Insulin Resistance Syndrome, Obesity & Overweight
Conditions
Keywords
Glucose Homeostasis, Cephalic Phase Insulin Release, Food odor, Olfaction, Oral glucose tolerance test, Insulin secretion, GLP-1
Brief summary
This single-center, randomized, single-blind, 2-period crossover interventional study will evaluate whether exposure to a pleasant food odor 10 minutes before a 75 g oral glucose tolerance test (OGTT) modifies glucose homeostasis in adults with different metabolic phenotypes. Participants will undergo two experimental conditions in random order: food odor stimulation and control condition without odor, separated by a 4-week washout. The main objective is to quantify the within-subject effect of food odor stimulation on the incremental area under the glucose curve (iAUC) from 0 to 120 minutes during OGTT and to assess whether this effect differs according to metabolic status. Two predefined groups will be enrolled: adults without overweight and without insulin resistance, and adults with class I obesity and low-to-moderate insulin resistance. Secondary objectives include characterization of cephalic phase insulin release (CPIR), C-peptide and GLP-1 responses, glycemic kinetics, associations between CPIR and metabolic responses, and participant acceptability of the test environment and olfactory stimulation. A plasma biobank will be constituted from part of the collected samples for future research.
Detailed description
Recent experimental and translational data suggest that olfactory cues may contribute to metabolic regulation through anticipatory cephalic phase responses. Cephalic phase insulin release (CPIR) is an early preabsorptive insulin response triggered by sensory food-related stimuli before nutrient absorption. Preclinical data generated by the study team suggest that food-odor-induced CPIR involves an olfactory bulb-pancreas axis and may be altered in obesity. The present study is designed to investigate, in humans, whether a pleasant appetitive food odor delivered before glucose ingestion can induce measurable CPIR and improve post-load glucose handling. The study uses a randomized AB/BA crossover design with two experimental visits after screening and inclusion. During one visit, participants are exposed to prerecorded food odor diffusion using a ScentRealm collar starting at T-10 minutes before ingestion of a 75 g glucose solution at T0. During the control visit, the same testing environment is maintained without odor stimulation. Serial blood sampling is performed before and after glucose ingestion to characterize glucose, insulin, C-peptide, and GLP-1 kinetics. The washout period is 4 weeks (±3 days), partly to align visits within the same menstrual cycle phase in women when applicable. The trial includes 20 adults aged 18 to 50 years: 10 without overweight and insulin-sensitive, and 10 with obesity and low-to-moderate insulin resistance defined using HOMA-IR.
Interventions
BEHAVIORALPleasant Food Odor Stimulation
Exposure to an experimentally selected appetitive food odor (madeleine odor) delivered using a programmable ScentRealm collar in a standardized test room beginning at T-10 minutes before OGTT.
BEHAVIORALControl Environmental Condition
Standardized testing environment identical to the experimental visit but without diffusion of the appetitive food odor.
Sponsors
Hospices Civils de Lyon
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Masking description
Participants are not informed before study completion that the difference between the two test visits concerns the olfactory environment. The test room, staff interaction rules, music, and visual setting are standardized across visits to minimize expectancy effects.
Intervention model description
Two-period, two-sequence crossover study (AB/BA) comparing food odor stimulation versus control condition during an OGTT. Randomization is stratified by sex and metabolic group, with restricted permuted blocks of variable size. The washout period between study periods is 4 weeks (±3 days).
