Risk of Developing Metabolic Syndrome

Citation:

Lakka TA, Laaksonen DE, et al.  Sedentary Lifestyle, Poor Cardiorespiratory Fitness, and the Metabolic Syndrome.  Med. Sce. Sports Exerc., Vol. 35, No. 8, pp. 1279-1286, 2003.

 
Study Design:
Prospective Cohort Study
Class:
B - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To investigate the cross-sectional associations of leisure-time physical activity and cardiorespiratory fitness with the metabolic syndrome as defined by the WHO in a population-based sample of middle-aged men without diabetes, CV disease, or cancer.
Inclusion Criteria:

Not explicitly stated, but you can assume:

1)  Participant of the KIHD study

2)  Male

3)  Middle-aged

4)  Absence of DM, CV disease, and cancer

5)  Had completed data on physical activity, VO2 max, and the main characteristics of the metabolic snydrome at baseline

6)  Lives in Eastern Finland

7)  Aged 42, 48, 54, or 60 at baseline examinations in 1984-1989

 

Exclusion Criteria:

Never stated in the article, but this can be assumed:

1)  Woman

2)  Non middle-aged

3)  Presence of DM, CV disease, or cancer

4)  Incomplete data on physical activity, VO2 max, and the main characteristics of the metabolic syndrome at baseline

5)  Lived outside of Eastern Finland

Description of Study Protocol:

Recruitment:  Described previously in another article (Salonen, JT.  Is there a continuing need for longitudinal epidemiolobic research?  The Kuopio Ischaemic Heart Disease Risk Factro Study.  Ann. Clin. Res. 20:46-50, 1988.) 

 

Design: 

Subjects completed a validated KIHD 12-month Leisure-Time Physical Activity Questionnaire (Lakka, TA and Salonen JT.  Intra-person variability of various physical activity assessments in the Kuopio Ischaemic Heart Disease Risk Factor Study.  Int. J. Epidemiol. 21:467-472, 1992.  Lakka TA, Venalainen JM, Rauramaa R, et al.  Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction.  N. Engl. J. Med. 330:1549-1554, 1994).  It is a detailed quantitative questionnaire of teh most common conditioning and lifestyle leisure-time physical activities of middle-aged Finnish men.  It enables the assessment of the duration, frequency, adn mean intensity of leisure-time physical activity as recalled over the previous 12 months (low intensity defined as <4.5 METs and moderate-intensity defined as >4.5 METs).   

A graded sumptom-limited maximal exercise test was carried out on an electrically braked cycle ergometer.  Workload was increased linearly.  VO2 max was measured directly with breath-by-breath respiratory gas exchange analysis.

BMI, waist circumference, waist-hip ratio, blood pressure, blood glc, LDL, HDL, TG, apo B, and fibrinogen was measured on each subject.  Assessments of medical history, meds, smoking, alcohol consumption, and adult socioeconomic status were taken.

 

Blinding used (if applicable):  N/A

 

Intervention (if applicable):  N/A

 

Statistical Analysis:   

Performed with SPSS 10.0 for Windows.  Statistical sig was considered to be P<0.05.

1)  Student's t-test and where indicated, the chi-squared test for differences in clinical and biochemical characteristics b/w men who had the metabolic syndrome and those who did not

2)  Partial correlation analysis for cross-sectional associations of leisure-time physical activity and VO2 max with components of or variables related to  the metabolic syndrome

3)  Logistic regression models adjusting first for age, and second for age, smoking, alcohol consumption, and adulthood socioeconomic status for the associations ofleisure-time physical activity and VO2 max with the risk of having the metabolic syndrome.  Ninety-five percent confidence intervals ere estimated based on the assumption of normality.

