Endocrine DOI 10.1007/s12020-013-0110-0
META-ANALYSIS
Association between leisure time physical activity and metabolic syndrome: a meta-analysis of prospective cohort studies Dan He • Bo Xi • Jian Xue • Pengcheng Huai Min Zhang • Jun Li
•
Received: 24 August 2013 / Accepted: 30 October 2013 Ó Springer Science+Business Media New York 2013
Abstract A great number of prospective studies have investigated the relationship between leisure time physical activity (LTPA) and metabolic syndrome (MetS) risk. However, the results have been inconsistent. The aim of this study was to clarify the relationship between LTPA and MetS risk. Literature databases were searched including PubMed and Embase up to June 2013. A total of 17 studies, including 64,353 participants and 11,271 incident cases, were included in the meta-analysis. A high level of LTPA was statistically associated with decreased risk of MetS [high vs. low: relative risk (RR) = 0.80, 95 % confidence interval (CI) 0.75–0.85], whereas a moderate level of LTPA was weakly associated with decreased risk of MetS (moderate vs. low: RR = 0.95, 95 % CI 0.91–1.00). Subgroup analyses indicated that the association between a moderate level of LTPA and decreased risk of MetS was only significant in men (moderate vs. low: RR = 0.88, 95 % CI 0.81–0.97) and in studies with more than a 10-year follow-up period (moderate vs. low: RR = 0.90, 95 % CI 0.84–0.97). A high level of LTPA was statistically
Dan He and Bo Xi have contributed equally to this work. D. He B. Xi (&) J. Xue M. Zhang J. Li (&) Department of Maternal and Child Health Care, School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan 250012, People’s Republic of China e-mail: [email protected] J. Li e-mail: [email protected] P. Huai Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, People’s Republic of China
associated with decreased risk of MetS in each subgroup. A higher level of LTPA is associated with a lower risk of MetS. These findings could have public health implications with regard to prevention of MetS through lifestyle interventions. Keywords Metabolic syndrome Leisure time physical activity Prospective study Meta-analysis
Introduction Metabolic syndrome (MetS) is a major public health problem worldwide. MetS is characterized by a clustering of risk factors, including obesity, hypertension, dyslipidemia, hyperglycemia, and hyperinsulinemia [1]. Epidemiological studies have indicated that MetS is associated with increased risk of type 2 diabetes and cardiovascular diseases (CVDs) [2]. Thus, prevention of the MetS is a key public health target. Genetic factors [3], inflammatory factors [4], adipokines [5], dietary patterns, and lifestyle factors [6] are thought to contribute to the pathogenesis of MetS. Previous reviews have commented on the association between leisure time physical activity (LTPA) and risk of MetS [7–9]. However, the evidence was mainly based on findings from crosssectional studies which limited causality inference. Recently, a great number of prospective studies have investigated the relationship between LTPA and MetS risk [10–23]. However, the findings have been inconsistent and no meta-analysis of prospective studies on this topic has been published. The aim of this study was therefore to clarify the relationship between LTPA and MetS risk by combining all related published prospective studies.
