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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
12
Laval University
Québec, Quebec, Canada
Change in the in vivo kinetics of intestinally derived apoB-48-containing lipoproteins between the two 8-week interventions
Time frame: At the end of the two 8-week interventions
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
Time frame: 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
Time frame: At the end of the two 8-week interventions
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