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

NCT01449773 | Completed

• 1 other identifier: INAF-117.05.01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (2)

n-3 PUFAs

EXPERIMENTAL

Dietary Supplement: n-3 PUFAs

Corn and soybean oil pill

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

n-3 PUFAs DIETARY_SUPPLEMENT

5 capsules/day in order to provide 3 g/day of n-3 PUFAs.

n-3 PUFAs

Placebo DIETARY_SUPPLEMENT

5 capsules/day containing corn and soybean oil

Corn and soybean oil pill

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Laval University: lead

Study Sites (1)

Laval University

Québec, Quebec, G1V 0A6, Canada

Location

Related Publications (1)

• 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.

  PMID: 23855973 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Patrick Couture, MD, PhD, FRCP

  Laval University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 10, 2011
• Study Start: April 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: January 1, 2013
• Last Updated: March 4, 2013

Record last verified: 2013-02

Locations

CA (1)