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PDM: Prediabetes (2013)

Citation:

Corpeleijn E, Feskens EJ, Jansen EH, Mensink M, Saris WH, de Bruin TW, Blaak EE. Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: The SLIM study. Diabetologia. 2006; 49 (10): 2,392-2,401.

PubMed ID: 16896932
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate whether intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes.

Inclusion Criteria:
  • Subjects were screened for IGT with a standard OGTT with a capillary sampling 
  • Those with IGT were screened a second time by OGTT and then were included in the study if the mean two-hour glucose concentration was between 7.8 and 12.5mmol/l. 
Exclusion Criteria:

Individuals were excluded if they were:

  • Previously diagnosed diabetes other than gestational diabetes
  • Used medication known to interfere with glucose metabolism
  • Participated in vigorous exercise or an intensive weight loss program in the year prior to participation
  • Any chronic disease that makes participation in a lifestyle program impossible or has an improbable five-year survival.
Description of Study Protocol:

Recruitment

  •  Subjects were recruited from a large existing cohort of the general population
  •  Through advertisements in the local newspaper.

Design

Randomized controlled trial. Subjects were randomized into an intervention or control group with stratification for sex and two-hour glucose value.

Blinding used

Implied with laboratory measurements

Intervention

Lifestyle intervention program consisted of :

  • Dietary recommendations based on the Dutch guidelines including 55% CHO, saturated fat below 10% and cholesterol intake <33mg/MJ
  • Dietitian provided dietary advice on an individual basis after consideration of an individual three-day weighed food record
  • The first visit took place four to six weeks after randomization and a visit was scheduled every three months thereafter
  • Subjects were encouraged to increase their physical activity to at least 30 minutes of moderate physical activity a day for at least five days a week
  • Advice was given on how to increase physical activity and well-defined goals were set which included both aerobic and resistance training
  • Exercise sessions were supervised by trainers and subjects had free access to training sessions of which they were advised to participate in at least one hour per week
  • Once every year the subjects in the control group received oral and written information about the benefits of a healthy diet, weight loss and increased physical activity
  • Control group received no individual advice or programs.

Statistical Analysis

  • Correlations were tested using Pearson's correlation coefficient (r), two-tailed 
  • ANOVA for repeated measures was used to test differences between groups and changes over time
  • Regression analysis was preformed to identify the contribution of changes in life style and fatty acid profile to changes in insulin resistance (HOMA-IR)
  • 95% CI (P<0.05), means±SEM
  • SPSS 10.0 (SPSS, Chicago, IL).
Data Collection Summary:

Timing of Measurements

Baseline and at one year post-intervention.

Dependent Variables

  • Glucose tolerance monitored with standard OGTT
  • Maximal aerobic capacity measured through incremental exhaustive exercise test
  • Body weight, height, skinfold thicknesses, waist circumference
  • Blood samples analyzed for the serum fatty acid profile of cholesteryl esters, plasma glucose, plasma insulin. 

Independent Variables

  • Lifestyle program including diet and exercise
  • Control group.

Control Variables

 

Description of Actual Data Sample:
  • Initial N: Initial N=147
    • N=131 who completed the study at one year
    • Complete data sets at one year for general and metabolic characteristics and serum fatty acid profile of cholesteryl esters were collected on 97 men and women
      • Intervention group: n=47
        • (including n=29 men; n=18 women)
      • Control group: n=50
        • (including n=30 men; n=20 women)
  • Attrition (final N): 
    • A total of n=50 subjects from the original 147 subjects were excluded from the one year data analysis because of incomplete data sets
      • Intervention group: n=27
      • Control group: n=23
  • Age:
    • Intervention: 56.0±0.9 years
    • Control: 58.5±1.0 years
  • Ethnicity: Not mentioned
  • Other relevant demographics:
  • Anthropometrics: No significant differences between the groups were mentioned, it is unclear if differences were statistically analyzed for significance.
  • Location: The Netherlands.

 

Summary of Results:

The lifestyle program was effective in reducing the intake of total and saturated fat, increasing physical activity, reducing obesity and improving insulin sensitivity and glucose tolerance.