4)  Factor analysis was carried out using core components of or variables related to the metabolic syndrome, VO2 max, and leisure-time physical activity as a complementary approach for assessing the associations of leisure-time physical activity and cardiorespiratory fitness with the metabolic syndrome (potential confounding factors were also included)

5)  Principal component analysis was used for the extraction of the initial factors.  Only factors with eigenvalues >1.0 were retained in the analysis.  The initial factors were then subjected to promax rotation to generate correlated factors.  The factors were then interpreted as such but also subjected to a secon-order factor analysis with a varimax rotation to assess possible underlying pathophysiological relationships.  Variables with loadings > 0.40 were considered heavily loaded on the factor and variables having a correlation coefficient of 0.30-0.39 to be moderatley loaded.

6)  The durations of leisure-time physical activity are presented as medians; other data are presented as means and standard deviations or simple percentages

7)  Serum TG and insulin and the durations of leisure-time physical activity were corrected for skewing using log transformation but are presented using untransformed values. 

Data Collection Summary:

Timing of Measurements: 

Baseline data on physical activity, VO2 max, and the main characteristics of the metabolic syndrome.

The braked cycled ergometer exercise test was carried out b/w 8 and 10 am.

Subjects were asked to fast for 12 h before blood sampling.  They were also asked to refrain from smoking for 12 h and from consuming alcohol for 3 d before blood draws.

 

Dependent Variables

  • Metabolic syndrome (presence of hyperinsulinemia, impaired fasting glc, or DM & the presence of at least two of the following:  obesity, dyslipidemia, or HTN)

Independent Variables

Age                            Alcohol intake            Waist-hip ratio            TG

BMI                            BP                               LDL                             Apo B

Smoking habits          Waist Girth                  HDL                            Fasting BG/serum insulin

Blood leukocyte count                                   Serun uric acid           Physical activity

Plasma fibrinogen                                          Max O2 uptake          Socioeconomic status

Medications

Control Variables:  N/A

 

Description of Actual Data Sample:

Initial N: unknown

Attrition (final N):  1069 men

Age:  42, 48, 54, or 60 years of age at baseline examinations in 1984-1989

Ethnicity:  unknown 

Other relevant demographics:  absence of CV disease, DM, or cancer 

Anthropometrics: 

                                    Metabolic Syndrome -              Metabolic Syndrome +        P

BMI (kg/m2)                26.1+2.9                                          29.8+3.5                   <0.001

Waist Girth (cm)           88.9+8.5                                         98.8+9.2                    <0.001

Waist-hip ratio              0.94+0.06                                        0.98+0.04                  <0.001

Location:  Eastern Finland 

 

Summary of Results:

Men who engaged in <3.6 hrs/wk of any leisure time physical activity were 64% more likely to have the metabolic syndrome than those participating in > 6.8 hrs/wk after adjusment for age (66% (OR 1.66, 1.09-2.53) after adjustments for age, smoking, alcohol consumption, and SES, P for linear trend 0.026).

Men with <1 hr/wk of at least moderate-intensity activity were 63% more likely ot have the metabolic syndrome than those with >3 hrs/wk of such activity (60% (OR 1.6, 1.04-2.47) after all adjustments, P for trend 0.079).

VO2 max had a strong inverse, and graded assoc w/ the risk of having the metabolic syndrome.  Men w/ the VO2 max <29.1 mL/kg/min had a 6.4-fold and men with the VO2 max 29.1-35.4 mL/kg/min had a 2.8-fold greater likelihood of having the metabolic syndrome than men w/ a VO2 max >35.5 mL/kg/min after adjustment for age.  After further adjustment for other confounders, the least fit men were almost 7 times more likely to have the metabolic syndrome.  Adjustment for BMI weakened the assoc, but men with the VO2 max <29.1 mL/Kg/min and 29.1-35.4 mL/kg/min still had a 3.6-fold (95%CI, P=0.001) and a 1.9-fold (95% CI, P=0.03) increased likelihood of having the metabolic syndrome, respectively.

In the first-order factor analysis, both VO2 max and at least moderate-intensity leisure-time physical activity loaded heavily on the principle factor explaining 20% of the total variance that most strongly characterized the metabolic syndrome.  VO2 max also loaded onto the dyslipidemia factor and the BP factor.  In the second-order factor analysis, VO2 max loaded onto the metabolic syndrome factor.

