PROTeIn-rich Meals to Control Glucose (PROTIME)

Meal Timing-based Strategies to Improve Glucose Metabolism in Prediabetes and Type 2 Diabetes

The overall aim is to identify the dietary pattern for prevention and treatment of type 2 diabetes. The specific aim of this pilot project is to compare effects of two diets with different diurnal distribution of carbohydrates and protein on the glucose metabolism in subjects with prediabetes and type 2 diabetes and its effects on inflammatory status.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Overweight; Type 2 Diabetes; Prediabetes
• Intervention / Treatment: Other: Diet with specific macronutrient composition.

Detailed Description

Overweight individual with prediabetes and non-insulin treated type 2 diabetes will be recruited for the study. The trial will have a cross-over design and compare metabolic effects of two isocaloric 4-week interventions with opposite timely distribution of macronutrient intake - a high-protein (HP) breakfast and a high-carb (HC) dinner (HP/HC intervention) vs. a HC breakfast and a HP dinner (HC/HP intervention) - divided by a 4-week wash-out phase. A HP low-carb meal (breakfast or dinner) will contain 35%E protein, 35%E carbs, and 30%E fat, and a HC meal (breakfast or dinner) will contain 10E%protein, 60%E carbs, and 30%E fat.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olga Ramich, PD Dr.; Phone Number: +4933200882749; Email: olga.ramich@dife.de
• Study Contact Backup: Name: Marina D´Urso; Phone Number: +4933200882690; Email: marina.durso@dife.de

Study Locations

• Germany
  • Potsdam-Rehbrücke
    • Potsdam, Potsdam-Rehbrücke, Germany, 14558
      • Recruiting
      • Olga Ramich
      • Contact: Olga Ramich, PD Dr.; Phone Number: +4933200882749; Email: olga.ramich@dife.de
      • Contact: Marina D'Urso; Phone Number: +4933200882690; Email: marina.durso@dife.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prediabetes (fasting blood sugar 100-125 mg/dl)
• Diabetes type 2 (fasting blood sugar >126 mg/dl)
• Overweight and obesity (BMI 25-50 kg/m2)

Exclusion Criteria:

• Other diabetes types
• Insulin treatment
• Shift work
• Weight changes >5% within past 3 months
• Systemic glucocorticoid therapy
• Systemic infections
• Severe anemia
• High blood pressure (>180/110 mmHg)
• Endocrinologic, liver and heart disorders
• Immune diseases
• Thyroid dysfunction
• Heart attack or stroke
• Cancer in the last 2 years
• Eating disorders, food intolerance/allergy, addiction disorders, digestive disorders intestinal, liver, cardiovascular diseases
• Hereditary or acquired coagulation disorders
• Non-interruptible intake of blood thinners (anticoagulants)
• Specific diets, intermittent fasting
• Pregnancy or breastfeeding
• Severe internal or psychiatric disorders or other conditions and drugs therapy that might influence the outcome of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HP/HC - HC/HP; Isocaloric 4-week HP/HC intervention followed by a 4-week HC/HP intervention.	Other: Diet with specific macronutrient composition.; The intervention is about an isocaloric diet that differs in terms of distribution of carbohydrates and protein throughout the day. The interventions include a HP-breakfast and a HC-dinner vs. a HC-breakfast and a HP-dinner. A HP low-carb meal (breakfast or dinner) will contain 35%E protein, 35%E carbs, and 30%E fat, and a HC meal (breakfast or dinner) will contain 10%E protein, 60%E carbs, and 30%E fat.
Experimental: HC/HP - HP/HC; Isocaloric 4-week HC/HP intervention followed by a 4-week HP/HC intervention.	Other: Diet with specific macronutrient composition.; The intervention is about an isocaloric diet that differs in terms of distribution of carbohydrates and protein throughout the day. The interventions include a HP-breakfast and a HC-dinner vs. a HC-breakfast and a HP-dinner. A HP low-carb meal (breakfast or dinner) will contain 35%E protein, 35%E carbs, and 30%E fat, and a HC meal (breakfast or dinner) will contain 10%E protein, 60%E carbs, and 30%E fat.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 24-hour glucose	Mean 24-hour glucose assessed by continuous glucose monitoring (CGM)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of height	Height measured by stadiometer	4 weeks
Measurement of body weight	Body weight measured by body scale	4 weeks
Waist and hip circumference / waist to hip ratio	Waist and hip circumference measured by tape measure	4 weeks
Systolic and diastolic blood pressure	Systolic and diastolic blood pressure changes measurement by manometer	4 weeks
Body fat and lean mass	Body fat and lean mass assessed by bioelectrical impendance analysis (BIA)	4 weeks
Energy expenditure and substrate oxidation rates	Energy expenditure and substrate oxidation rates assessed by indirect calorimetry	4 weeks
Hepatic values (gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT))	GGT, AST, ALT etermined in fasting blood samples	4 weeks
Renal values (creatinine, urea, uric acid)	Renal values determined in fasting blood samples	4 weeks
Intra- und inter-day glycemic variability	Indices of intra- and inter-day glycemic variability assessed by continuous glucose monitoring (CGM)	4 weeks
Glucose levels in meal tolerance test (MTT)	Glucose levels in blood samples collected in MTT	4 weeks
Metabolic hormones (insulin, C-peptide, glucagon, glucagon-like peptite 1(GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, adiponectin, leptin)	Blood levels of metabolic hormones assessed in fasting state and during the MTT	4 weeks
Inflammatory markers and T cell populations analyses	Level of the inflammatory markers IL-6, TNFa, MCP-1 and T cell populations in circulation and adipose tissue are assessed through blood analysis and fat biopsy	4 weeks
Satiety and hunger scores	Satiety and hunger scores assessed using Visual Analog Scale (VAS with a scale of 1-100, where higher values correspond to stronger satiety/hunger)	4 weeks
Sleep/wake timing and sleep quality	Sleep/wake timing and sleep quality 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	4 weeks
Physical activity	24-h physical activity will be monitored by an ActiGraph device	4 weeks
Adipose tissue transcriptome	RNA-Seq analysis of subcutaneous adipose tissue sample	4 weeks
Gene expression in peripheral blood mononuclear cells (PBMC)	Expression of metabolic genes assessed by qPCR	4 weeks
Gut microbiota and microbiome-derived metabolites	Determined in stool samples and blood plasma	4 weeks
Determination of decision behavior	Impulsiveness assessed by decision making tasks on computer	4 weeks

Collaborators and Investigators

• Sponsor: German Institute of Human Nutrition
• Collaborators: Charite University, Berlin, Germany; Helmholtz Center Munich; Hasso Plattner Institute, Potsdam, Germany
• Investigators: Principal Investigator: Olga Ramich, PD Dr., German Institute of Human Nutrition

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: April 21, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Prediabetes; Overweight; Type 2 Diabetes; Glucose; Metabolism; Chrononutrition; High-protein; Macronutrient composition; High-carb; Isocaloric diet; Prevention and treatment of type 2 diabetes
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; Prediabetic State; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet
• Other Study ID Numbers: 90/2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No