After one year of lifestyle intervention:

  • Body weight and BMI decreased
  • VO2 was increased
  • Improvements in two-hour glucose, fasting insulin and HOMA-IR were observed.
  Intervention Group Baseline Intervention Group 1 Year Statistical Significance of Group Difference
(Group x Time)

Body weight (kg)

BMI (kg/m2)

88.2±1.9

29.7±0.5

85.4±1.8

28.8±0.5

P<0.01

P=0.01

Two-hour glucose (mmol/l)

Fasting insulin (mU/l)

HOMA-IR*

VO2max

 

9.0±0.3

17.9±1.2

5.00±0.04

40.9±1.0

 

8.1±0.3

15.5±1.1

4.22±0.35

43.3±1.1

 

P<0.01

P=0.04

P=0.04

P=0.03

 

 *HOMA-IR = homeostasis model assessment for insulin resistance 

Other Findings

  • No direct changes were observed in the individual fatty acid fractions after one year
    • Myristic, palmitoleic, y-linolenic acid, and dihomo-ylinolenic acid correlated positively with changes in HOMA-IR
    • Inverse relationship was observed with oleic and arachidonic acid and changes in HOMA-IR.
  1. Pearson correlation coefficients for the relationships between fasting insulin and changes in desaturase
  2. Pearson correlation coefficient for the associations between changes in fasting glucose and changes in desaturase.
Desaturase Fasting  Insulin(1) Fasting Glucose(2)
n-9 r=0.151 (p=0.067) r=0.199 (p=0.045)
n-6 r=0.196 (p=0.016) r=0.287 (p=0.003)
n-5 r=0.243 (p=0.002) r=0.210 (p=0.033)
  • In a regression analysis of the total group, a relevant interaction between fat intake (below or above 35.5%) and change in n-9 desaturase activity was found (P=0.13)
  • In the intervention group, fasting glucose was reduced (6.1±0.1 to 6.0±0.1 mmol/L, P=0.05).
  • There were no significant differences in waist circumference or hemoglobin A1C between groups. Blood pressure, lipid and renal outcomes were not reported.

 

Author Conclusion:
  1. Lifestyle-induced improvements in insulin sensitivity are independently explained by specific changes in the fatty acid profile of serum cholesteryl esters
  2. An increase in insulin sensitivity is associated with an increase in estimated n-5 desaturase activity and a decrease in estimated n-6 and n-9 desaturase activities
  3. Associations between changes in insulin resistance remained significant after adjustments for changes in diet, VO2max, and/or body fat percentage.

 

Funding Source:
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:
  • No description of the population was given (ethnicity, education level, occupation, etc.)
  • Not enough information was provided to determine if the study population and selection was free from bias
  • A total of 50 from the original sample of 147 were lost to attrition or had incomplete records
  • It was unclear if the funding source was not associated with bias.

 

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
  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
  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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? Yes
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.1. 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
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? No
  1.3. Were the target population and setting specified? No
  2. Was the selection of study subjects/patients free from bias? ???
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
  2.1. 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
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  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? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
  3. Were study groups comparable? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) 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? 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? 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
  3.5. 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
  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. Was method of handling withdrawals described? ???
  4.1. Were follow-up methods described and the same for all groups? 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
  4.2. 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? ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? 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
  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. 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
  5.1. 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
  5.2. 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
  5.3. 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
  5.4. 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
  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. 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
  6.1. 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
  6.2. 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
  6.3. 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
  6.4. 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments 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
  6.7. 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
  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. 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
  7.1. 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
  7.2. 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
  7.3. 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
  7.4. 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
  7.5. 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
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? 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. 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
  8.1. 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
  8.2. 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
  8.3. 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)? No
  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)? No
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? 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
  8.6. 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
  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. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
  9.2. Are biases and study limitations identified and discussed? No
  10. Is bias due to study's funding or sponsorship unlikely? ???
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? ???
  10.2. Was the study free from apparent conflict of interest? ???