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Materials and methods Literature and search strategy Literature databases were searched including PubMed and Embase. The search strategy to identify all possible studies involved the use of the following key words: (physical activity OR PA OR exercise) and (MetS OR MetS 9 OR syndrome 9 OR cardiometabolic risk factor OR insulin resistance syndrome) and (cohort OR prospective OR longitudinal OR follow-up). The reference lists of retrieved articles were hand searched. The literature search was limited to the English language. The literature search was updated on June 20, 2013. Inclusion criteria and data extraction The studies included in the meta-analysis met all the following inclusion criteria: (1) evaluated the association between LTPA and MetS; (2) used prospective design; and (3) provided covariates’ adjusted relative risk (RR) with 95 % confidence interval (CI). The following information was extracted from each study: (1) name of the first author; Fig. 1 Flow chart of metaanalysis for exclusion/inclusion of individual articles (or studies)
(2) year of publication; (3) origin of country; (4) number of incident MetS cases and total population; (5) sex ratio and age of the study population; (6) duration of follow-up; (7) MetS criteria; (8) measurement of LTPA; (9) definition of low, moderate, and high levels of LTPA; and (10) covariates used in adjustment. The two authors independently assessed the articles for compliance with the inclusion/ exclusion criteria and resolved disagreements through discussion. Statistical analysis In this meta-analysis, LTPA was categorized to three levels: low, moderate, and high. The association of LTPA with MetS was estimated by calculating pooled OR and 95 % CI. The significance of pooled OR was determined by Z test (p \ 0.05 was considered statistically significant). A Q test was performed to examine the between-study heterogeneity. A random (DerSimonian–Laird method [24]) or fixed (Mantel–Haenszel method [25]) effects model was used to calculate pooled OR in the presence (p B 0.10) or absence (p [ 0.10) of heterogeneity, respectively. Subgroup analyses were conducted based on
Articles identified through database search (n=1449) Articles excluded: · Obvious irrelevance after titles and abstracts evaluated (n=1401) Articles screened (n =48) Articles excluded: · MS not an outcome (n=8) · PA not an exposure (n=6) · Cross-sectional or case-control design (n=12) · Reviews (n=2) Full-text of the articles accessed for eligibility (n =20 ) Articles excluded: · No RR with 95%CI (n=3) · Total population less than 500 (n=1) · Occupational physical activity (n=2) 14 articles included in the meta-analysis with a total of 17 cohorts*
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*Note: three articles (Wilsgaard et al., 2007;Yang, et al., 2008; Silveira et al., 2010) contained a total of 6 cohorts
28
13.8
USA
UK
Norway
Norway
Carnethon et al. [11]
Wannamethee et al. [12]
Holme et al. [13]
Wilsgaard and Jacobsen [14] (men)
20
13.6
4
Finland
Laaksonen et al. [10]
Followup year
Country
Study
1,169
1,597
790
575
107
No. of MetS cases
Age: 20–61 years
All were men
Total: 8,536
Age: 40–49 years
All were men
Total: 6,410
Age: 60–79 years
All were men
Total: 3,051
Age: 18–30 years
Women: 2,323
Men: 1,869
Total: 4,192
Age: 42–60 years
All were men
Total: 612
Population (sex ratio, age)
NCEP ATPIII
Based on the intensity of LTPA by questionnaire
Based on the intensity, duration, and frequency of LTPA by questionnaire
NCEP ATPIII
Based on the average duration and intensity of LTPA by questionnaire
NCEP ATPIII
Based on the frequency and intensity of LTPA by questionnaire
Based on the duration, frequency, and intensity of LTPA by questionnaire
WHO
NCEP ATPIII
Measurement of LTPA
Definition for MetS
Table 1 Characteristics of prospective studies included in the meta-analysis
