Insulin Resistance, Obesity, Morbid
Conditions
Keywords
obesity, insulin resistance, central nervous system inflammation, bariatric surgery
Brief summary
Background: Morbid obesity is associated with decreased brain µ-opioid receptor availability, possibly resulting in higher food intake needed to gain pleasure from eating. This decrease seems to normalize already 6 months after bariatric surgery, but the longer-term effects have not been studied. Obesity and insulin resistance result in significantly increased brain insulin-stimulated glucose uptake, whereas in every other tissue glucose uptake is lower. One possible explanation to this could be central inflammation and activation of brain glial cells, which has been shown to occur in animal models of obesity. Obesity has also been shown to associate with increased risk of Alzheimer's disease and cognitive decline in several studies. Aims: The first objective of this study is to both study the effects of bariatric surgery as well as compare the effects of gastric bypass and sleeve gastrectomy on food-associated pleasure, extending the follow-up period to 2 years postoperatively. The second aim is to investigate the effect of morbid obesity and weight loss on brain inflammation and gliosis and its association with increased brain insulin-stimulated glucose uptake. Furthermore, association of obesity, insulin resistance, central inflammation and neurocognitive dysfunction are evaluated.
Detailed description
Methods: A total of 60 morbidly obese subjects, 30 assigned for Roux-en-Y gastric bypass and 30 for sleeve gastrectomy according to routine treatment protocols will be recruited for this study. A control group of 30 healthy subjects will also be recruited. We will perform 1) structural MRI and MRS, 2) functional MRI during tasting and visual food cues, 3) PET imaging of µ-opioid receptor availability using \[11C\]-carfentanil, 4) PET imaging of cerebral inflammation and astrocyte activation using \[11C\]-PK11195, 5) measurement of whole-body and tissue insulin sensitivity by combining hyperinsulinemic, euglycemic clamp with \[18F\]-FDG-PET, 6) neuropsychological testing. The control group will only be studied once, whereas study procedures will be repeated for the morbidly obese before very-low calorie diet and 6, 12 and 24 months postoperatively.
Interventions
PROCEDUREBariatric surgery
Roux-en-Y gastric bypass or sleeve gastrectomy, chosen based on routine evaluation process
Sponsors
Turku University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
60 subjects undergoing bariatric surgery (either Roux-en-Y gastric bypass or Sleeve gastrectomy) and 30 healthy controls
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Morbidly obese group 1. BMI 35.0-45.0 kg/m2, or BMI 32.0-45.0 kg/m2 and diagnosed diabetes 2. Age 18-60 years 3. Eligible to bariatric surgery evaluated according to normal treatment paradigm Non-obese controls 1. BMI 18-27 kg/m2 2. Age 18-60 years 3. Fasting plasma glucose ≤6.1 mmol/L 4. Normal values in 2-hour oral glucose tolerance test
Exclusion criteria
Morbidly obese group 1. Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, braces, foreign fragments) 2. Previous participation in PET studies 3. Pregnancy 4. Poor compliance, alcohol or drug abuse 5. Weight over 150 kg or waist circumference over 150 cm 6. Diabetes with fasting glucose levels ≥7.0 mmol/L, or treatment with insulin 7. Any chronic disease, medication or condition that could create a hazard to subject safety, endanger study procedures or interfere with the interpretation of results. Non-obese controls 1. Metal objects in the body (including pacemakers, metallic artificial valve prostheses, inner ear implants, surgical clipses, braces, foreign fragments) 2. Previous participation in PET studies 3. Pregnancy 4. Poor compliance, alcohol or drug abuse 5. Smoking 6. History of eating disorders, drastic weight-gain or weight-loss 7. History of psychiatric disorders 8. Any chronic disease, medication or condition that could create a hazard to subject safety, endanger study procedures or interfere with the interpretation of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in central inflammation | Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively | Assessment of brain glial cell activation using \[11C\]-PK11195 tracer and positron emission tomography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in central reward system using fMRI imaging | Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively | Assessment of brain reward system activation after visual/taste cues using functional MRI |
| Changes in brain μ-opioid receptor availability using PET imaging | Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months postoperatively | Assessment of brain μ-opioid receptor availability using \[11C\]-carfentanil tracer and positron emission tomography |
| Changes in cognitive function studied with testing | Controls: 0 months; Morbidly obese: preoperatively, 6 months, 12 months, 24 months postoperatively | Neuropsychological testing focusing on memory, decision-making and inhibition |
| Changes in whole-body insulin sensitivity usign FDG-PET imaging | Controls: 0 months; Morbidly obese: preoperatively, 6 months postoperatively | Assessment of whole-body insulin sensitivity using hyperinsulinemic, euglycemic clamp |
| Changes in tissue-specific insulin sensitivity using FDG-PET imaging | Controls: 0 months; Morbidly obese: preoperatively | Assessment of insulin-stimulated glucose uptake in the brain, liver, skeletal muscle and adipose tissue by performing positron emission tomography with \[18F\]-fluorodeoxyglucose tracer during hyperinsulinemic, euglycemic clamp |
Countries
Finland
Outcome results
None listed