Zentrale Insulinsensitivität Bei Personen Mit Typ-2-Diabetes Sowie Bei Personen Mit erhöhtem Risiko für Die Entwicklung Von Typ-2-Diabetes
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Central Insulin Resistance
- Sponsor
- University Hospital Tuebingen
- Enrollment
- 180
- Locations
- 1
- Primary Endpoint
- Comparison of brain insulin sensitivity in different age, weight, sex and metabolic risk groups
- Status
- Recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •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)
Outcomes
Primary Outcomes
Comparison of brain insulin sensitivity in different age, weight, sex and metabolic risk groups
Time Frame: 30 minutes after Administration of nasal insulin
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).
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)
Time Frame: 45 minutes
CANTAB test will be performed
Comparison of the blood-brain-barrier permeability in different age, weight, sex and metabolic risk groups
Time Frame: 30 minutes after Administration of nasal insulin
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).