% reported change during the previous 1 months).

• Normal or impaired fasting and 2h post load glucose as ascertained during a 75-g oral glucose tolerance test (OGTT) (defined as glucose fasting < 7.1 mmol/l and after OGTT t=120min < 11.0 mmol/l) (39)

• Right handed

Exclusion Criteria:

• GLP-1 based therapies, thiazolidinediones, sulphonylurea or insulin within 3 months before screening

• Weight-lowering agents within 3 months before screening.

• Congestive heart failure (NYHA II-IV)

• Chronic renal failure (glomerular filtration rate < 60 mL/min/1.73m2 per Modification of Diet in Renal Disease (MDRD))

• Liver disease

• History of gastrointestinal disorders (including gastropareses, pancreatitis and cholelithiasis)

• Neurological illness

• Malignancy

• Other type of bariatric surgery (Redo-GBP, sleeve, distal GBP, adj banding, Scopinaro)

• History of major heart disease

• History of major renal disease

• Pregnancy or breast feeding

• Implantable devices

• Substance abuse

• Addiction

• Contra-indication for MRI, such as claustrophobia or pacemaker

• Any psychiatric illness; including eating disorders and depression

• Chronic use of centrally acting agents or glucocorticoids within 2 weeks immediately prior to screening.

• Use of cytostatic or immune modulatory agents

• History or known allergy for acetaminophen.

• History of allergy for insulin analog

• History of allergy for liraglutide

• Participation in other studies

• Individuals who have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry

• Individuals who are investigator site personnel, directly affiliated with the study, or are immediate family