High: C7.5 METs
Moderate: 4.5–7.5 METs
Low: \4.5 metabolic equivalents (METs)
High: hard training or competition sports regularly several times a week
Moderate: walking, bicycling, or other forms of physical activity including walking or bicycling to and from the place of work and a Sunday walk totaling at least four hours a week; or exercise, sports, heavy gardening, and similar activities totaling at least 4 h a week
Low: usually reading, watching television, or other sedentary occupations at leisure
Moderate: PA score ranging from 6 to 12 High: PA score more than 13
Low: PA score \5
High: PA score above the median at all four examinations
Moderate: PA score fluctuated around the median at all four examinations
Low: PA score below the median at all four examinations (In 1985, 1992, 1995, 2000)
High: C487 min/week
Alcohol intake, coffee consumption, number of cigarettes smoked, year of education
Age, years of education, glucose, triglycerides, body mass index, treated, hypertension and systolic blood pressure at baseline
Age, social class, smoking, alcohol intake, body mass index, dietary fat, and carbohydrate intake
Age category, BMI, waist-to-hip ratio, use of antihypertensive medications, systolic and diastolic blood pressure, and concentrations of HDL, triglycerides insulin, glucose levels, and family history of diabetes Age, race, sex, weight gain, and physical activity over time, education, baseline BMI, baseline physical activity, smoking status, drinking status, crude fiber, total dietary fat intake, and carbohydrate intake
Low: \270 min/week Moderate: 270–486 min/week
Adjustments
Definition of low, moderate and high levels of LTPA
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Country
Norway
Finland
Finland
USA
Japan
USA
Study
Wilsgaard and Jacobsen [14] (women)
Yang et al. [15] (men)
Yang, et al. [15] (women)
Cheriyath et al. [16]
Li et al. [17]
Peterson et al. [18]
Table 1 continued
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5
3
6
9
9
13.8
Followup year
299
285
1,970
95
146
965
No. of MetS cases
Age: 70–79 years
Women: 718
Men: 778
Total: 1,496
Age: 35–60 years
Total: 1,897 All were men
Age: 45–64 years
Men: 3,456 Women: 4,398
Total: 7,854
Age: 24–39 years
All were women
Total: 1,099
Age: 24–39 years
All were men
Total: 961
Age: 20–61 years
Total: 8,463 All were women
Population (sex ratio, age)
Based on the intensity, frequency, and duration of LTPA by questionnaire Based on the intensity, frequency, and duration of LTPA by questionnaire Based on the duration and intensity of LTPA by questionnaire
NCEP ATPIII
NCEP ATPIII
NCEP ATPIII
NCEP ATPIII
Based on the duration and frequency of LTPA by questionnaire
Based on the duration, frequency, and intensity of LTPA by questionnaire
Based on the intensity of LTPA by questionnaire
NCEP ATPIII
AHA/ NHLBI
Measurement of LTPA
Definition for MetS
High: walking a minimum of 150 min/week at both year 1 and year 6
Moderate: walking a minimum of 150 min/week at year 1 and \150 min/week at year 6, or walking \150 min/week at year 1 and equal to or[150 min/week at year 6.
Low: walking \150 min/week at year 1 and at year 6
PA 3 days or more and 90 min or more in total per week
Low: not regularly Moderate: moderate or vigorous
High: PA score at the highest tertile (C2.75)
Moderate: PA score at the middle tertile (2.25–2.50)
Low: PA score at the lowest tertile (1.00–2.00)
High: PA index at the highest tertile
Moderate: PA index at the middle tertile
Low: PA index at the lowest tertile
High: PA index at the highest tertile
Moderate: PA index at the middle tertile
Low: PA index at the lowest tertile
High: C7.5 METs
Year 1 body weight, race, education, number of diagnoses, heart disease, and year 1 min/week in highintensity exercise
Age, BMI, Number of healthy eating behaviors, smoking status, weight change since one’s mid-twenties
