Central Insulin Sensitivity in Individuals With Type 2 Diabetes (T2D) and at Risk for Developing T2D

NCT05856877 | Recruiting

• 1 other identifier: INCLU
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

Beside well described peripheral effects, insulin can also affect the human central nervous system. Centrally acting insulin seems to have an influence e.g. on whole-body metabolism and food intake. Targeting insulin receptors in the central nervous system can modulate peripheral insulin sensitivity as well as pancreatic insulin secretion. In humans, the effect of insulin can be measured in different brain areas as estimate of central nervous insulin sensitivity. Reduced central nervous insulin sensitivity, called "central insulin resistance," has been associated, for example, with obesity, unfavorable body fat distribution, and impaired cognitive functionality. Recently novel subtypes and risk clusters of diabetes and prediabetes have been identified. In this study the investigators want to investigate and compare central nervous insulin sensitivity as well as cognitive function in the different diabetes and prediabetes risk clusters.

Conditions

Central Insulin Resistance; Diabetes Mellitus, Type 2; PreDiabetes

Outcome Measures

Primary Outcomes (3)

• Comparison of brain insulin sensitivity in different age, weight, sex and metabolic risk groups

  fMRI measurement will be performed before and after administration of 160 U human insulin or placebo as nasal spray. Changes in regional brain activity will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess regional brain insulin sensitivity. Brain insulin sensitivity will be compared between 5 groups (T2DM-high risk group, T2DM-low risk group, elevated risk for developing T2DM-high risk group, elevated risk for developing T2DM-low risk group, lean and healthy group). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split. Metabolic risk groups are build based on Ahlqvist-criteria (T2DM) and based on Wagner-criteria (elevated risk for developing T2DM).

  30 minutes after Administration of nasal insulin

• Comparison of cognitive function between subtype clusters of different metabolic groups (increased risk for developing manifest type 2 diabetes cluster, manifest type 2 diabetes cluster)

  CANTAB test will be performed

  45 minutes

• Comparison of the blood-brain-barrier permeability in different age, weight, sex and metabolic risk groups

  fMRI measurement will be performed before and after administration of 160 U human insulin or placebo as nasal spray. Changes in blood-brain-barrier permeability will be quantified by cerebral blood flow and blood oxygenation dependent (BOLD) signal to assess blood-brain-barrier permeability. blood-brain-barrier permeability will be compared between 5 groups (T2DM-high risk group, T2DM-low risk group, elevated risk for developing T2DM-high risk group, elevated risk for developing T2DM-low risk group, lean and healthy group). Persons are categorized into normal weight and overweight/obese based on the Body Mass Index (BMI). Age groups are build based on a median split. Metabolic risk groups are build based on Ahlqvist-criteria (T2DM) and based on Wagner-criteria (elevated risk for developing T2DM).

  30 minutes after Administration of nasal insulin

Study Arms (2)

Nasal insulin spray

ACTIVE COMPARATOR

Other: Human nasal insulin

Placebo spray

PLACEBO COMPARATOR

Other: Placebo

Interventions

Human nasal insulin OTHER

single dose of 160 U of human insulin as nasal spray

Nasal insulin spray

Placebo OTHER

Single dose of placebo solution as nasal spray

Placebo spray

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• manifest diabetes mellitus type 2 with initial diagnosis ≤ 10 years ago, defined as
• a fasting blood glucose greater than 126 mg/dl and/or
• a blood glucose greater than 200 mg/dl at the 120 minute time point in the oral glucose tolerance test with 75 g glucose and/or
• an HbA1c greater than 6.5%
• or a currently existing increased risk of developing type 2 diabetes, defined as
• prediabetes, defined as
• elevated fasting blood glucose (IFG), fasting blood glucose between 100 and 125 mg/dl) and/or
• impaired glucose tolerance (IGT), 120-minute oral glucose tolerance test blood glucose between 140 and 199 mg/dl) and/or
• HbA1c between 5.7% and 6.4% with
• and/or at least one of the following factors indicating an increased risk for developing type 2 diabetes mellitus:
• previously existing prediabetes and/or
• recent-onset gestational diabetes, and/or
• positive family history (1st degree family members) for type 2 diabetes mellitus and/or
• BMI greater than 27 kg/m2
• or no manifest diabetes mellitus type 2 and no currently existing increased risk for developing type 2 diabetes (control group: BMI 18.5 to 24.5 kg/m2)

You may not qualify if:

• Only in subjects without manifest diabetes mellitus type 2: Taking medications that affect sugar metabolism (e.g., antidiabetic medications or glucocorticoids).
• Diabetes mellitus type 1 or Latent autoimmune diabetes in the adult (GAD and/or IA2 antibodies positive)
• MODY (Maturity onset Diabetes of the Young)
• Decompensated diabetes mellitus type 2 (HbA1c greater than 9.6% and/or fasting blood glucose \> 230 mg/dl)
• BMI \< 18.5 or \> 45 kg/m2
• Individuals wearing non-removable metal devices in or on the body such as:
• pacemakers
• artificial heart valves
• metal prostheses
• implanted magnetic metal parts (screws, plates from surgery)
• coils
• metal splinters/garnet chips
• fixed braces
• retainers going over more than four teeth
• acupuncture needle

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tübingen

Tübingen, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Prediabetic State

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Stephanie Kullmann, Prof.

CONTACT

070712987702; stephanie.kullmann@med.uni-tuebingen.de

Christian Kübler, Dr.

CONTACT

070712968784; christian.kuebler@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: May 12, 2023
• Study Start: May 26, 2023
• Primary Completion: May 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 14, 2024

Record last verified: 2024-05

Locations

DE (1)