The Effect of Central Insulin on Insulin Sensitivity and Energy Metabolism

Phase 4

Completed

• Conditions: Diabetes
• Interventions: Drug: intransal insulin; Drug: Placebo; Device: taVNS; Device: sham stimulation

• Registration Number: NCT01479075
• Lead Sponsor: German Diabetes Center

Brief Summary

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism and the secretion of various hormone. The effect of intranasal insulin on peripheral metabolism in humans supposedly is mediated by the vagus nerve.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and whether vagus nerve stimulation can mimick this effect.

Detailed Description

Insulin has a direct effect on the energy metabolism of the brain under basal conditions and has an effect on the hepatic glucose production, lipid metabolism in the mouse model.

The purpose of this study is to determine whether central insulin influences the human peripheral insulin sensitivity of liver and muscle and energy metabolism. Intranasal insulin can be used in humans to deliver insulin to the brain and studies have shown that intranasal insulin might reduce food intake, lower body weight and modulate muscle glucose and adipose tissue lipid metabolism in himans. These effects are likely mediated by the vagus nerve as skeletal muscle insulin sensitization after intranasal insulin relates to parasympathetic tone activity (Heni et al. Diabetes 2014). Transcutaneous auricular vagus nerve stimulation (taVNS) activates non-invasively the sensory branches of the vagus nerve and is applied in humans as adjuvant treatment in drug-resistant epilepsy (Frangos et al. 2015). Thereby it can be used to examine whether the vagus nerve indeed mediates brain insulin signals to the periphery.

Here we aim to investigate the effects of intranasal insulin on hepatic glucose, lipid and energy metabolism. We further aim to test whether taVNS can mimick intranasal insulin effects on peripheral metabolism in humans.

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-11-22
• Study First Submitted QC: 2011-11-23
• Study First Posted: 2011-11-24
• Primary Completion: 2014-01
• Study Completion: 2014-06
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-02
• Last Update Posted: 2023-06-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Age ≥ 30 and ≤ 70 years
• balanced gender ratio (50: 50)
• BMI 20-25 kg/m² (normal weight subjects)
• BMI 25-35 kg/m² (obese subjects)

Exclusion Criteria

• acute illness within the last 2 weeks before the examination
• autoimmune diseases and disorders immune- compromised (leukocytes <5000/μl)
• renal insufficiency (creatinine> 1.5 mg / dl)
• heart disease, condition after heart attack
• anemia (Hb <12 g / l, controls at each examination), blood donation within 4 weeks before the examination
• participation in another study within 2 months before the examination
• wear a metal or magnetic objects on or in the body
• claustrophobia
• use of immunomodulatory drugs (cortisol, antihistamines, aspirin)
• thyroid disease
• taking glitazones and insulin therapy
• pregnancy, lactation, menstruation
• cigarette smoking, use of alcohol or drugs, psychiatric disorders
• risk for / or manifest AIDS (HIV) or hepatitis B or C
• liver disease is not attributed to the existence of a non-alcoholic steatosis
• night shift work or circumstances, which do not allow the normal day-night rhythm
• bleeding disorders or disorders in wound healing
• hypersensitivity to local anesthetics
• malignant cancer
• heart rhythm disorders
• polyneuropathy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
intranasal insulin in patients	intransal insulin	intranasal insulin is applied to diabetic patients under fasting conditions
intransal insulin in study participants	intransal insulin	intranasal insulin is applied to healthy patients under fasting conditions
placebo in patients	Placebo	placebo spray is applied intranasally in type 2 diabetes patients under fasting conditions
placebo in study participants	Placebo	placebo spray is applied intranasally in healthy participants under fasting conditions
taNVS	taVNS	Transcutanoues auricular vagus nerve stimulation is applied for 14 min in the external ear in healthy participants
Sham stimulation	sham stimulation	Sham stimulation in the ear lobe is applied for 14 min in healthy participants

Primary Outcome Measures

Name	Time	Method
Insulin sensitivity	6 months	Assessment of insulin sensitivity with gold standard methods

Secondary Outcome Measures

Name	Time	Method
Energy metabolism	6 months	Energy metabolism is assessed from gold standard methods

Trial Locations

Locations (1)

German Diabetic Center; 🇩🇪 Düsseldorf, Nordrhein- Westfalen, Germany