Obesity &Amp; Overweight, Prediabetes, Type 2 Diabetes
Conditions
Keywords
Time-restricted eating, Prediabetes, Type 2 Diabetes, Chrononutrition, Glucose metabolism, Overweight, Obesity, Continuous glucose monitoring, TRE, Prevention and treatment of type 2 diabetes
Brief summary
The objective of this study is to investigate the impact of hypocaloric time-restricted eating (TRE) at different day times (early versus late TRE) on glucose metabolism and other cardiometabolic parameters in individuals with overweight and with normal, or impaired glucose metabolism (prediabetes and type 2 diabetes). In addition, the study aims to elucidate the molecular mechanisms underlying these effects.
Detailed description
This dietary intervention study will follow a crossover design. During the intervention phases, participants will restrict their dietary intake to a defined eating window of 8 hours - predominantly in the morning (early TRE) or predominantly in the afternoon (late TRE) - in conjunction with a moderate caloric restriction for five weeks. A 10-12-week washout phase will separate the intervention periods. Overweight and obese individuals with healthy glucose metabolism, prediabetes, or non-insulin-treated type 2 diabetes will be recruited for the study.
Interventions
BEHAVIORALEarly Time-Restricted Eating
Participants will restrict their eating window (8 hours eating and 16 hours fasting per day) and caloric intake moderately. During the early TRE intervention, participants will primarily consume their meals in the morning. The precise eating window will be defined based on the individual chronotype of the participants. Additionally, participants will be required to reduce their daily caloric consumption by 25%. They will replace one daily meal with a calorie-reduced product to facilitate caloric restriction.
BEHAVIORALLate Time-Restricted Eating
Participants will restrict their eating window (8 hours eating and 16 hours fasting per day) and caloric intake moderately. During the late TRE intervention, participants will primarily consume their meals in the evening. The precise eating window will be defined based on the individual chronotype of the participants. Additionally, participants will be required to reduce their daily caloric consumption by 25%. They will replace one daily meal with a calorie-reduced product to facilitate caloric restriction.
Sponsors
Technische Universität Dresden, Germany
University of Surrey, UK
University of Geneva, Switzerland
Technische Universität München, Germany
German Diabetes Center (DDZ), Germany
University of Rovira i Virgili, Spain
German Institute of Human Nutrition
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Overweight or obesity (BMI 25-40 kg/m²) * Healthy glucose metabolism (fasting glucose \<100 mg/dl and glucose after 2 hours OGTT \<140 mg/dl) * OR impaired glucose metabolism (fasting glucose 100-125 mg/dl and/or glucose after 2 hours OGTT 140-199 mg/dl and/or HbA1c 5.7-6.4%) * OR type 2 diabetes (according to existing medical diagnosis or fasting glucose \>126 mg/dl and/or glucose after 2 hours OGTT \>200 mg/dl and/or HbA1c ≥6.5%) * Daily eating window ≥12 hours
Exclusion criteria
* Weight changes \> 5% within past 3 months * Shift work * Traveling across more than one time zone within one month prior to the study * Pregnancy and breastfeeding * Eating disorders, food intolerance/allergy to ingredients in the diet product, vegan diet, practicing time-restricted eating * Severe chronic illnesses or other conditions that are incompatible with the planned intervention and examination program (e.g. type 1 diabetes, recent cardiovascular event, malabsorption, cancer in the last two years, etc.) * Treatment with insulin, sulfonylureas, and GLP-1 receptor agonists, steroid use (oral, cutaneous, or parenteral), regular intake of melatonin, anticoagulation treatment that cannot be paused * Extreme early and extreme late chronotypes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean 24-hour glucose | 5 weeks | Mean 24-hour glucose assessed by continuous glucose monitoring (CGM) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gene expresssion in adipose tissue | 5 weeks | RNAseq analysis of subcutaneous adipose tissue samples |
| 3-nitrotyrosine | 5 weeks | Plasma 3-nitrotyrosine \[pmol/mg\] |
| Protein carbonyls | 5 weeks | Plasma protein carbonyls \[nmol/mg\] |
| 36-item Short Form Health Survey (SF-36) to measure health-related quality-of-life | 5 weeks | Health-related quality-of-life, as assessed by the 36-Item Short Form Health Survey (SF-36, with scores ranging from 0 to 100, with a higher score defining a more favorable health state) |
