Central effects of endogenous GLP-1 and the GLP-1 analog liraglutide on brain satiety and reward circuits and feeding behavior in diabetes.
- Conditions
- obesitasadult onset diabetesdiabetes mellitus type 210018424
- Registration Number
- NL-OMON39550
- Lead Sponsor
- Vrije Universiteit Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 50
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 postload glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)
- 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 normal; fasting < 5.6 mmol/l and after OGTT t<=120min. < 7.8 mmol/l, impaired; fasting 5.7-7.1 mmol/l and after OGTT t<=120min 7.9-11.0 mmol/l)
- 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 fasting and 2h post load glucose as ascertained during a 75-g oral glucose tolerance test (OGTT)
- Right handed;For the obese individuals with T2DM:
- 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
- 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 gastroparese, 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 of allergy for acetaminophen.
- History of allergy for insulin analog
- History of allergy for liraglutide or other GLP-1 RA/analog
- 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
of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse,
parent, child, or sibling, whether biological or legally adopted.
- Individuals who have previously completed or withdrawn from this study or any other study investigating
GLP-1 receptor agonist or dipeptidyl peptidase (DPP)-4 within 6 months
- Left handed.
- Individuals who, in the opinion of the investigator, are unsuitable in any other way to participate in this
study.
- Individuals who are employed by NovoNordisk & comp. (that is, employees, temporary contract workers,
or designees responsible for conducting the study).
- Poor commandment of the Dutch language or any (mental) disorder that precludes full understanding
the purpose, instruction and hence participation in the study.
- Further exclusion criteria will be in compliance with the EMeA SPC of liraglutide.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>-The effects of endogenous GLP-1 in neuronal activity in CNS reward and satiety<br /><br>circuits (including striatum, amygdala, orbitofrontal cortex, insula,<br /><br>hypothalamus), as represented by BOLD fMRI signal change from baseline (%) in<br /><br>respons to food(-related) stimuli,<br /><br>- comparing the differences between obese T2DM patiernt and normoglycemic<br /><br>healthy, lean subject in this endogenous GLP-1 effect.<br /><br>- The involvement of the increased meal-related endogenous GLP-1 response after<br /><br>gastric bypass surgery in food-stimuli related neuronal activity in CNS reward<br /><br>and satiety circuits<br /><br>-The effects of GLP-1 analog treatment in T2DM patient on the CNS cirucuits<br /><br>described above.</p><br>
- Secondary Outcome Measures
Name Time Method