NUtriGenomic Analysis in Twins (NUGAT)

Genetic Determinants of Metabolic Responses to Isocaloric Carbohydrate and Fat Diet Strategies

This is an intervention study in healthy adult twins with the aim to investigate the genetic determination of metabolic responses towards an isocaloric high carbohydrate, low fat diet versus an isocaloric low carbohydrate, high fat diet.

Study Overview

• Status: Completed
• Conditions: Metabolic Response to Dietary Modification
• Intervention / Treatment: Other: Isocaloric high carbohydrate diet intervention; Other: Isocaloric high fat diet intervention

Detailed Description

The impact of carbohydrates, proteins and fatty acids as major components of daily nutrition on the development of metabolic illnesses is an objective of numerous clinical studies. However, the effect of an isocaloric diet on metabolism is less investigated and not well understood. This study aims to reveal genetic determinated metabolic responses to an isocaloric high carbohydrate, low fat diet versus an isocaloric low carbohydrate, high fat diet in healthy twins. This study generates information for further detailed nutrigenomic analysis. Twins receive an isocaloric diet rich in carbohydrates (55% carbohydrates, 15% protein, 30% fat) with dietary counselling for 5 weeks and afterwards with nutrients supplied for 6 days, followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 15% protein, 45% fat) for 6 days with nutrients supplied and for 4 weeks with dietary counselling and again followed by another 6 days when nutrients were supplied. Anthropometry, blood tests and energy expenditure are performed after the period of diet rich in carbohydrates (Carb), after the first 6 days (HFshort) and at the end of the period of diet rich in fat (HFlong).

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Nuthetal
    • Potsdam-Rehbruecke, Nuthetal, Germany, 14558
      • German Institute of Human Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy twins
• BMI 18,5-35kg/m²
• BMI difference < 3kg/m² within the pair of twins
• Stable weight during the last 3 months
• Willingness to comply with the assigned diets over the study period

Exclusion Criteria:

• Consumptive diseases
• Intake of metabolic influence a/o anticoagulent drugs (e.g. cortisone, ASS, antibiotics)
• Diabetes type 1 and type 2
• Pregnancy
• Chronic disease of heart, kidney, liver
• High grade anaemia
• High grade infection disease
• Relevant change of body weight(+/- 2kg)during isoenergetic 12-weeks of dietary intervention
• Missing data about primary outcome measures (IVGTT, MTT, data about dietary intake from food diaries or food protocols)
• Significant deviation from dietary targets during the monitored 12 weeks isoenergetic period
• Allergies including food allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Diet interventions; Sequential dietary intervention	Other: Isocaloric high carbohydrate diet intervention; Time of 6 week, the last 6 days are standardized; Other: Isocaloric high fat diet intervention; Time of 6 weeks; the first and the last 6 days are standardized

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic variance of change in insulin secretion and sensitivity after sequential diets	change in insulin secretion and sensitivity measured with an intravenous glucose tolerance test (IVGTT)	6,7,12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variance of insulin sensitivity after the sequential diets	change in insulin sensitivity measured with a meal tolerance test (MTT) allowing for the response of the intestinal hormones	6, 7, 12 weeks
Expression of inflammatory markers in blood and fat tissue	Measurement of gene expression of inflammation cytokines and clock genes	6,7,12 weeks
Development of indices for the prediction of fat mass	Change of fat fraction in liver, abdominal and in the total body fat measuring by MRI/H1-spectroscopy, DEXA	6,7,12 weeks
Changes in vessel wall thickness of the carotid artery	Vascular ultrasound	6,7,12 weeks
Measurement of activity	each over 6 days measurement: activity protocol, pedometer and activity clock	in the 6th, 7th, 12th week
Detection of the gastric emptying time		6,7,12 weeks
Assessment of cognitive performance		0,5,11 weeks
Nutritional and genetic influence on the circadian rhythm	measurement of hormones in saliva and urine and of circadian gene expression in monocytes and PBMCs	6, 7, 12 weeks
Epigenetic modification of DNA	Change in adipose tissue DNA methylation pattern	6,7,12 weeks
Biometric data	Nutritional impact of the blood pressure, weight, body mass index, waist-hip ratio	6,7,12 weeks

Collaborators and Investigators

• Sponsor: German Institute of Human Nutrition
• Collaborators: Charite University, Berlin, Germany; University of Southern California; German Federal Ministry of Education and Research; Ludwig-Maximilians - University of Munich; Heidelberg University; University Hospital Tuebingen; Ernst von Bergmann Hospital; HealthTwist GmbH, Berlin, Germany; Max-Planck Institute of Molecular Cell Biology and Genetics; Helmholtz Center Munich
• Investigators: Principal Investigator: Andreas FH Pfeiffer, Prof, German Institute of Human Nutrition Potsdam-Rehbruecke

Publications and helpful links

General Publications

• Schuler R, Seebeck N, Osterhoff MA, Witte V, Floel A, Busjahn A, Jais A, Bruning JC, Frahnow T, Kabisch S, Pivovarova O, Hornemann S, Kruse M, Pfeiffer AFH. VEGF and GLUT1 are highly heritable, inversely correlated and affected by dietary fat intake: Consequences for cognitive function in humans. Mol Metab. 2018 May;11:129-136. doi: 10.1016/j.molmet.2018.02.004. Epub 2018 Feb 12.
• Schuler R, Osterhoff MA, Frahnow T, Seltmann AC, Busjahn A, Kabisch S, Xu L, Mosig AS, Spranger J, Mohlig M, Hornemann S, Kruse M, Pfeiffer AF. High-Saturated-Fat Diet Increases Circulating Angiotensin-Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient-Dependent Increases of Blood Pressure. J Am Heart Assoc. 2017 Jan 17;6(1):e004465. doi: 10.1161/JAHA.116.004465.
• Pivovarova O, Jurchott K, Rudovich N, Hornemann S, Ye L, Mockel S, Murahovschi V, Kessler K, Seltmann AC, Maser-Gluth C, Mazuch J, Kruse M, Busjahn A, Kramer A, Pfeiffer AF. Changes of Dietary Fat and Carbohydrate Content Alter Central and Peripheral Clock in Humans. J Clin Endocrinol Metab. 2015 Jun;100(6):2291-302. doi: 10.1210/jc.2014-3868. Epub 2015 Mar 30.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: June 1, 2012
• First Submitted That Met QC Criteria: June 27, 2012
• First Posted (Estimate): June 28, 2012

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Isocaloric; Nutrigenomics; Twins; High carbohydrat diet; High fat diet
• Other Study ID Numbers: BMBF NUGAT 0315424