Baseline age, race, sex, education, smoking, prevalent CHD, total cholesterol, sampling weight, and BMI
Age, smoking, and education
Age, smoking, and education
Alcohol intake, coffee consumption, number of cigarettes smoked, year of education
Low: \4.5 metabolic equivalents (METs) Moderate: 4.5–7.5 METs
Adjustments
Definition of low, moderate and high levels of LTPA
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Country
Brazil
Brazil
Finland
Denmark
USA
Study
Silveira et al. [19] (men)
Silveira et al. [19] (women)
Ja¨a¨skela¨inen et al. [20]
Laursen et al. [21]
Bradshaw et al. [22]
Table 1 continued
9
10
27
22
22
Followup year
1,840
585
396
81
132
No. of MetS cases
Age: 54 ± 6 years
Women: 5,517
Men: 3,686
Total: 9,203
Age: 21–98 years
Men: 1,579 Women: 2,389
Total: 3,968
Age: 3–18 years
Women: 1,157
Men: 971
Total: 2,128
All were women
Total: 1,761
Total: 1,834 All were men
Population (sex ratio, age)
NCEP ATPIII
AHA/ NHLBI
Harmonized criteria
NCEP ATPIII
NCEP ATPIII
Definition for MetS
Based on the duration and intensity of LTPA by questionnaire
Based on the frequency, duration, and intensity of LTPA by questionnaire
Based on the frequency and intensity of LTPA by questionnaire
Based on the duration and intensity of LTPA by questionnaire
Based on the duration and intensity of LTPA by questionnaire
Measurement of LTPA
High: PA score more than 2.75
Moderate: PA score from 2 to 2.75
Low: PA score \2
High: light PA [4 or 2–4 h/week of more vigorous PA (e.g., brisk walking, fast biking, heavy gardening work, sport that causes perspiration or exhaustion) or more than 4 h/week of moderate PA or regular heavy exercise or competitive sports several times per week
Moderate: light PA 2–4 h/week
Low: sedentary or light PA (e.g., slow walking/biking, light gardening work) \2 h/week
Moderate: Per unit increase for PA score
High: more than 150 min
Moderate: 10–140 min
Low: \10 min
Age, sex, ethnicity, education, smoking, drinking, energy intake
Age, cohabitation, education, alcohol, smoking, income, duration of schooling, jogging, walking speed and volume
Age, sex, triglycerides, insulin, BMI, systolic blood pressure, HDL cholesterol, family history of hypertension, CRP, family history of diabetes, parents’ education, vegetable consumption, fruit consumption, fish consumption, LDL cholesterol, butter use on bread
Alcohol intake, smoking, low fiber, high fat intake
Alcohol intake, smoking, low fiber, high fat intake
Low: \10 min Moderate: 10–140 min High: more than 150 min
Adjustments
Definition of low, moderate and high levels of LTPA
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Age: 16 years
Women: 424
MetS metabolic syndrome, WHO World Health Organization, NCEP ATPIII National Cholesterol Education Program Adult Treatment Panel III, AHA/NHLBI American Heart Association/ National Heart Lung and Blood Institute, and IDF International Diabetes Federation
High: daily
Moderate: several times/week
Sex, socioeconomic disadvantage, family history of diabetes, BMI, intake of sweets/ pastries, alcohol consumption, smoking, and TV viewing/ leisure time physical activity at age 16 years, physical activity at age 43 years Low: less than once a week
Based on the frequency of LTPA by questionnaire IDF Total: 888 Men: 464 239 Sweden Wennberg et al. [23]
27
Country Study
Table 1 continued
Followup year
No. of MetS cases
Population (sex ratio, age)
Definition for MetS
Measurement of LTPA
Definition of low, moderate and high levels of LTPA
Adjustments
Endocrine
sex, duration of follow-up, and definitions of MetS. Sensitivity analysis after excluding one study at a time was performed to assess the stability of the results. Publication bias was assessed by Begg’s test [26] (p \ 0.05 was considered statistically significant). Statistical analysis was conducted using STATA version 11 (StataCorp LP, College Station, TX, USA).
