Overview
Glycemic responses vary significantly among individuals, even when consuming identical foods or meals, but the factors predicting individual glucose response to food intake remain poorly investigated.
The aim of the LIfestyle MEtabotype study (LIME) observational study is to identify lifestyle-related and mechanistic factors which predict individual postprandial glucose fluctuations in individuals with different glycemic status (prediabetes, type 2 diabetes \[T2D\], and absence of prediabetes or T2D). To address this aim, the study will conduct a comprehensive lifestyle characterization and metabolic, molecular and neurocognitive phenotyping during study center visits and a dietary, glucose, sleep and activity monitoring during the observational phase.
Description
Studies show that glycemic responses vary significantly among individuals, even when consuming identical foods or meals. These varying glycemic responses are attributed to metabolic differences between individuals. Recently, machine learning models incorporating metabolic data (including microbiome composition) have been able to successfully predict individual blood glucose responses. Precision nutrition recommendations based on such predictions could facilitate better glycemic control and reduce the risk of diabetes. From this perspective, considering metabolic biomarkers, phenotype and genotype, as well as gut microbiome composition, could play a role in deriving dietary recommendations and thereby achieving the best possible health outcomes through nutrition. In addition to macronutrient composition, the timing, frequency and number of meals may also play a significant role in the glycemic response to diet. Finally, socioeconomic, cultural and personal lifestyle factors also have an influence on the glycemic response. Therefore, this study aims to characterize the personal lifestyle differences between individuals with prediabetes, T2D, and those without prediabetes or T2D.
Furthermore, ketone bodies, specifically β-hydroxybutyrate (βHB), are gaining importance, as they serve as both metabolic biomarkers and alternative energy sources in periods of low carbohydrate availability. In individuals with insulin resistance or prediabetes, cerebral glucose utilization is often impaired; leading to the use of ketone bodies as a compensatory energy source for the brain. Findings indicate that the individual ketone response to dietary interventions varies significantly between individuals and could thus itself be relevant as a metabolic phenotype marker in the context of precision nutrition. Therefore, the study also aims to further investigate the extent to which exogenous βHB supplementation influences neurocognitive processes and decision-making behavior, and whether characteristic neurocognitive phenotypes can be derived from this in metabolic risk groups.
This study will achieve its aims by completing a comprehensive lifestyle characterization and metabolic, molecular and neurocognitive phenotyping of individuals with different glycemic status (prediabetes, type 2 diabetes \[T2D\], and absence of prediabetes or T2D) in a German cohort. The study consists of modules A and B.
This record represents a description of module A which includes a 14-days observational period at home and two visits (screening and phenotyping visits) of the study center at the German Institute for Human Nutrition Potsdam-Rehbrueke before and after the observational period, respectively. In the observation period, food intake, sleep, activity, and interstitial glucose will be monitored during 14 days, and test meals will be consumed at two days at specific times. Study visits of module A include the intensive characterization using questionaries, anthropometric and metabolic assessments as well as collection of biosamples.
Module B has an interventional crossover design and is registered an a separate record. Module B takes place 1-12 weeks after module A and include two visits of the study center at the Free University of Berlin, separated by a two-week interval. Study visits of module B will focus on neurocognitive phenotyping including MRI of brain anatomy, function and complete computer-based decision-making behavior tests, and a consumption of the test drink containing ketone β-hydroxybutyrate (βHB) (test and placebo visits).
The aims of the study are as follows:
Primary aims:
- Identification of metabolic biomarkers and omics-based scores that predict individual glycemic response to food
- Identification of general lifestyle patterns that distinguish individuals with prediabetes or T2D from those without prediabetes or T2D
- Identification of personal factors and differences in lifestyle patterns that predict individual glucose response to food
Secondary aim:
• Elucidation of neuronal, metabolic, and molecular mechanisms associated with specific lifestyle patterns
Eligibility
Inclusion Criteria:
- Overweight or obesity (BMI 25-40 kg/m²)
- Good knowledge of German
Exclusion Criteria:
- Weight changes of more than 5% in the last 3 months
- Night shift work
- Travel across more than one time zone in the last month before and during study participation
- Intensive regular physical activity of more than 2 hours per day
- Current pregnancy or breastfeeding
- Severe renal, liver or heart disease
- Existing or past hematological malignancies, other malignant tumors, unless successfully treated more than 12 months before study start
- Severe neurological or psychiatric disorders
- Daily alcohol consumption of more than 20 grams or more than 150 grams per week
- Use of illicit or legal drugs one week prior to study start and during study participation
- Known systemic infections
- Type 1 diabetes and rare forms of diabetes
- Diabetes treatment with insulin or sulfonylureas or diabetes medication in the absence of manifest type 2 diabetes
- Unstable thyroid dysfunction
- Blood coagulation disorders or anticoagulation therapy that cannot be interrupted
- Medications affecting nutrient absorption
- Medications with immunosuppressants or steroids (oral or parenteral)
- Current eating disorders, functional or structural digestive disorders or bariatric surgery
- Food allergies or intolerances to ingredients of the test meals
- Intermittent fasting or calorie-restricted diet four weeks prior to the start of the study or during the study
- Ketogenic diet or ketogenic supplements four weeks prior to or during module B
- Left-handedness
- Severe claustrophobia
- Electrical implants or non-removable metallic implants
- Concurrent participation in another intervention study
- Assessment by the study physician based on medical concerns precluding study participation
