Nutrition Trial on the Glycaemic Response to High GI Meals Consumed at Morning vs. Evening-The ChroNu Study

To address the hypothesis that dietary misalignment among young adults has detrimental short-term effects on glucose metabolism, participants will consume a meal rich in high GI carbohydrates on two separate days either at breakfast (7:00) or at dinner (20:00). Glycaemic responses will be monitored by a continuous glucose monitoring device (CGM) (G6, Dexcom, Inc., San Diego, CA). The CGM electrochemically measures subcutaneous interstitial glucose concentrations of each participant during the whole study. A blood glucose meter will be used to verify the functionality of the CGM (CONTOUR®NEXT ONE).

The caloric content of the meals will be tailored to the energy needs of the participants based on their age, sex and anthropometric measurements. Participants will be requested to consume the meals without any break. During the controlled nutrition trial, participants will be asked to abstain from alcohol consumption and heavy exercise and not consume any food in addition to that provided or drinks that should be explicitly avoided.

To objectively corroborate their chronotype participants will be asked to wear an accelerometer (E4 wristband, Empatica) attached to the wrist during the controlled nutrition trial. Moreover, participants are asked to record their bed times, meal timings, daily routines, and physical activities during the trial. On day 1 and day 8, anthropometric measurements will be performed to compare the body composition (Bioimpedance Analysis, SECA mBCA) before and after the controlled nutrition trial. On day 4, fasting blood samples will be collected. Before the controlled nutrition trial will start, questionnaires on daily routines, food frequency, and chronotype will be carried out.

The chronotype is defined as mid-sleep point and assessed by the Munich Chronotype Questionnaire, which is a validated questionnaire. Earlier and later chronotypes will be defined as 20% of the participants with each the earliest and later mid-sleep points among the participants of the ChroNu cohort.

• Glycaemic response to high GI carbohydrates consumed at morning versus evening meals. (Other): Controlled nutrition trial on the glycaemic response to morning and evening meals with high glycemic index carbohydrates among students with early and late chronotypes.

Primary outcomes

• Differences in the 2-h pp glycaemic response between the high GI carbohydrate meal consumed for breakfast (7:00) and the high GI carbohydrate meal consumed for dinner (20:00). [2 hour postprandial after test meals]: 2 hour post prandial response (iAUC) is calculated as the incremental area under the curve of measurements taken within the two hours after the test meals.
• Differences in the 2-h pp glycaemic variability between the high GI carbohydrate meal consumed for breakfast (7:00) and the high GI carbohydrate meal consumed for dinner (20:00). [2 hours postprandial after test meals]: the 2-h pp glycaemic variability (MAGE) is calculated as the mean amplitude of glycaemic excursions during the two hours after the test meals, i.e. both resemble summary measures calculated from repeated measurements taken the 2 h pp.

Secondary outcomes

• Diurnal differences in the glycaemic response (iAUC) and in response to the high GI carbohydrates for dinner and the high GI carbohydrates for breakfast. [24 hours after test meals]: 24 hour post prandial response (iAUC) is calculated as the incremental area under the curve of measurements taken within the 24 hours after the test meals.
• Diurnal differences in the glycaemic variability (MAGE) in response to the high GI carbohydrates for dinner and the high GI carbohydrates for breakfast. [24 hours after test meals]: 24-h pp glycaemic variability (MAGE) is calculated as the mean amplitude of glycaemic excursions during the 24 hours after the test meals, i.e. both resemble summary measures calculated from repeated measurements taken the 24 h pp.

Other outcomes

• Blood lipids, inflammation marker, and glucose homeostasis [7:30 on run-in day]: Blood lipids, markers of chronic inflammation, and glucose homeostasis will be measured from serum or plasma obtained from fasting whole blood samples. * total cholesterol (mmol/L) * triglycerides (mmol/L) * LDL- cholesterol (mmol/L) * HDL- cholesterol (mmol/L * small-dense LDL (mmol/L) * small-dense HDL (mmol/L) * high-sensitivity C-reactive protein (mmol/L) * Fasting blood glucose (mmol/L)
• Insulin level [7:30 run-in day]: \- fasting plasma insulin level (µE/mL)
• Liver enzymes [7:30 run-in day]: * Alanine transaminase (U/L) * γ- Glutamyltransferase (U/L)
• Clock gene expression [7:30 run-in day]
• Sleep timing [8 days]: Sleep timing (unit) will be determined using an accelerometer (Empatica E4) and manually kept diary during the 8 days of nutrition trial. This information will serve to to corroborate the chronotype of the participants.
• Change in fat mass [at baseline (day 1) and after intervention (day 8)]: Body composition is electronically analyzed using Bioimpedance Analysis (BIA) (mBCA 515, SECA).
• Change in Body Mass Index [at baseline (day 1) and after intervention (day 8)]: Body Mass Index (BMI) is calculated by weight(kg) / height(m)²). Weight and height are measured electronically.

Sex: All, ages: 18 Years to 25 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy students of Paderborn University
* 18 - 25 years old at time of screening for the ChroNu cohort
* 18,5 kg/m² < BMI > 30 kg/m²
* Free of diseases requiring constant or chronic medical treatment (except for oral contraceptives)
* Willingness to participate in the nutrition trial (8 days) including invasive measurements
* Fluent knowledge of the German language

Exclusion Criteria:

* students studying nutrition science at the University Paderborn
* regular smokers
* pregnancy or lactation
* chronic diseases: diabetes mellitus (all types), pre-diabetes, individuals with bleeding disorders (thrombocytopenia, haemophilia)
* contact dermatitis to adhesive plaster or skin disease that prevents the participant from wearing the CGM
* intake of medication which influence the chronotype: such as antidepressants or sleeping pills
* shift work in the past 3 months
* crossing of > 1-time zone in the past 3 months
* strict vegetarians /vegans
* individuals having an allergy or intolerance to food that is included in the diet

• Results publication: Stutz B, Krueger B, Goletzke J, Jankovic N, Alexy U, Herder C, Dierkes J, Berg-Beckhoff G, Jakobsmeyer R, Reinsberger C, Buyken AE. Glycemic response to meals with a high glycemic index differs between morning and evening: a randomized cross-over controlled trial among students with early or late chronotype. Eur J Nutr. 2024 Aug;63(5):1593-1604. doi: 10.1007/s00394-024-03372-4. Epub 2024 Apr 12. PMID 38605233

• Anette E Buyken, Prof. Dr., Principal investigator, Paderborn University