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To compare the vascular and metabolic effects of fatty acid blends containing plant-derived and marine-derived n-3 fatty acids in adults with type 2 diabetes, and to test whether their inclusion in a meal altered the postprandial effects of oleic acid.

• diagnosis of type 2 diabetes
• HbA1c < 9%
• treated with diet or oral hypoglycemic agents only

• fasting glucose > 16.7 mmol/l
• triacyglycerols > 4.5 mmol/l
• systolic blood pressure greater-than-or-equal-to 160 mmHg
• diastolic blood pressure greater-than-or-equal-to 95mmHg
• BMI > 35
• current smoker
• history of current diagnosis of cardiovascular disease
• diabetic retinopathy, neuropathy, or nephropathy
• use of medications or supplement known to affect lipids or blood pressure

 

Recruitment:  not specified

Design

• randomized, double-blind, three-phase cross-over design used
• treatment sessions separated by 7 days
• isocaloric test meals given and consumed within 15 minutes;
• flow-mediated dilation of the brachial artery assessed under fasting condition and again 4 hours after each meal
• blood samples collected after a 12-hour fast and 2 hours and 4 hours after each meal

Blinding used (if applicable): meal consisted of a beverage served in an unmarked container, with flavors and colors added to mask fat characteristics

Intervention (if applicable)

• 3 test meals
  • MUFA: 
    • 47% MUFA, 6.5% SFA, 14.1 % PUFA, 0.8% n-3
    • fat source 90% high-oleic safflower oil and 10% canola oil
    • 0.5 g alpha linoleic acid (ALA)
  • ALA + MUFA: 
    • 44.9% MUFA, 5.0% SFA, 18.4% PUFA, 4.8% n-3
    • fat source 70% canola oil, 20% high oleic safflower oil, 10% safflower oil
    • 3.3 g ALA
  • EPA/DHA + MUFA:
    • 44.2% MUFA, 7.0% SFA, 17% PUFA, 6.9% n-3
    • 60% high oleic safflower oil, 25% safflower oil, 15% sardine oil
    • 2.8 g EPA, 1.2g DHA, and 0.2 g ALA
• all meals were 13% protein from skimmed milk; 15% carbohydrate from skimmed milk, and 70% fat

Statistical Analysis

• all variables analysed using a mixed models approach
• models included treatment, time, and visit number as fixed effects and subject as a random effect
• there were no significant effects of treatment order and when significant effects of time were found the effect of treatment on change scores was examined
• Tukey-Kramer adjusted p values were used to examine the source of significant effects
• all analyses of FMD and blood flow were adjusted for basal means±SE
• interrelationships between the variables were estimated by partial Pearson correlation coefficients

 

Timing of Measurements:  see intervention above

Dependent Variables

• brachial arterial diameter and flow velocity, using duplex ultrasound imaging
• flow-mediated dilation(FMD)
• serum lipids
• blood glucose
• serum insulin
• insulin resistance and sensitivity

Independent Variables

•  composition of test meals

Control Variables

• fasting triacyglycerol levels

 

Initial N: 18 patients; 13 men, 5 women

Attrition (final N): 18

Age: 55.1±2.1 y

Ethnicity: not specified

Other relevant demographics: 17 had been diagnosed in the last 6 years and 16 were taking oral hypoglycemic dugs

Anthropometrics

• BMI 29.2±0.8

 Location: United States

 

Predictors of fasting flow-mediated dilation (FMD)

Lower fasting FMD was associated with increasing age (r=-0.72, p=0.001) and higher systolic blood pressure (r=-0.50, p=0.04).  There was no relationship between fasting FMD and insulin, glucose, or markers of insulin sensitivity or resistance.

Vascular and metabolic effects of fatty acid blends

Regardless of the fatty acid composition of the test meals, average FMD increased by 17% at 4 h, relative to the fasting baseline (average FMD=5.16±0.51 vs. 6.04±0.51 at 0 vs. 4 h, respectively, p=0.01).

Triacylglycerols significantly increased after each meal and the largest change was observed at 4 h after the meal.  Insulin concentrations increased 92% at 2 h (p<0.05) and returned to baseline at 4 h.  Glucose was significantly lower at 4 h postmeal vs. fasting levels (p<0.001).

Predictors of postprandial change in FMD

During the MUFA meal only, there was a significant inverse correlation between change in triacylglycerols and change in FMD (r=-0.50, P<0.05), such that subjects with the largest triacylglycerol increases after the MUFA meal exhibited reductions in endothelium-dependent vasodilation.  The opposite pattern was observed when test meals included 3 to 4 g of n-3 fatty acids.

Group differences in postprandial responses to the meals

During the MUFA treatment, the post-prandial triacylglycerols change (increase) was larger in the high triacyglycerols group than in the low group (p=0.01).  However the two groups did not differ when test meals included ALA or EPA/DHA, and there was no significant group-treatment interaction for triacylglycerols change (p<0.05). 

Following the MUFA meal there were no significant changes in FMD in either group.  When test meals included n-3 fatty acids, the high triacylglycerols showed significant increases in FMD at 4 h (P<0.04).  This response resulted in a significant treatment-group interaction for FMD change (P<0.03).

 Other Findings

When basal artery diameter was used as a covariate, fasting FMD was significantly lower in the high triacylglycerols group (p=0.03).

 

A meal containing 50g of fat, primarily from unsaturated fatty acids, was not associated with impaired endothelial fuction.

In patients with type 2 diabetes and high fasting triacylglycerols levels, meals containing 3 to 5 g of either plant- or marine-derived n-3 fatty acids actually significantly improved postprandial lipemia and endothelial function.

The data support the view that the vascular efects of a meal are dependent both on the fatty acid composition of the meal and the metabolic status of the subject.

The results suggest that adjunctive treatment with n-3 fatty acids could enhance endothelial function even in patients who are already taking hypoglycemic drugs.

Findings based on consumption of 1 meal.