Age adjusted correlations of total, low-intensity, and at least moderate-intensity leisure-time physical activity and maximal oxygen uptake with core or related features of teh metabolic syndrome in 1069 men without DM, CV dz, or cancer.                                                            

                                                        Leisure Time Physical Activity

                                            Total                Low-intensity       >Moderate intensity        VO2 Max

BMI                                        -0.16                -0.12                             -0.13                       -0.38

Waist girth                            -0.19                -0.13                              -0.17                        -0.46

Waist-hip ratio                       -0.16                -0.11                              -0.16                        -0.34

Fasting BG                                                                                                                             -0.18

Fasting serum insulin              -0.17                -0.12                              -0.17                        -0.32

Serum HDL                                                                                                                              0.24

Serum TG                                                                                                                                -0.28

Serum Apo B                                                                                                                           -0.19

Systolic BP                                                                                                                              -0.15

Diastolic BP                                                                                                                             -0.18

Blood Leukocytes                                                                                                                   -0.17

Plasma fibrinogen                                                                                                                   -0.23

Serum uric acid                    -0.11                  -0.10                                                                -0.20

*All above numbers are P<0.001

Total, at least moderate-intensity, and low-intensity leisure-time physical activity were inversely associated with BMI, waist girth, WHR, and fasting serum insulin.

Total physical activity was negatively correlated with fasting blood glc, serum uric, blood leukocyte count, and diastolic blood pressure, and positively correlated with serum HDL, and HDL2 cholesterol.

At least moderate intensity physical activity showed somewhat stronger inverse associations with measures of abdominal obesity, fasting serum insulin, serum lipds, and blood leukocytes than low-intensity physical activity. 

VO2 max was inversely associated with BMI, waist girth, WHR, fasting BG and serum insulin, TG and apo B, BP, blood leukocytes, plasma fibrinogen, and serum uric acid and directly assoc w/ HDL and HDL2.

VO2 max was also correlated with total leisure-time physical activity (r=0.20, P<0.001) and at least moderate-intensity physical activity (r=0.25, P<0.001).

Author Conclusion:

The findings suggest that a sedentary lifestyle and even more so poor cardiorespiratory fitness could be considered features of the metabolic syndrome.  These data may partly explain our previous observations that low levels of leisure-time physical activity and cardiorespiratory fitness are assoc w/ increased risk for Type 2 DM, CHD, and cardiovascular and overall mortality, as well as accelerated progression of carotid atherosclerosis.  Measurement of VO2 max in sedentary men w/ risk factors may provide an efficient means for targeting individuals who would benefit from interventions to prevent the metabolic syndrome and its consequences.

Overall, the factor analyses suggest that the metabolic syndrome has variable manifestations but that there is nonetheless and underlying pathophysiological commonality.  Using perhaps a biologicaly more relevant approach, strongly predicts CV mortality and incident DM.

Funding Source:
Government: Ministry of Education of Finland
University/Hospital: Academy of Finland, University of Kuopio
Not-for-profit
0
Foundation associated with industry:
Reviewer Comments:

They indicated study concerns (inherent imprecision of physical activity questionnaires, cardiorespiratory fitness has a genetic component).

They stated strengths of the study (VO2 max measured directly using a respiratory gas exchange analysis).

Inclusion and exclusion never explicitly stated.

This study cannot be generalized to women or other ethnicities since they were only males from Finland.

It was random age stratified.

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? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? 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
  2.1. 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? 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
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
  3. Were study groups comparable? 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) N/A
  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? 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.) 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
  3.4. 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
  3.5. 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? Yes
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? 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
  4.4. 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
  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.) 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.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  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? N/A
  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? 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? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments 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
  6.7. 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? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? Yes
  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)? N/A
  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
  8.5. 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? N/A
  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. 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? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
  10. Is bias due to study's funding or sponsorship unlikely? N/A
10. Is bias due to study's funding or sponsorship unlikely? N/A
  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? Yes
  10.2. Was the study free from apparent conflict of interest? Yes