Postprandial Inflammation and Fatty Acids (PIFA)

Effects of Fatty Acids on Postprandial Inflammatory Response of Healthy Obese and Type 2 Diabetic Obese Subjects

The main objective is to elucidate the acute effects of an oral intake of either saturated, monounsaturated or polyunsaturated fatty acids on peripheral blood mononuclear cells (PBMC) whole genome expression of obese and type 2 diabetic obese subjects.

Study Overview

• Status: Completed
• Conditions: Obesity; Cardiovascular Disease; Diabetes Type 2
• Intervention / Treatment: Other: High saturated fat shake; Other: High monounsaturated fat shake; Other: High polyunsaturated fat shake

Detailed Description

Consumption of high-fat diets can lead to postprandial dyslipidemia, impairment of endothelial function, activation of immune cells and changes in gene expression profiles of immune cells such as peripheral blood mononuclear cells (PBMC). Recently it was shown that postprandial gene expression profiles of PBMC and plasma triglyceride (TG) and free fatty acid (FFA) responses are dependent on the type of dietary fat consumed (i.e. saturated, monounsaturated and polyunsaturated). Since obese and diabetic subjects usually are in a pro-inflammatory state and have dyslipidemia and endothelial dysfunction we are interested in the effect of different fatty acids in a high load on the PBMC gene expression profiles, plasma cytokine profiles and endothelial function of these subjects.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Wageningen, Netherlands, 6700 EV
    • Wageningen University, Division of Human Nutrition
  • Gelderland
    • Wageningen, Gelderland, Netherlands, 6700 EV
      • Wageningen University, Division of Human Nutrition

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

For all participants:

• male gender
• 50-70 yrs

For diabetic patients only:

• BMI >30 kg/m2
• Well-controlled diabetes: fasting plasma glucose concentration must be <10.0 mmol/l at the time of screening.
• Must be on sulphonylurea- or metformin therapy for at least 6 months with a constant dose for at least two months, or on dietary treatment for at least 6 months2.

For obese controls only:

• BMI > 30 kg/m2
• normoglycemic according to WHO criteria (OGTT, fasting blood glucose< 7 mmol/L, after 2 hr <7.8mmol/L)

For lean controls only:

• BMI 18-25 kg/m2
• normoglycemic according to WHO criteria (OGTT, fasting blood glucose< 7 mmol/L, after 2 hr <7.8mmol/L)

Exclusion Criteria:

For all participants:

• Female gender
• Age below 50 or above 70 years
• Hemoglobin levels <8.4 mmol/L
• Allergic to cow milk or dairy products
• Allergic to fish oil
• Vegetarian
• Tobacco smoker
• Current or recent (<4 weeks) use of fish oil supplements or more then four times fish/week; 24.35 g of EPA-DHA of fish per month (800 mg/day) as judged by the questionnaire.
• Received inoculations within 2 months of starting the study or planned to during the study
• Donated or intended to donate blood from 2 months before the study till two months after the study
• Unstable body weight (weight gain or loss > 3 kg in the past three months)
• Medical condition that can interfere with the study outcome (i.e. cardiovascular disease, gastrointestinal disease, renal dysfunction)
• Use of medications know to interfere with glucose homeostasis (i.e. corticosteroids)
• abuse of drugs and/or alcohol
• participation in another biomedical study within 1 month before the first screening visit

For obese, type 2 diabetic subjects only:

• severe diabetes which requires application of insulin
• diabetes-related complications

For obese subjects and lean controls only:

• hyperglycemic according to WHO criteria (OGTT, fasting blood glucose >6.0mM, after 2 hr>11mM)
• systolic blood pressure >160 mmHg or diastolic blood pressure > 100 mmHg
• Urinary glucose concentrations (>0.25 g/l)

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy control subjects, High saturated fat shake	Other: High saturated fat shake; milkshake containing 95 gram of fat, high percentage of saturated fat
Experimental: Healthy control subjects, High Monounsaturated fat shake	Other: High monounsaturated fat shake; milkshake containing 95 gram of fat, high percentage of monounsaturated fat
Experimental: Healthy control subjects, High Polyunsaturated fat shake	Other: High polyunsaturated fat shake; milkshake containing 95 gram of fat, high percentage polyunsaturated fat
Experimental: Healthy obese subjecs, High saturated fat shake	Other: High saturated fat shake; milkshake containing 95 gram of fat, high percentage of saturated fat
Experimental: Healthy obese subjects, High monounsaturated fat shake	Other: High monounsaturated fat shake; milkshake containing 95 gram of fat, high percentage of monounsaturated fat
Experimental: Healthy obese subjects, High polyunsaturated fat shake	Other: High polyunsaturated fat shake; milkshake containing 95 gram of fat, high percentage polyunsaturated fat
Experimental: Obese diabetes type 2 subjects, High Saturated fat shake	Other: High saturated fat shake; milkshake containing 95 gram of fat, high percentage of saturated fat
Experimental: Obese diabetes type 2 subjects, High Monounsaturated fat shake	Other: High monounsaturated fat shake; milkshake containing 95 gram of fat, high percentage of monounsaturated fat
Experimental: Obese diabetes type 2 subjects, High polyunsaturated fat shake	Other: High polyunsaturated fat shake; milkshake containing 95 gram of fat, high percentage polyunsaturated fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PBMC gene expression profiles	0, 2, 4 hrs

Secondary Outcome Measures

Outcome Measure	Time Frame
PBMC inflammatory response capacity	0, 2, 4 hrs
Endothelial function	0, 2, 4 hrs

Collaborators and Investigators

• Sponsor: Wageningen University
• Collaborators: Dutch Diabetes Research Foundation
• Investigators: Study Chair: Michael Muller, Prof, Chair Department of human nutrition NMG group; Principal Investigator: Lydia A Afman, PhD, Senior scientist department Human Nutrition Wageningen University

Publications and helpful links

General Publications

• Esser D, van Dijk SJ, Oosterink E, Muller M, Afman LA. A high-fat SFA, MUFA, or n3 PUFA challenge affects the vascular response and initiates an activated state of cellular adherence in lean and obese middle-aged men. J Nutr. 2013 Jun;143(6):843-51. doi: 10.3945/jn.113.174540. Epub 2013 Apr 24.
• van Dijk SJ, Mensink M, Esser D, Feskens EJ, Muller M, Afman LA. Responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes: a randomized trial. PLoS One. 2012;7(7):e41388. doi: 10.1371/journal.pone.0041388. Epub 2012 Jul 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 14, 2009
• First Posted (Estimate): September 15, 2009

Study Record Updates

• Last Update Posted (Estimate): April 21, 2010
• Last Update Submitted That Met QC Criteria: April 20, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Keywords: inflammation; nutrigenomics; fatty acids; peripheral blood mononuclear cells
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Cardiovascular Diseases; Diabetes Mellitus, Type 2
• Other Study ID Numbers: NL2800108109