Relative Contribution of Brain Insulin Action for Postprandial Metabolism
- Conditions
- Glucose Metabolism Disorders
- Interventions
- Other: Oral glucose tolerance test with double-tracer dilution and intranasal insulin sprayOther: Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray
- Registration Number
- NCT06295640
- Lead Sponsor
- University of Ulm
- Brief Summary
The goal of this clinical trial is to clarify (i) the contribution of brain insulin action on regulation of systemic metabolism, (ii) sex-specific differences in the central regulation and (iii) the influence of the menstrual cycle in women.
Therefore, participants will undergo oral glucose tolerance tests combined with a double tracer dilution technique. This approach will be compared between days with insulin delivery to the brain as nasal spray and days with placebo spray.
- Detailed Description
This research project aims to investigate to what extent brain insulin action is responsible for the control of postprandial metabolism compared to direct effects of insulin in peripheral target tissues. Furthermore, the study will investigate sex differences and the influence of the menstrual cycle on brain-derived coordination of postprandial signaling for metabolic control.
Therefore, insulin action in the brain will be introduced by application of insulin as nasal spray (on one day) versus carrier solution as placebo nasal spray (on another day) in a randomized, blinded fashion. Spray administration will be performed 15 minutes before a 75 gram oral glucose tolerance test that will introduce a postprandial state. On placebo day, the known spillover of tiny amounts of nasal insulin into the systemic circulation will be mimicked by an appropriate i.v. insulin bolus. This approach will be combined with a double-tracer dilution technique. Labeled glucose (\[6,6-2H\]glucose) will be infused 120 minutes before and during the OGTT (180 min) and will be used to address endogenous glucose production. The glucose drink from the OGTT will be enriched with \[U-13C6\]glucose to compute the glucose appearance rate (Ra). Basal endogenous glucose production will be calculated as well as post-load endogenous glucose production and rates of glucose disappearances (Rd). Using this approach, brain-derived regulation of postprandial metabolism including endogenous glucose production, glucose disappearance, insulin secretion, and secretion of proglucagon-cleavage products (incretins) will be examined.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- BMI < 24 kg/m2
- no known primary diseases
- no hormonal contraception
- Alcohol or drug abuse
- Smoking
- At screening: Hb < 12 g/dl for women and Hb < 14 g/dl for men
- Any (clinical) condition that would endanger participant's safety or question scientific success according to a physician's opinion.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Intranasal insulin spray Oral glucose tolerance test with double-tracer dilution and intranasal insulin spray 160 Units of human insulin as nasal spray Placebo spray Oral glucose tolerance test with double-tracer dilution and intranasal placebo spray Nasal spray containing placebo solution
- Primary Outcome Measures
Name Time Method Endogenous glucose production -120 minutes - 180 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on endogenous glucose production assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
Rate of glucose disappearance -120 minutes - 180 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on rate of glucose disappearance (Rd) assessed with Steele's non-steady state model during an oral glucose tolerance test combined with double-tracer dilution technique.
- Secondary Outcome Measures
Name Time Method Post-absorptive energy expenditure 30 minutes and 180 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on post-absorptive energy expenditure assessed by indirect calorimetry at timepoint 30 min and 180 min during an oral glucose tolerance test combined with double-tracer dilution technique.
Sex differences -120 minutes - 180 minutes during oral glucose tolerance test Explore sex differences in the brain-derived regulation of postprandial metabolism during the 75 g oral glucose tolerance tests. Outcomes 1-7 will be compared between sexes.
Autonomic nervous system activity -15 minutes - 180 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on autonomic nervous system activity assessed by heart rate variability using an 3-channel ECG at timepoint -15 min until 180 min during an oral glucose tolerance test combined with double-tracer dilution technique.
Glucose tolerance 0-120 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on glucose tolerance assessed as area under the glucose curve (0-120 minutes) and glucose levels at timepoint 120 minutes during the 75 g oral glucose tolerance test.
Whole-body insulin sensitivity 0-120 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on whole-body insulin sensitivity, assessed from glucose and insulin measurements during the 75 g OGTT.
Proglucagon cleavage products 0-120 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on secretion of proglucagon cleavage products assessed by oral glucose tolerance test.
Insulin secretion 0-180 minutes during oral glucose tolerance test Effect of intranasal insulin versus placebo on insulin secretion assessed from glucose and insulin/C-peptide measurements during the 75 g oral glucose tolerance test.
Menstrual cycle effects -120 minutes - 180 minutes during oral glucose tolerance test Differences between the follicular and the luteal phase of the menstrual cycle in the brain-derived regulation of postprandial metabolism during the 75 g oral glucose tolerance tests: Outcomes 1-7 will be compared between the phases of the menstrual cycle.
Trial Locations
- Locations (1)
Universityhospital Ulm
🇩🇪Ulm, Germany