Effects of N-3 Polyunsaturated Fatty Acids On Chylomicron Secretion And Expression Of Genes That Regulate Intestinal Lipid Metabolism In Men With Type 2 Diabetes (DBB48)

The overaccumulation of apoB-48-containing lipoproteins of intestinal origin seen in patients with type 2 diabetes are now thought to be attributable to elevated intestinal production and reduced clearance. Substantial evidence exists indicating that elevated plasma levels of these lipoproteins are associated with increased cardiovascular disease risk. Therefore, reduction of atherogenic plasma triglyceride-rich lipoproteins (TRL) levels of intestinal origin appears to be crucial to improve CVD risk associated with type 2 diabetes. In this regard, n-3 PUFAs have been shown to exert beneficial effects on diabetic dyslipidemia. However, the investigators understanding of the physiological changes that occur with n-3 PUFA supplementation is suboptimal, thereby limiting the investigators appreciation of its impact on CVD risk associated with type 2 diabetes. The effects of n-3 PUFAs on the intestinal production of TRLs and the expression of genes regulating intestinal lipid absorption and chylomicron synthesis have not yet been examined in humans. The general objective of the proposed research is to investigate the mechanisms by which n-3 PUFAs beneficially modify intestinal lipoprotein metabolism in patients with type 2 diabetes. The investigators hypothesize that n-3 PUFA supplementation in men with type 2 diabetes will:

• reduce TRL apoB-48 production rate and increase fractional catabolic rate of these lipoproteins,
• decrease the expression of genes that regulate intestinal lipid absorption and synthesis as well as synthesis of apoB-48-containing lipoproteins,
• decrease both plasma surrogates of cholesterol absorption and cholesterol synthesis.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Dietary supplement: n-3 PUFAs; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 0A6
    • Laval University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• age between 18 and 55 years,
• plasma TG levels above the 50th percentile for age,
• non-smoker,
• BMI between 25.0 and 40.0 kg/m2,
• stable body weight for at least 6 months prior to the study baseline,
• HbA1c between 6.5 and 8.5%,
• baseline fasting plasma glucose < 15.0 mmol/L
• patients with de novo type 2 diabetes not taking oral hypoglycemic agents -- - or patients having received stable doses of metformin for at least 3 months before randomization.

Exclusion Criteria:

• extreme dyslipidemias such as familial hypercholesterolemia,
• patients with secondary form of diabetes or acute metabolic diabetic complications,
• patients having received or being treated with insulin or a thiazolidinedione within the past 6 months,
• subjects having CVD (CHD, cerebrovascular disease or peripheral arterial disease)
• subjects taking medications known to affect lipoprotein metabolism (e.g. steroids, beta blockers, thiazide diuretics, lipid lowering agents,
• significant alcohol intake

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: n-3 PUFAs	Dietary supplement: n-3 PUFAs; 5 capsules/day in order to provide 3 g/day of n-3 PUFAs.
Placebo Comparator: Corn and soybean oil pill	Dietary supplement: Placebo; 5 capsules/day containing corn and soybean oil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in the in vivo kinetics of intestinally derived apoB-48-containing lipoproteins between the two 8-week interventions	At the end of the two 8-week interventions

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in the expression of genes that regulate intestinal lipid absorption (NPC1L1, ABCG5/8, FABP, SREBP-1c) and synthesis (DGAT, ACAT2, HMG CoA reductase) as well as synthesis of apoB-48-containing lipoproteins (MTP)between the two 8-week interventions	At the end of the two 8-week interventions
Change in the plasma surrogates of cholesterol absorption (campesterol, beta-sitosterol) and synthesis (lathosterol) between the two 8-week interventions	At the end of the two 8-week interventions

Collaborators and Investigators

• Sponsor: Laval University
• Investigators: Principal Investigator: Patrick Couture, MD, PhD, FRCP, Laval University

Publications and helpful links

General Publications

• Labonte ME, Couture P, Tremblay AJ, Hogue JC, Lemelin V, Lamarche B. Eicosapentaenoic and docosahexaenoic acid supplementation and inflammatory gene expression in the duodenum of obese patients with type 2 diabetes. Nutr J. 2013 Jul 15;12:98. doi: 10.1186/1475-2891-12-98.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: October 6, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (Estimate): October 10, 2011

Study Record Updates

• Last Update Posted (Estimate): March 4, 2013
• Last Update Submitted That Met QC Criteria: February 28, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: INAF-117.05.01