Results Characteristics of the studies A flow chart of meta-analysis for exclusion/inclusion of individual articles (or studies) is presented as Fig. 1. In brief, the literature search identified a total of 1,449 potentially relevant papers. 1,401 papers were excluded after reading the title and abstract because of obvious irrelevance at the first step. Furthermore, 28 articles were excluded because they were reviews, based on cross-sectional or case–control design, did not consider MetS as an outcome, or did not consider LTPA as an exposure. Then, 20 articles met the primary inclusion criteria. However, six articles were further excluded because three articles did not provide RR and 95 % CI, one article included \500 individuals free of MetS at baseline since a study with small sample size usually reports false positive result, and two articles investigated the association between occupational PA and MetS risk. In addition, since the data were provided by sex in each of three papers [14, 15, 19], they were considered as the separate studies in the following data analysis. Therefore, 14 articles with a total of 17 studies (64,353 participants and 11,271 incidence cases) were included in the final meta-analysis [10–23]. Of them, 15 studies used the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria, the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria, or the Harmonized criteria (these three criteria are uniform) to define MetS; one used the World Health Organization (WHO) criteria; and the rest one used the International Diabetes Federation criteria (IDF) criteria. The characteristics of the included prospective studies are presented in Table 1. Meta-analysis results A moderate level of LTPA was weakly associated with decreased risk of MetS (moderate vs. low: RR = 0.95, 95 % CI 0.91–1.00, Fig. 2), with no evidence of betweenstudy heterogeneity (I2 = 18.3 %, p for heterogeneity = 0.239). A high level of LTPA was statistically associated with decreased risk of MetS (high vs. low: RR = 0.80, 95 % CI 0.75–0.85, Fig. 3), with no evidence
Endocrine
Fig. 2 Meta-analysis of the association between moderate level of LTPA and risk of developing MetS
Fig. 3 Meta-analysis of the association between high level of LTPA and risk of developing MetS
of between-study heterogeneity (I2 = 17.1 %, p for heterogeneity = 0.262). Subgroup analyses by sex, duration of follow-up, and diagnostic criteria were performed. The results indicated that a moderate level of LTPA was statistically associated with decreased risk of MetS in men (moderate vs.
low: RR = 0.88, 95 % CI 0.81–0.97, Table 2) and in studies with a duration of follow-up more than 10 years (moderate vs. low: RR = 0.90, 95 % CI 0.84–0.97, Table 2). A high level of LTPA was statistically associated with decreased risk of MetS in each subgroup (Table 2).
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Endocrine Table 2 Subgroup analysis of the association between LTPA and MetS RR (95 % CI)
Statistical model
I2 (%)
pH
17
0.95 (0.91–1.00)
Fixed
18.3
0.239
8
0.88 (0.81–0.97)
Fixed
6.5
0.380
4
0.99 (0.86–1.14)
Fixed
10.8
0.339
No. of studies Moderate versus low All Sex Men Women
Duration of follow-up \10
7
1.00 (0.94–1.07)
Fixed
37.8
0.140
C10
10
0.90 (0.84–0.97)
Fixed
0.0
0.782
0.96 (0.91–1.01)
Fixed
19.2
0.239
0.76 (0.55–1.04)
Fixed
0.0
0.724
15
0.80 (0.75–0.85)
Fixed
17.1
0.262
7
0.71 (0.63–0.80)
Fixed
0.0
0.941
4
0.68 (0.54–0.85)
Fixed
0.0
0.834
Diagnostic criteria NCEP ATPIIIa Others
15 2
High versus low All Sex Men Women
b
Duration of follow-up \10
6
0.85 (0.79–0.91)
Fixed
32.5
0.192
C10
9
0.71 (0.64–0.78)
Fixed
0.0
0.995
13
0.80 (0.76–0.85)
Fixed
16.8
0.274
2
0.54 (0.34–0.88)
Fixed
0.0
0.971
Diagnostic criteria NCEP ATPIIIa Others
pH, p value for between-study heterogeneity a
AHA/NHLBI or Harmonized criteria Two studies by Li et al. [17] and Ja¨a¨skela¨inen et al. [20] did not provide the RR with 95 % CI for high level of LTPA
b
Sensitivity analyses and publication bias After excluding one study at a time, the sensitivity analyses confirmed the statistical association between a high level of LTPA and decreased risk of MetS [RR with 95 % CI ranging from 0.78 (0.73–0.83) to 0.80 (0.76–0.85)] and the weak association between a moderate level of LTPA and decreased risk of MetS [RR with 95 % CI ranging from 0.92 (0.87–0.98) to 0.96 (0.91–1.01)]. No publication bias was detected for both moderate (p = 0.064) and high (p = 0.729) levels of LTPA.