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 50 years inclusive * Stable body weight during the previous 3 months (±5% of total body weight) * Willing to comply with the full study protocol * Sedentary lifestyle or stable regular physical activity, with agreement to keep this unchanged throughout the study * Able to understand study information, read and write French, and provide written informed consent * Affiliated with a social security scheme or equivalent * Non-smoker and non-vaper * Willing not to take dietary supplements, probiotics, prebiotics, or laxatives for 10 days before each visit * For women of childbearing potential: negative serum pregnancy test; not pregnant and not breastfeeding * Mean score between 1 and 2 on the 3 specific CiTAS questionnaire statements used as inclusion criteria * ETOC flash olfactory screening: able to detect the odor-containing vial among 4 presented vials for all 7 odors tested * Able to identify the madeleine odor used in the study * Rated pleasantness/appetence of the madeleine odor above 1/9 * For the no-overweight group: BMI 19 to \<25 kg/m² and HOMA-IR \<1.7 * For the obesity group: BMI 30 to \<35 kg/m² and low-to-moderate insulin resistance based on HOMA-IR \[protocol inconsistency to resolve; see note below\]
Exclusion criteria
* Unstable medical or psychological conditions that could impair compliance, safety, or study participation in the investigator's judgment * Alcohol consumption \>30 g/day, or established abuse/dependence on another drug * Ongoing exclusion period from another study listed in the national volunteer file * Legal protection measure (guardianship/curatorship) * Deprivation of liberty by judicial or administrative decision * Exceeded annual compensation limit for research participation * Lack of valid required health documentation in the event of exceptional governmental epidemic measures * Blood donation within 2 months before inclusion visit * Limited venous access making repeated blood sampling/catheter placement difficult * Current or permanent anosmia or olfactory disorder * Type 1 or type 2 diabetes, treated or untreated * History of gestational diabetes * Known or treated hypertension * Blood pressure \>160 \[unit missing; likely mmHg systolic threshold\] * Dyslipidemia, treated or untreated * Triglycerides \>3 mmol/L * Allergic rhinitis * Nasosinusal polyposis * History of intestinal or abdominal surgery except appendectomy or simple hernia repair * History of ENT or neurological surgery * Severe eating disorder (for example anorexia, bulimia, binge-eating disorder, night eating) * Any pathology detected on clinical examination or medical interview judged by the investigator to interfere with study endpoints or participant safety * Any biological abnormality judged by the investigator to interfere with study endpoints or participant safety * Use of treatments likely to interfere with study measurements, for example antidepressants, antiepileptics, neuroleptics, CPAP treatment for sleep apnea, nasal spray medications, or anti-obesity drug treatment, according to investigator judgment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Within-subject difference in glucose incremental area under the curve (iAUC) from 0 to 120 minutes during OGTT | During each experimental visit, from 0 to 120 minutes after ingestion of the 75 g oral glucose load | Primary endpoint is the mean within-subject difference between food odor and control conditions in glucose incremental area under the curve from 0 to 120 minutes after oral glucose ingestion. Glucose iAUC will be calculated using the trapezoidal method, baseline-adjusted to glucose at T0. The main analysis will also assess the interaction between condition (odor vs control) and metabolic status (no overweight/insulin-sensitive vs obesity with low-to-moderate insulin resistance). Unit should be specified in the statistical analysis plan according to assay reporting (for example mmol/L×min or mg/dL×min). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preabsorptive and early post-ingestion insulin iAUC as a measure of cephalic phase insulin release | From pre-OGTT odor exposure through 15 minutes after glucose ingestion during each experimental visit | Incremental area under the curve for insulin during the pre-ingestion and early post-ingestion period (0 to 15 minutes), compared by condition and metabolic status. Additional CPIR-related metrics include latency, peak concentration, slope, and percentage of responders. Unit to specify according to assay output (for example µIU/mL×min or pmol/L×min). |
| Preabsorptive and early post-ingestion C-peptide iAUC | From pre-OGTT odor exposure through 15 minutes after glucose ingestion during each experimental visit | Incremental area under the curve for C-peptide during the pre-ingestion and early post-ingestion period (0 to 15 minutes), compared by condition and metabolic status. Additional metrics include latency, peak concentration, slope, and percentage of responders. Unit to specify according to assay output. |
| Glycemic kinetic response during OGTT - Δmax | From 0 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on glycemic maximum change from baseline (Δmax) |
| Glycemic kinetic response during OGTT - Time to peak | From 0 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on the necessary amount of time to reach glycemic peak in minutes |
| Glycemic kinetic response during OGTT - Growth curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on the slope of the glycemic growth curve from baseline |
| Glycemic kinetic response during OGTT - Decay curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on the slope of the glycemic decay curve from the maximum (peak) |
| Glycemic kinetic response during OGTT - ultradian oscillation indices | From 0 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on ultradian oscillation indices |
| Glycemic kinetic response during OGTT - iAUC (0 to 120 min) | From 0 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on Incremental Area Under the Curve (IAUC) from 0 to 120 min for glucose |
| Glycemic kinetic response during OGTT - early glucose iAUC (0-30min) | From 0 to 30 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on glucose Incremental Area Under the Curve (IAUC) from 0 to 30 min |
