Effect of Weight Loss on Brain Insulin Sensitivity in Humans

Study Overview
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Brief Summary
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Obesity if known to be associated with brain insulin resistance in humans. This condition has not only implication for the brain but also for whole-body energy homeostasis. Research in rodents indicates that weight loss is able to improve insulin sensitivity of the brain. The current project will test this hypothesis in humans. Therefore, brain insulin sensitivity will be assessed by fMRI in combination with intranasal insulin administration, using an established protocol. Furthermore, effects of daily administration of insulin nasal spray (versus placebo) over 8 weeks will be assessed as secondary (exploratory) variables.

Official Title
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Effekt Von Gewichtsabnahme Auf Die zentralnervöse Insulinresistenz Des Menschen

Conditions
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Insulin Resistance

Intervention / Treatment
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* Other: nasal insulin
* Other: placebo spray


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HbA1c <6.5% Age between 40 and 75 years No intake of antidiabetic drugs or drugs for weight reduction no steroid intake Stable medication over 10 weeks before the start of the study Exclusion Criteria: Persons who wear non-removable metal parts in or on the body. Persons with reduced temperature sensitivity and / or increased sensitivity to heating of the body Cardiovascular disease can not be ruled out, e.g. manifest coronary heart disease, heart failure greater than NYHA 2, previous heart attack, stroke condition Persons with hearing impairment or increased sensitivity to loud noises People with claustrophobia Minors or non-consenting subjects are also excluded Subjects with an operation less than 3 months Simultaneous participation in other studies Neurological and psychiatric disorders Subjects with hemoglobin Hb <11 g / dl Hypersensitivity to any of the substances used

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: nasal insulin<br>daily administration of 160 U of human insulin as nasal spray | Other: nasal insulin<br> <br> |
| Placebo Comparator: placebo spray<br>daily administration of placebo solution as nasal spray | Other: placebo spray<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| brain insulin sensitivity | fMRI measurement will be performed before and after administration of 160 U of human insulin as nasal spray. Changes in regional activity will be quantified to assess regional brain insulin sensitivity. | 30 minutes after administration of nasal insulin | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body weight. | Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body weight will be recorded. | 8 weeks | 
| Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on glucose tolerance . | Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks glucose tolerance will be assessed using a 75 g oral glucose tolerance test. | 8 weeks | 
| Effect of daily administration of 160 U nasal insulin or placebo over 8 weeks on body composition . | Participants will receive nasal insulin or placebo in a double-blind randomized fashion. Before and after 8 weeks body composition will be addressed by whole-body MRI and liver MRS. | 8 weeks | 
| whole-body insulin sensitivity | Insulin sensitivity will be estimated from a frequent-sampling 75 g oral glucose tolerance test using the Matsuda formula. | 2 hours | 
| Glucose tolerance | a 75 g oral glucose tolerance test will be performed. Glucose tolerance will be defined by the American Diabetes Association criteria. | 2 hours | 
| Cognitive function | cognitive function will be addressed by neuropsychological testing. | 1 hours |