Discussion To our knowledge, this is the first meta-analysis of prospective cohort studies reporting the association between LTPA and development of MetS. The results indicated that high LTPA was significantly associated with decreased risk
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of MetS, whereas moderate LTPA was weakly associated with incident MetS compared to those who were inactive, after adjustment for potential confounding factors. In the stratified subgroups, the association between moderate LTPA and MetS was significant in men and in studies with more than a 10-year follow-up period; high LTPA decreased the risk of MetS regardless of sex, duration of follow-up, and the MetS definitions used. To date, 14 articles including a total of 17 prospective studies have examined the association between LTPA and risk of MetS. However, they have revealed conflicting findings. The discrepancy might be due to differences in sex ratio, duration of follow-up, and diagnosis criteria of MetS for each included study. In 2002, Laaksonen et al. [10] firstly reported that high rather than moderate LTPA had a beneficial effect on the risk of MetS in a 4-year follow-up study of 612 middle-aged men without MetS at baseline. The following studies demonstrated either significant [11, 12, 14, 15, 18, 22] or non-significant [13, 16, 19, 21] association for high LTPA. In this study, the pooled RR combining all published prospective studies confirmed the significant association of high LTPA with risk of MetS. To observe whether sex, duration of follow-up, and definition of MetS influence the association between LTPA and MetS risk, we further performed subgroup analyses based on those three variables. The significant association for moderate LTPA was only found in men and in studies with more than a 10-year follow-up period, suggesting the sex-specific effect on the association, and moderate activity might have an effect, but takes longer to show results. Different definitions for MetS have been proposed, including WHO [27], NCEP ATP III [28], IDF [29], AHA/NHLBI [30], and the updated Harmonized definition [31]. These definitions share several characteristics, but on some features, they are different. Indeed, three definitions including NCEP ATP III, AHA/NHLBI, and the updated Harmonized definition are uniform. Thus, the studies using those three criteria were pooled together in the subgroup analysis. The association between LTPA and MetS risk was not influenced by the different definitions used. Several meta-analyses with prospective studies have investigated the association of LTPA with other chronic diseases, including coronary heart disease [32], stroke [33], type 2 diabetes [34], hypertension [35], various types of cancer [36–38], and mortality [39, 40]. These publications showed an association of LTPA with the diseases and mortality, which was similar to our finding. That is, LTPA is beneficial for prevention and control of many chronic diseases. Public health guidelines for weekly physical activity recommend accumulating a minimum of 150 min/ week of moderate intensity physical activity (such as brisk walking) [41]. Our results highlight the need to target
Endocrine
LTPA, especially high LTPA, to prevent the development of MetS in the general population. Our study has several major strengths. First, all included studies were prospective population based, enabling us to investigate the causal inference between LTPA and MetS. Second, the statistical power of the study was reasonably high since it included more than 10,000 incident cases. Third, we used covariates’ adjusted RRs with 95 % CIs from individual studies to get the pooled estimate, which had ruled out the effect of confounding factors on the association. However, three limitations of the present study should be noted. First, LTPA was self-reported in all the included studies, which may affect its precision as a predictor. Second, the definitions of low, moderate, and high LTPA were different among the included studies. Third, we studied only LTPA, not occupational PA since only two prospective studies have investigated the association between occupational PA and development of MetS [42, 43]. Actually, both studies showed the protective effect of occupational PA with risk of MetS. In conclusion, a higher level of LTPA is associated with a lower risk of MetS. Individuals should be recommended to take part in regular high LTPA to prevent the risk of developing MetS and related type 2 diabetes and CVDs. Acknowledgments This work was supported by the Research Fund for the Doctoral Program of Higher Education of China (20120131120004). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of interest
7.
8.
9.
10.
11.
12.
13.
14.
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None. 17.