| Glycemic kinetic response during OGTT - late glucose iAUC (30-120 min) | From 30 to 120 minutes after glucose ingestion during each experimental visit | Effect of condition and metabolic status on glucose Incremental Area Under the Curve (IAUC) from 30 to 120 min |
| Hormonal response parameters for insulin during OGTT - iAUC (0-120 min) | From 0 to 120 minutes after glucose ingestion during each experimental visit | Total Incremental Area Under the Curve (iAUC) from 0 to 120 minutes |
| Hormonal response parameters for insulin during OGTT - iAUC (0-30min) | From 0 to 30 minutes after glucose ingestion during each experimental visit | Insulin Incremental Area Under the Curve (IAUC) from 0 to 30 min |
| Hormonal response parameters for insulin during OGTT - iAUC (30-120min) | From 30 to 120 minutes after glucose ingestion during each experimental visit | Insulin Incremental Area Under the Curve (IAUC) from 30 to 120 min |
| Hormonal response parameters for insulin during OGTT - Δmax | From 0 to 120 minutes after glucose ingestion during each experimental visit | The value of the maximum (peak) of the curve relative to the baseline value for insulin |
| Hormonal response parameters for insulin during OGTT - Time to peak | From 0 to 120 minutes after glucose ingestion during each experimental visit | Necessary amount of time for insulin to reach peak in minutes |
| Hormonal response parameters for insulin during OGTT - Growth curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Slope of the insulin growth curve from baseline |
| Hormonal response parameters for insulin during OGTT - Decay curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Slope of the insulin decay curve from the maximum (peak) |
| Hormonal response parameters for C-peptide during OGTT - iAUC (0-120min) | From 0 to 120 minutes after glucose ingestion during each experimental visit | C-peptide Incremental Area Under the Curve (IAUC) from 0 to 120 min |
| Hormonal response parameters for C-peptide during OGTT - iAUC (0-30min) | From 0 to 30 minutes after glucose ingestion during each experimental visit | C-peptide Incremental Area Under the Curve (IAUC) from 0 to 30 min |
| Hormonal response parameters for C-peptide during OGTT - iAUC (30-120min) | From 30 to 120 minutes after glucose ingestion during each experimental visit | C-peptide Incremental Area Under the Curve (IAUC) from 30 to 120 min |
| Hormonal response parameters for C-peptide during OGTT - Δmax | From 0 to 120 minutes after glucose ingestion during each experimental visit | The value of the maximum (peak) of the curve relative to the baseline value for C-peptide |
| Hormonal response parameters for C-peptide during OGTT - Time to peak | From 0 to 120 minutes after glucose ingestion during each experimental visit | Necessary amount of time for C-peptide to reach peak in minutes |
| Hormonal response parameters for C-peptide during OGTT - Growth curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Slope of the C-peptide growth curve from baseline |
| Hormonal response parameters for C-peptide during OGTT - Decay curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Slope of the C-peptide decay curve from the maximum (peak) |
| Hormonal response parameters for GLP-1 during OGTT - iAUC (0-120min) | From 0 to 120 minutes after glucose ingestion during each experimental visit | GLP1 Incremental Area Under the Curve (IAUC) from 0 to 120 min |
| Hormonal response parameters for GLP-1 during OGTT - iAUC (0-30min) | From 0 to 30 minutes after glucose ingestion during each experimental visit | GLP-1 Incremental Area Under the Curve (IAUC) from 0 to 30 min |
| Hormonal response parameters for GLP-1 during OGTT - iAUC (30-120min) | From 30 to 120 minutes after glucose ingestion during each experimental visit | GLP-1 Incremental Area Under the Curve (IAUC) from 30 to 120 min |
| Hormonal response parameters for GLP-1 during OGTT - Δmax | From 0 to 120 minutes after glucose ingestion during each experimental visit | The value of the maximum (peak) of the curve relative to the baseline value for GLP-1 |
| Hormonal response parameters for GLP-1 during OGTT - Time to peak | From 0 to 120 minutes after glucose ingestion during each experimental visit | Necessary amount of time for GLP-1 to reach peak in minutes |
| Hormonal response parameters for GLP-1 during OGTT - Growth curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Slope of the GLP-1 growth curve from baseline |
| Hormonal response parameters for GLP-1 during OGTT - Decay curve slope | From 0 to 120 minutes after glucose ingestion during each experimental visit | Slope of the GLP-1 decay curve from the maximum (peak) |
| Correlation between CPIR characteristics and metabolic/hormonal responses | Assessed using measurements collected during each experimental visit up to 120 minutes after glucose ingestion | Correlations between CPIR features and subsequent glucose response during OGTT (including glucose iAUC 0-120 and early/late components) and hormonal quantitative/kinetic responses, including assessment of interaction with metabolic status. |
| Participant-rated appreciation of the experimental odor | Week 2 ; Week 4 | Appreciation of the experimental odor and related emotions assessed using Likert scales at the end of the odor visit, with comparison by condition and metabolic status where applicable. Exact scale range and anchor wording are not provided in the available protocol text. |
| Participant-rated acceptability of the test environment - Temperature | Week 2 ; Week 4 | Acceptability and appreciation of the temperature of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires. |
| Participant-rated acceptability of the test environment - Lighting | Week 2 ; Week 4 | Acceptability and appreciation of the lighting of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires. |
| Participant-rated acceptability of the test environment - Sound | Week 2 ; Week 4 | Acceptability and appreciation of the sound of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires. |
| Participant-rated acceptability of the test environment - Odor | Week 2 ; Week 4 | Acceptability and appreciation of the odor of the environment assessed using Likert scales and free-text fields. Comparison by condition and metabolic status. Scale range should be entered exactly as used in source questionnaires. |
Countries
France
Contacts
CONTACTAnne Laure MD CASTELL, Dr
Outcome results
None listed