Influence of Central Nervous Insulin Action on Insulin Sensitivity of Peripheral Organs in Lean Versus Overweight Humans

Not Applicable

Completed

• Conditions: Insulin Resistance
• Interventions: Drug: human insulin

• Registration Number: NCT02468999
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

Research in animals and first experiments in humans indicate that insulin action in the brain regulates peripheral insulin sensitivity. One major organ might be the liver. Previous studies in humans showed that the human brain is an insulin sensitive organ in lean but not in overweight/obese persons. Therefore, this study will include lean versus overweight/obese persons.

In this study, insulin action will be introduced by intranasal insulin administration in lean and overweight humans. As a control, placebo spray will be administered. To mimick the known spill over of small amounts of intranasal insulin into circulation, a small bolus of insulin will be administered over 15 minutes following placebo spray application.

Peripheral insulin sensitivity will be assessed by hyperinsulinemic-euglycemic glucose clamp and glucose uptake and endogenous glucose production will be assessed by tracer dilution technique. Autonomous nervous system activity will be addressed by heart rate variability. Involved brain areas will be addressed by fMRI before and after nasal insulin application.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01
• Study First Submitted: 2015-03-24
• Study First Submitted QC: 2015-06-08
• Study First Posted: 2015-06-11
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-01
• Last Update Submitted: 2016-01-07
• Last Update Posted: 2016-01-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 21

Inclusion Criteria

• Male volunteers (lean or overweight/obese)
• HbA1c <6.0%
• Age between 18 and 40 years
• healthy as assessed by physician
• Understanding the explanations about the study and instructions

Exclusion Criteria

• non-removable metal parts in or on the body
• Persons with reduced temperature sensation and / or increased sensitivity to warming of the body
• Cardiovascular disease can not be excluded, such as evident coronary heart disease, congestive heart failure NYHA greater than 2, history of coronary artery disease
• History of stroke
• Persons with a hearing disorder or increased sensitivity to loud noises
• People with claustrophobia
• Subjects in which less than 3 months have passed since surgery
• Simultaneous participation in other studies
• Acute disease or infection within the last 4 weeks
• Neurological and psychiatric disorders
• Subjects with hemoglobin Hb <13g / dl
• Heparin-induced thrombocytopenia people with a (HIT) in prehistory
• Allergies to any of the used solutions/devices

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
placebo nasal spray	human insulin	Nasal spray containing placebo solution
insulin nasal spray	human insulin	160 Units of human insulin as nasal spray

Primary Outcome Measures

Name	Time	Method
Change in endogenous glucose production from before to after nasal spray application in lean persons	Change from 70-90 min (before spray) to 170-210 min and to 280-300 min	Will be assessed by tracer dilution technique.
Change in glucose infusion rate during hyperinsulinemic euglycemic glucose clamp from before to after nasal spray application in lean persons	Change from 70-90 min (before spray) to 170-210 min and to 280-300 min
Differences in insulin response between lean and overweight persons	up to 210 minutes post nasal spray administration	Will be assessed as plasma insulin and C-peptide concentrations.

Secondary Outcome Measures

Name	Time	Method
Autonomous nervous system activity	baseline, 70-90 min, 170-210 min and 280-300 min	Will be assessed by analysis of heart rate variability.
Regional brain insulin sensitivity	30 min	Will be assessed on an additional study day by fMRI before and after intranasal insulin administration

Trial Locations

Locations (1)

University of Tuebingen, Department of Internal Medicine IV; 🇩🇪 Tübingen, Germany