References 18. 1. E.A. Gale, The myth of the metabolic syndrome. Diabetologia 48, 1679–1683 (2005) 2. P.W. Wilson, R.B. D’Agostino, H. Parise, L. Sullivan, J.B. Meigs, Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 112, 3066–3072 (2005) 3. J.H. Zhang, N.F. Li, Z.T. Yan, L. de Zhang, H.M. Wang, Y.Y. Guo, Z. Ling, Association of genetic variations of PRDM16 with metabolic syndrome in a general Xinjiang Uygur population. Endocrine 41, 539–541 (2012) 4. T. Yang, C.H. Chu, P.C. Hsieh, C.H. Hsu, Y.C. Chou, S.H. Yang, C.H. Bai, S.L. You, L.C. Hwang, T.C. Chung, C.A. Sun, C-reactive protein concentration as a significant correlate for metabolic syndrome: a Chinese population-based study. Endocrine 43, 351–359 (2013) 5. T. Stefanov, M. Blu¨her, A. Vekova, I. Bonova, S. Tzvetkov, D. Kurktschiev, T. Temelkova-Kurktschiev, Circulating chemerin decreases in response to a combined strength and endurance training. Endocrine (2013). doi:10.1007/s12020-013-0003-2 6. C.H. Tsai, T.C. Li, C.C. Lin, H.S. Tsay, Factor analysis of modifiable cardiovascular risk factors and prevalence of
19.
20.
21.
22.
metabolic syndrome in adult Taiwanese. Endocrine 40, 256–264 (2011) S. Carroll, M. Dudfield, What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. Sports Med. 34, 371–418 (2004) B.C. Guinhouya, H. Samouda, D. Zitouni, C. Vilhelm, H. Hubert, Evidence of the influence of physical activity on the metabolic syndrome and/or on insulin resistance in pediatric populations: a systematic review. Int. J. Pediatr. Obes. 6, 361–388 (2011) J.R. Churilla, R.F. Zoeller, Physical activity: physical activity and the metabolic syndrome: a review of the evidence. AJLM 2, 118–125 (2008) D.E. Laaksonen, H.M. Lakka, J.T. Salonen, L.K. Niskanen, R. Rauramaa, T.A. Lakka, Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25, 1612–1618 (2002) M.R. Carnethon, C.M. Loria, J.O. Hill, S. Sidney, P.J. Savage, K. Liu, Coronary Artery Risk Development in Young Adults study, Risk factors for the metabolic syndrome: the Coronary Artery Risk Development in Young Adults (CARDIA) study, 1985–2001. Diabetes Care 27, 2707–2715 (2004) S.G. Wannamethee, A.G. Shaper, P.H. Whincup, Modifiable lifestyle factors and the metabolic syndrome in older men: effects of lifestyle changes. J. Am. Geriatr. Soc. 54, 1909–1914 (2006) I. Holme, S. Tonstad, A.J. Sogaard, P.G. Larsen, L.L. Haheim, Leisure time physical activity in middle age predicts the metabolic syndrome in old age: results of a 28-year follow-up of men in the Oslo study. BMC Public Health 7, 154 (2007) T. Wilsgaard, B.K. Jacobsen, Lifestyle factors and incident metabolic syndrome. The Tromsø Study 1979-2001. Diabetes Res. Clin. Pract. 78, 217–224 (2007) X. Yang, R. Telama, M. Hirvensalo, N. Mattsson, J.S. Viikari, O.T. Raitakari, The longitudinal effects of physical activity history on metabolic syndrome. Med. Sci. Sports Exerc. 40, 1424–1431 (2008) P. Cheriyath, Y. Duan, Z. Qian, L. Nambiar, D. Liao, Obesity, physical activity and the development of metabolic syndrome: the atherosclerosis risk in communities study. Eur. J. Cardiovasc. Prev. Rehabil. 17, 309–313 (2010) Y. Li, H. Yatsuya, H. Iso, K. Tamakoshi, H. Toyoshima, Incidence of metabolic syndrome according to combinations of lifestyle factors among middle-aged Japanese male workers. Prev. Med. 51, 118–122 (2010) M.J. Peterson, M.C. Morey, C. Giuliani, C.F. Pieper, K.R. Evenson, V. Mercer, M. Visser, J.S. Brach, S.B. Kritchevsky, B.H. Goodpaster, S. Rubin, S. Satterfield, E.M. Simonsick, Health ABC Study, Walking in old age and development of metabolic syndrome: the health, aging, and body composition study. Metab. Syndr. Relat. Disord. 