| Satisfaction with the intervention | 5 weeks | Satisfaction with the intervention assessed by a 5-point Likert scale (with 5 representing Very satisfied and 1 representing Very dissatisfied) |
| Decision behavior | 5 weeks | Impulsiveness assessed by decision making tasks on computer |
| Glycemic variability | 5 weeks | Inter- and intraday indices of glycemic variability assessed by CGM |
| Glucose levels | 5 weeks | Fasting and postprandial glucose \[mg/dL\] in response to a mixed meal tolerance test |
| Insulin levels | 5 weeks | Fasting and postprandial insulin \[mU/L\] in response to a mixed meal tolerance test |
| Glucagon levels | 5 weeks | Fasting and postprandial glucagon \[pmol/L\] in response to a mixed meal tolerance test |
| Insulin resistance | 5 weeks | Insulin resistance, as assessed by HOMA-IR \[AU\] |
| Insulin secretion | 5 weeks | Insulin secretion, as assessed with the insulinogenic index \[AU\] |
| Body weight | 5 weeks | Body weight \[kg\], as measured by scale weight |
| Body Mass Index (BMI) | 5 weeks | BMI \[kg/m2\], calculated as weight/square height |
| Waist and hip circumference | 5 weeks | Waist and hip circumference \[cm\] measured by tape |
| Body composition | 5 weeks | Body fat mass and lean mass \[kg\], as measured by bioelectrical impendance analysis (BIA) |
| Fasting cholesterol | 5 weeks | Fasting total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol \[mmol/L\] |
| Fasting triglycerides | 5 weeks | Fasting triglycerides \[mmol/L\] |
| Blood pressure | 5 weeks | Systolic and diastolic blood pressure \[mm Hg\], as measured by manometer |
| Resting energy expenditure | 5 weeks | Resting energy expenditure \[kcal/day\], as assessed by indirect calorimetry |
| Inflammatory markers in blood and adipose tissue | 5 weeks | Levels of adipokines and inflammatory markers measured in blood samples and subcutaneous adipose tissue samples |
| Subjective satiety and hunger sensation | 5 weeks | Satiety and hunger scores assessed using Visual Analog Scales (VAS, with a scale of 1-100, where higher values correspond to stronger satiety/hunger) |
| Concentration of satiety and hunger regulating hormones | 5 weeks | Levels of ghrelin and peptide YY (PYY), as measured in blood samples in \[pg/mL\] |
| Species and strain-level microbiome changes | 5 weeks | Species and strain-level microbiome changes, as assessed by 16S rRNA gene sequencing of stool samples |
| Levels of microbiome-derived metabolites | 5 weeks | Levels of microbiome-derived metabolites measured in stool samples and blood plasma |
| Sleep quality | 5 weeks | Sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI score, which ranges from 0-21, where higher values correspond to worse sleep quality) and also monitored by an ActiGraph device |
| Sleep and wake timing | 5 weeks | Sleep onset and offset assessed by the Pittsburgh Sleep Quality Index (PSQI score, which ranges from 0-21, where higher values correspond to worse sleep quality) and in addition by using a sleep diary |
| Internal circadian phase | Screening visit (week 0) | Internal circadian phase as assessed using the BodyTime assay in peripheral mononuclear blood cells (PBMCs) |
| Glucagon-like peptide-1 levels | 5 weeks | Fasting and postprandial glucagon-like peptide-1 (GLP-1) in response to a mixed meal tolerance test \[pM\] |
| Gastric inhibitory polypeptide | 5 weeks | Fasting and postprandial gastric inhibitory polypeptide (GIP) in response to a mixed meal tolerance test \[pg/mL\] |
| Gene expresssion in peripheral mononuclear blood cells (PBMCs) | 5 weeks | RNAseq analysis of clock, metabolic and inflammatory gene expression peripheral mononuclear blood cells (PBMCs) |
| Malondialdehyde | 5 weeks | Plasma malondialdehyde \[µmol/L\] |
Other
| Measure | Time frame | Description |
|---|---|---|
| Food intake | 5 weeks | Energy intake \[kcal/day\] assessed by food records |
| Macronutrient intake | 5 weeks | Percentage of calories from fat, carbohydrates, protein, and fiber, determined based on dietary records |
| Food timing | 5 weeks | Start and stop times of daily eating window and clock time of each daily meal intake assessed by food records |
| Physical activity level | 5 weeks | 24-h physical activity level (light, moderate, sedentary activity, metabolic equivalent of task) will be monitored by an Actigraph device |
| Liver enzyme levels and renal values | 5 weeks | γ-glutamyltransferase (GGT), aspartate aminotransferase (ALT), and alanine aminotransferase (AST), creatinine, urea, uric acid determined in fasting blood samples |
Countries
Germany
Contacts
Primary ContactOlga Ramich, Prof. Dr.
Backup ContactBettina Schuppelius, M.Sc.
Outcome results
None listed