PDM: Prediabetes (2013)


Louheranta AM, Sarkkinen ES, Vidgren HM, Schwab US, Uusitupa MIJ. Association of the fatty acid profile of serum lipids with glucose and insulin metabolism during two fat-modified diets in subjects with impaired glucose tolerance. Am J Clin Nutr. 2002; 76: 331-337. 

PubMed ID: 12145003
Study Design:
Randomized Controlled Trial
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Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

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.

Inclusion Criteria:

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

Exclusion Criteria:
  • History of thyroid, kidney or liver disease
  • Previously diagnosed with diabetes
  • Taking lipid-lowering medication.
Description of Study Protocol:


Recruitment was reported previously in the literature.


  • 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.


  • 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.
Data Collection Summary:

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 (SG): 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.

Description of Actual Data Sample:
  • 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.
Summary of Results:


  • 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)
    • SG 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 SG at baseline was associated with higher proportions of oleic and α-linolenic acids in phospholipids
    • A higher SI at baseline was associated with a lower proportion of saturated fatty acids in triacylglycerols
    • SI 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 (SI), and Glucose Effectiveness (SG) 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 SG was associated with an increase in the proportion of oleic acid and with a decrease in the proportion of arachidonic acid in phospholipids.
Author Conclusion:

Beneficial changes in the SG 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.

Funding Source:
Government: Council for Health Sciences, Academy of Finland; the Ministry of Education, Finland
Van den Bergh Foods; Valio Ltd, Finland.
Food Company:
Foundation for Nutrition Research, Helsinki
Other non-profit:
Reviewer Comments:

Small numbers of subjects in groups.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? No
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? ???
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? ???
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes