Randomized Controlled Trial

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To examine the relationship between serum lipid fatty acids and glucose metabolism (glucose tolerance) before and after the consumption of a diet enriched in either monounsaturated (Mono diet) or polyunsaturated (Poly diet) fatty acids.

Subjects had to have impaired glucose tolerance in two consecutive oral glucose tolerance tests according to World Health Organization criteria.

• History of thyroid, kidney or liver disease
• Previously diagnosed with diabetes
• Taking lipid-lowering medication.

Recruitment

Recruitment was reported previously in the literature.

Design

• Randomized clinical trial
• All subjects consumed a run-in diet for three weeks initially before the start of the study. After this three-week period, subjects were randomly assigned into either the Mono or Poly diet for eight weeks. Subjects visited the research unit at minus-three weeks (the start of the run-in diet); week zero (baseline); and at two, four and eight weeks.

Intervention

• The run-in diet was followed by all subjects for the initial three weeks of the study. Diet composition was 37% of energy as fat:
  • 18% saturated
  • 11% monounsaturated
  • 5% polyunsaturated fat
• After the run-in diet period, subjects were randomly assigned into either the Poly or Mono diet for eight weeks. The fatty acid composition was altered with the use of different kinds of spreads, oils and salad dressings. Dietary compliance was monitored by repeated four-day food records kept before study visits.
• The Poly diet: 34% of energy as fat; 11% saturated, 10% monounsaturated and 10% polyunsaturated
• The Mono diet: Considered high-fat with 40% of total energy as fat; 11% saturated, 19% monounsaturated and 8% as polyunsaturated.

Statistical Analysis

• Normal distribution of the fatty acids in different serum lipid fractions (saturated, mono, n-6, n-3) were tested with the Shapiro-Wilk's test and found to not be normally distributed. After mathematical transformations, they did not become normally distributed and thus non-parametric tests were used with all analysis. 
• Mann-Whitney U-test was used to analyze differences in the means and in the absolute and percentage changes (from zero to eight weeks) between the two diet groups
• Wilcoxon's matched-pairs signed-rank test was used to analyze the within-group changes in dietary intake
• Spearman correlation coefficients were calculated between selected variables
• To analyze if outliers affected the strength of associations presented, the correlation coefficients were calculated with and without outliers. The exclusion of outliers did not affect the association.
• P<0.05 was considered significant.

Timing of Measurements

• Subjects came to the research unit at three weeks prior to the start; week zero (baseline); and weeks two, four and eight
• Dietary data was collected via four-day food records repeated three times during the eight-week study period. The run-in diet was consumed for the initial three weeks (weeks minus-three to baseline week zero) and the Mono or Poly diet was initiated at week zero to follow until week eight.

Dependent Variables

• Insulin Sensitivity Index (S₁): Measures the ability of the increase in plasma insulin to enhance glucose's ability to accelerate its net disappearance from plasma.plasma insulin
• Glucose Effectiveness (S_G): Measured with a glucose oxides method, it is a measure of the ability of glucose to enhance its own disappearance from plasma at the baseline insulin concentration
• The acute insulin response: Measured with a frequently sampled IV glucose tolerance test that was determined at baseline and eight weeks. Calculated by using the area under the insulin response curve above the baseline value from zero to 10 minutes.
• Fatty acid profile of serum cholesteryl esters, triacylglycerols and phospholipids: Determined at baseline and eight weeks.

Independent Variables

• The Mono or Poly diet
• All subjects completed four-day food records at three different times during the study to ensure that they were following the appropriate diet and there were no significant differences between groups.

Control Variables

All subjects continued their medications throughout the study without any change.

• Initial N: 31 subjects; 13 women, 18 men
• Attrition (final N): 31 subjects; 14 in the Mono diet, 17 in the Poly diet. Attrition was not discussed in this article as recruitment details were discussed in previously published literature.
• Age: 56±5 years
• Ethnicity: Not specified in this article; however, the study took place in Finland.
• Location: Finland.

Findings

• Fatty acid profile:
  • Oleic and α-linolenic acids increased significantly more after consumption of the Mono diet
  • Proportion of linoleic acid in serum triacylglycerol and cholesteryl ester fractions increased more after consumption of the Poly diet
  • In the phospholipid fraction: The proportion of oleic acid decreased after consumption of both diets, but the decrease was more significant in the Poly diet. The proportion of α-linolenic acid increased after the Mono diet. Linoleic acid increased after consumption of the Poly diet.
  • The proportion of eicosapentaenoid acid in the cholesteryl ester and phospholipid fractions increased in the Mono group, and decreased in the Poly diet group.
• IV glucose tolerance test:
  • No significant difference were found in the variables of glucose metabolism between the two diet groups
  • There was a tendency toward a greater reduction in fasting plasma glucose in the Mono group than in the Poly group (P=0.053)
  • S_G was higher in the Mono diet group than in the Poly diet group (P=0.013)
• Fatty acid profile of serum lipids and indexes of glucose and insulin metabolism:
  • A higher S_G at baseline was associated with higher proportions of oleic and α-linolenic acids in phospholipids
  • A higher S_I at baseline was associated with a lower proportion of saturated fatty acids in triacylglycerols
  • S_I tended to be higher in subjects with higher proportions of docosapentaenoic acid in the triacylglycerol fraction (P=0.09), and of docosahexaenoic acid in both the triacylglycerol (P=0.09) and cholesteryl ester fractions.

Fasting Plasma Glucose and Insulin, Acute Insulin Response (AIR: Zero to 10 Minutes), Insulin Sensitivity (S_I), and Glucose Effectiveness (S_G) in the High-fat Mono Diet and Reduced Fat Poly Diet Groups in the Study.¹

 

	Diet Group		Diet Group
	Mono Diet		Poly Diet
Fatty Acid	Zero Weeks	Change Zero to Eight Weeks	Zero Week	Change Zero to Eight Weeks
Plasma glucose (mmol per L)	6.4±1.2	-0.9±1.1	6.3±0.7	-0.3±0.82
Plasma insulin (mU per L)	15.9±8.1	-5.5±7.7	14.3±7.2	-4.4±9.3
AIR (mU per L•min)	117±243	60±128	137±263	-29±123
SI (x 10-4min-1•μU-1•mL-1)	1.37±0.78	0.33±0.93	1.90±1.04	0.06±0.56
SG(min-1 x 102)	1.36±0.53	0.27±0.65	1.14±0.65	0.02±0.51

¹ Mean ± SD.

 ² Significantly different from the Mono diet, P=0.053 (Mann-Whitney U-test).   

Other Findings

• An increase in the proportion of oleic and α-linolenic acids in phospholipids was associated with a decrease in the fasting plasma glucose concentration
• An increase in the S_G was associated with an increase in the proportion of oleic acid and with a decrease in the proportion of arachidonic acid in phospholipids.

Beneficial changes in the S_G and the fasting plasma glucose during the Mono diet were associated with alteration in the proportions of oleic, α-linolenic, and arachidonic acids in phospholipids. It is possible that a larger difference would have been seen if the Mono diet was lower in overall dietary fat.

Government:	Council for Health Sciences, Academy of Finland; the Ministry of Education, Finland
Industry:	Van den Bergh Foods; Valio Ltd, Finland. Food Company:
Not-for-profit	Foundation for Nutrition Research, Helsinki Other non-profit:

Small numbers of subjects in groups.