SENSILINS: Impact of Cephalic Phase Insulin Release Induced by an Environmental Food Odor Stimulus on Glucose Homeostasis According to Insulin Sensitivity Level

Impact of Cephalic Phase Insulin Release Induced by an Environmental Food Odor Stimulus on Glucose Homeostasis According to Insulin Sensitivity Level

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.

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.

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