DFA: Linoleic Acid (LA) and Intermediate Health Outcomes (2011)

Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

Investigation of the associations of serum non-esterified and lipid-standardized esterified fatty acid composition, with the risk for developing DM or IFG over four years, in a population-based sample of middle-aged men from eastern Finland.

Inclusion Criteria:
  • Men living in eastern Finland and participating in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD)
  • 42, 48, 54 or 60 years old at baseline
  • Undergone carotid ultrasound examination in the original study
  • Non-diabetic and normoglycaemic at baseline
  • Results on serum fatty acid composition.
Exclusion Criteria:

Diabetes: Fasting blood glucose of at least 6.1mmol per L or a clinical diagnosis of DM with either dietary, oral or insulin treatment.

Description of Study Protocol:
  • Recruitment: No information given
  • Design: Prospective cohort
  • Blinding used: Assumed for laboratory analyses.
  • Intervention: Grouped by serum fatty acid composition.

 Statistical Analysis

  • The trend across the groups of men who remained normoglycaemic, developed IFG or developed DM during follow-up was assessed with linear regression and, where indicated, logistic regression
  • For assessment of serum fatty acid composition as a determinant of changes (absolute differences) in insulin and glucose concentration over the four-year follow-up, covariance analysis was used
  • Trends across fatty acid categories were assessed with multivariate regression and the effect of fatty acid categories was assessed with ANOVA
  • The association of serum fatty acid composition with the risk of developing DM or IFG in four years was estimated using logistic regression
  • Because the number of new cases of DM was small, cases of IFG and DM were pooled for multivariate logistic regression analyses
  • Indices of serum fatty acid composition were categorized into thirds for both logistic regression and covariate analyses, although results were similar using continuous variables
  • Significance was considered to be P<0.05.
Data Collection Summary:
  • Timing of measurements: Baseline and four-year follow-up
  • Dependent variables: Risk of developing diabetes; normoglycaemic, IFG, diabetes. Diabetes was defined as fasting blood glucose of at least 6.1 mmol per L or a clinical diagnosis of DM with either dietary, oral or insulin treatment. IFG was defined as fasting blood glucose of 5.6 mmol to 6.0 mmol per L.
  • Independent variables: Serum fatty acid composition.

Control Variables

  • Age
  • BMI
  • Use of anti-hypertensive medications
  • DBP
  • Smoking
  • Alcohol consumption
  • Concentrations of triglycerides, glucose and insulin
  • Conditioning exercise energy expenditure.
Description of Actual Data Sample:
  • Initial N: 895 men
  • Attrition (final N): 895 
  • Age: Ranged from 51.7 to 53.4 years
  • Ethnicity: Not given; implied Finnish.

Other Relevant Demographics

Cardiovascular disease (P=0.062)

  • Normoglycaemic: 33.8%
  • IFG: 44.6%
  • DM: 44.1%.

Current smokers

  • Normoglycaemic: 32.6%
  • IFG: 26.8%
  • DM: 29.4%.

Alcohol consumption (grams per week)

  • Normoglycaemic: 32 (7, 96)
  • IFG: 26 (5, 92)
  • DM: 43 (3, 157).

Blood measure medication (P=0.003)

  • Normoglycaemic: 18.9%
  • IFG: 26.8%
  • DM: 38.2%.

Serum total cholesterol (mmol per L; P=0.03)

  • Normoglycaemic: 5.77±1.00
  • IFG: 5.55±0.88
  • DM: 5.73±1.04.

Serum triglycerides (mmol per L; P<0.001)

  • Normoglycaemic: 1.17 (0.84, 1.68)
  • IFG: 1.35 (1.05, 1.97)
  • DM: 1.65 (1.00, 2.26).


BMI (P<0.001)

  • Normoglycaemic: 26.4±3.2kg/m2
  • IFG: 28.2±2.8kg/m2
  • DM: 29.1±4.2kg/m2.

Waist-to-hip ratio (P<0.001)

  • Normoglycaemic: 0.93±0.06
  • IFG: 0.97±0.05
  • DM: 0.96±0.05.


Eastern Finland.

Summary of Results:

 Key Findings

  • 805 men remained normoglycemic; 56 developed IFG and 34 developed DM
  • Men with IFG at the four-year follow-up and especially men who developed DM during follow-up differed already at baseline from the normoglycemic men, with respect to characteristics and conditions associated with insulin resistance
  • Serum esterified and non-esterified SAFA proportions were higher and PUFA proportions lower in men developing DM or IFG. Fat composition of the diet, as recorded with four-day dietary records, was quite similar among the groups.
  • Men with non-esterified linoleate proportions (as shown in Figure 1a of the article) in the upper third were less than half as likely to develop DM or IFG as men in the lower third after adjustment for age only. This remained after adjustment for other confounding factors.
  • Esterified linoleate in the upper third was associated with about half the risk for development of DM or IFG after adjustment for age only, although the association was somewhat attenuated and no longer significant after multivariate adjustment (as shown in Table Two of the article)
  • In covariate analyses, adjusting only for age and baseline glucose levels, higher proportions of fasting non-esterified linoleate and a higher non-esterified linoleate-to-palmitate ratio (upper third 0.33mmol per L vs. lower third 0.49mmol per L, P=0.001 for the trend across tertiles) were associated with smaller increases in fasting glucose levels. The association remained for both after multivariate adjustment.
  • Higher proportions of fasting non-esterified linoleate and a higher non-esterified linoleate-to-palmitate ratio were clearly associated with a more favorable change in fasting insulin levels after adjusting for age and baseline insulin levels. This remained after multivariate adjustment.
  • Higher proportions of esterified linoleate, linolenate and total PUFA as well as higher linoleate-to-palmitate and PUFA-to-SAFA ratios were associated with more favorable changes in insulin during follow-up. Palmitate and total SAFA predicted less favorable changes.
  • In logistic regression analyses with DM or IFG as the dependent variable, linoleate seemed somewhat more protective in the lower BMI category (OR upper vs lower third, 0.31 for BMI under 27kg/m2; OR upper vs. lower third, 0.65 for BMI of at least 27kg/m2, but the BMI-linoleate interaction term was not significant P=0.089). 

Other Findings

  • Dietary composition as assess with the four-day dietary record was not associated with development of DM or IFG
  • Esterified fatty acid proportions did not predict changes in glucose levels during follow-up (as shown in Table Three of the article).
Author Conclusion:

Limitations as cited by the authors:

  • Analysis of serum fatty acid composition reflects the relative proportions of dietary SAFAs and PUFAs, but does not allow interpretation of absolute or total fat consumption
  • SAFAs are in part metabolized into MUFAs, therefore no inferences can be made about dietary monounsaturated fat intake from serum fatty acid composition, at least in populations with a high intake of saturated fat.

High serum linoleate proportions decreased the risk of developing IFG or DM in middle-aged men over a four-year follow-up, possibly mediated in part by insulin resistance.

These findings support recommendations to substitute vegetable fat for animal and dairy fat in the prevention of disturbances of glucose and lipid metabolism.

Funding Source:
Government: Academy of Finland; Ministry of Education of Finland; NIH
Reviewer Comments:

Authors noted that insulin measurements at baseline and four-year follow-up were measured with different kits using different reagents. As a consequence, the four-year insulin concentration was about 15% lower on average than the baseline concentration.

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) N/A
  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) N/A
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? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  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? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  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) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? Yes
  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? Yes
  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%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  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? N/A
  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? No
  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? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  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? N/A
  6.6. Were extra or unplanned treatments described? N/A
  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? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? N/A
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