DF: Cardiovascular Disease (2008)


McKeown NC, Meigs JB, Liu S, et al. Carbohydrate nutrition, insulin resistance, and the prevalance of the metabolic syndrome in the Framingham offspring cohort, Diabetes Care. 2004; 27: 538-546.

PubMed ID: 14747241
Study Design:
Cross-sectional study
D - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To examine the relationship between carbohydrate-related dietary factors, insulin resistance and the prevalence of the metabolic syndrome in the Framingham Offspring Cohort.

Inclusion Criteria:
  • Participants in the fifth examination cycle (1991 to 1995) of the Framingham Offspring Study
  • Completed a Food Frequency Questionnaire (FFQ) and a standardized medical history.
Exclusion Criteria:
  • Extremes in energy intakes:
    • Below 600kcal 
    • Greater than 4,000kcal per day for women
    • Greater than 4,200kcal per day for men
    • More than 13 food items were left blank.
  • On a cholesterol-lowering medication
  • Previously diagnosed with diabetes, based on use of insulin or hypoglycemic medication
  • Missing covariate information
  • Missing values for fasting plasma glucose or insulin concentrations.
Description of Study Protocol:


  • Recruitment to Framingham Offspring Study described previously
  • 3,799 participants in the fifth examination cycle (1991 to 1995) of the Framingham Offspring Study were reviewed for inclusion based on the above criteria
  • After exclusion, 2,834 (1,290 men and 1,544 women) were participants. 


Data collected as part of a semi-quantitative 126-item FFQ, a standardized medical history, fasting glucose and insulin levels and anthropometric measurements (height, weight, waist-to-hip ratio) were examined for associations. Metabolic syndrome was defined as recommended by the National Cholesterol Education Program Adult Treatment Panel. Homeostatis model assessment of insulin resistance (HOMA-IR) was calculated as follows: Fasting plasma insulin x plasma glucose / 22.5. 

Nutrient intake was calculated by multiplying frequency of consumption of each unit of food from the FFQ by nutrient content of specific portions. Dietary exposures included intakes of total carbohydrates, dietary fiber, whole- and refined-grain foods, glycemic index (calculated based on white bread standard) and glycemic load (calculated by multiplying the carbohydrate content of each food by its glycemic index; this value then multiplied by frequency of consumption and summed for all food items). In addition, total dietary fiber was calculated for the food categories: Cereals, fruits, vegetables and legumes.

Statistical Analysis       

  • Natural logarithmic transformations (due to positively skewed data)
  • Inverse transformations (geometric mean HOMA-IR)
  • Linear regression (continuous variable)
  • Mantel-Haenszel x 2 test (categorical variable)
  • Multiple-logistic regression (odds ratio)
  • Significance: P≤0.05.
Data Collection Summary:

Timing of Measurements

Usual dietray intake for the previous year was assessed from the semi-quantitive FFQ that participants brought to the physical examination and standardized medical history. Blood samples were obtained from participants that had fasted at least 10 hours. Data was collected at one visit or timepoint.

Dependent Variables

Metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel.

Independent Variables

  • Energy-adjusted dietary carbohydrate intake
  • Dietary fiber intake
  • Glycemic index
  • Glycemic load.

Control Variables

  • Sex
  • Age
  • Cigarette dose
  • Total energy intake
  • Alcohol intake
  • Percentage saturated and polysaturated fat
  • Multivitamin use
  • Physical activity.
Description of Actual Data Sample:
  • Initial N: 2,834 (1,290 male; 1,544 female)
  • Attrition (final N): Not applicable
  • Age: 54±9.8 years (range, 26 to 82 years)
  • Ethnicity: Not described.

Other Relevant Demographics

Higher quintile HOMA-IR included:

  • More men
  • Older participants
  • Hypertensive individuals
  • Undiagnosed diabetics.


Higher HOMA-IR associated with:

  • Higher BMI
  • Higher waist-to-hip ratio
  • Higher concentration of fasting insulin.


National data collected as part of the Framingham Offspring Cohort.

Summary of Results:

 Insulin Resistance

  • Intakes of total dietary fiber (P<0.001), cereal fiber (P=0.02), fruit fiber (P<0.001) and whole grains (P=0.05) associated with improved IR after adjustment for confounding variables 
    • Association between fruit and cereal fiber and IR remained after adjustment for each other
    • Association between whole grain intake and IR was attenuated after adjustment for cereal and fruit fiber
    • Association between cereal fiber and IR remained after adjustment for whole grains (P=0.003).
  • When modeling included BMI, inverse relationships were observed as dietary fiber, cereal fiber and whole grain increased with increased BMI
  • Total carbohydrate, refined grains and fiber from vegetables and legumes not associated with improved IR
  • Glycemic index (P<0.001) and load (P=0.03) were positively associated with IR.

Metabolic Syndrome

  • Prevalence of metabolic syndrome was significantly lower with high intake of cereal fiber (OR, 0.62; 95% CI, 0.45 to 0.86) and whole grain (OR, 0.67; 95% CI, 0.48 to 0.91) after adjustment for confounding lifestyle and dietary factors
    • Association with whole grains disappeared with adjustment for cereal fibers.
  • Prevalence of metabolic syndrome was significantly higher among individuals in the highest percentiles of glycemic index (OR, 1.41; 95% CI,1.04 to 1.91; P=0.04)
  • Total carbohydrate, dietary fiber, fruit fiber, vegetable fiber, legunme fiber, glycemic load and refined grain intakes not associated with prevalence of metabolic syndrome.
Author Conclusion:
  • A diet containing foods high in dietary fiber, whole grains, cereal and fruit fiber and those with a low glycemic index and glycemic load are associated with significantly less insulin resistance
  • However, only whole grain and cereal fiber intake and glycemic index are associated with decreased incidence of metabolic syndrome.
Funding Source:
Government: USDA, NHLBI
Reviewer Comments:

Cross-sectional analysis of FFQ data.

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? 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? Yes
  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? Yes
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? 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%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  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? No
  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.) No
  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? No
  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? Yes
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)? Yes
  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? 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