Effects of Reactive Hypoglycaemia on Cognition in Earlier or Later Chronotypes

Summary

Studies suggest a link between lower postprandial glycaemic response and better cognitive performance in children, adolescents, and young adults, though evidence remains inconclusive. High glycaemic index (GI) meals quickly raise blood glucose, potentially causing reactive hypoglycaemia (glucose levels below baseline) and harming cognitive performance, especially in the late postprandial period, particularly after 120 minutes. Young adults may be more sensitive to these cognitive effects due to morning circadian misalignment, as their sleep midpoint (chronotype) is biologically most delayed. Recent research suggests that those with later chronotypes do not display the known circadian decline in glucose tolerance as indicated by equally high glycaemic responses to the same high GI meal in the morning or the evening. Eating breakfast "against the inner clock" may harm glycaemic response, particularly for those with a later chronotype. Those with morning circadian misalignment may also limit breakfast to beverages. Reactive hypoglycaemia commonly follows beverage consumption, especially soft drinks, energy drinks, glucose solutions, and low-GI fruit juices, occurring within 60 minutes after consumption. Later chronotypes may be more prone to reactive hypoglycaemia from drinks, harming cognition. This nutrition trial aims to investigate (I) the effects of breakfast-induced reactive hypoglycaemia on memory and attention in young, healthy, non-obese university students and (II) the relevance of chronotype to hypoglycaemia occurrence. To study reactive hypoglycaemia, a low GI beverage will be used, causing hypoglycaemia despite a low glycaemic response. Two samples will be examined: students of early and late chronotype. Postprandial insulin and cortisol changes will be analyzed, as improved insulin sensitivity and cortisol levels seem to affect cognition. From October 2024 to January 2025, 356 students (ages 18-25) enrolled in the GlyCoBrain Observational study (ID: NCT06679088) and were screened for chronotypes at Paderborn University. Participants with extreme chronotypes will be invited to this crossover study. Power calculations indicated a sample of 88 participants who complete both intervention days. They will consume a low-GI beverage at 9 a.m. causing reactive hypoglycaemia (glucose-fructose-sucrose solution) or a non-hypoglycaemia causing beverage (isomaltulose® solution) and undergo repeated cognitive assessments for the following 180 minutes.

Conditions

• Healthy

Interventions

OTHER

immediate verbal memory after low glycemic index breakfast inducing no reactive hypoglycaemia

\- Difference in immediate verbal memory after low GI breakfast without reactive hypoglycaemia at 90minutes

OTHER

immediate verbal memory after low glycemic index breakfast causing reactive hypoglycaemia

\- Difference in immediate verbal memory after low GI breakfast causing reactive hypoglycaemia at 90 minutes

Sponsors & Collaborators

• Paderborn University

  collaborator OTHER

• University of Southern Denmark

  collaborator OTHER

• Anette Buyken

  lead OTHER

Principal Investigators

• Lars Libuda, Prof. Dr., Prof. Dr. · Paderborn University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Max Age

25 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-04-04

Primary Completion

2026-03-31

Completion

2027-07-31

Countries

• Germany

Study Locations