8, 317–322 (2010) V.M. Silveira, B.L. Horta, D.P. Gigante, M.R. Azevedo, Metabolic syndrome in the 1982 Pelotas cohort: effect of contemporary lifestyle and socioeconomic status. Arq. Bras. Endocrinol. Metabol. 54, 390–397 (2010) P. Ja¨a¨skela¨inen, C.G. Magnussen, K. Pahkala, V. Mikkila¨, M. Ka¨ho¨nen, M.A. Sabin, M. Fogelholm, N. Hutri-Ka¨ho¨nen, L. Taittonen, R. Telama, T. Laitinen, E. Jokinen, T. Lehtima¨ki, J.S. Viikari, O.T. Raitakari, M. Juonala, Childhood nutrition in predicting metabolic syndrome in adults: the cardiovascular risk in Young Finns Study. Diabetes Care 35, 1937–1943 (2012) A.H. Laursen, O.P. Kristiansen, J.L. Marott, P. Schnohr, E. Prescott, Intensity versus duration of physical activity: implications for the metabolic syndrome. A prospective cohort study. BMJ Open 2, e001711 (2012) P.T. Bradshaw, K.L. Monda, J. Stevens, Metabolic syndrome in healthy obese, overweight, and normal weight individuals: the
123
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23.
24. 25.
26.
27.
28.
29.
30.
31.
32.
atherosclerosis risk in communities study. Obesity (Silver Spring) 21, 203–209 (2013) P. Wennberg, P.E. Gustafsson, D.W. Dunstan, M. Wennberg, A. Hammarstro¨m, Television viewing and low leisure-time physical activity in adolescence independently predict the metabolic syndrome in mid-adulthood. Diabetes Care 36, 2090–2097 (2013) R. DerSimonian, N. Laird, Meta-analysis in clinical trials. Control Clin. Trials 7, 177–188 (1986) N. Mantel, W. Haenszel, Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl Cancer Inst. 22, 719–748 (1959) C.B. Begg, M. Mazumdar, Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088–1101 (1994) K.G. Alberti, P.Z. Zimmet, Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet. Med. 15, 539–553 (1998) S.M. Grundy, H.B. Brewer, J.I. Cleeman, S.C. Smith, C. Lenfant, American Heart Association; National Heart, Lung, and Blood Institute, Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109, 433–438 (2004) The IDF consensus worldwide definition of the metabolic syndrome. http://www.idf.org/webdata/docs/MetS_def_update2006. pdf.(2006).Accessed 14 Nov 2013 S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J. Gordon, R.M. Krauss, P.J. Savage, S.C. Smith, J.A. Spertus, F. Costa, American Heart Association; National Heart, Lung, and Blood Institute, Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung and Blood Institute scientific statement. Circulation 112, 2735–2752 (2005) K.G. Alberti, R.H. Eckel, S.M. Grundy, P.Z. Zimmet, J.I. Cleeman, K.A. Donato, J.C. Fruchart, W.P. James, C.M. Loria, S.C. Smith, International Diabetes Federation TaskForce on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity, Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009) J. Sattelmair, J. Pertman, E.L. Ding, H.W. Kohl, W. Haskell, I.M. Lee, Dose response between physical activity and risk of
123
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
coronary heart disease: a meta-analysis. Circulation 124, 789–795 (2011) J. Li, J. Siegrist, Physical activity and risk of cardiovascular disease–a meta-analysis of prospective cohort studies. Int. J. Environ. Res. Public Health 9, 391–407 (2012) C.Y. Jeon, R.P. Lokken, F.B. Hu, R.M. van Dam, Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care 30, 744–752 (2007) P. Huai, H. Xun, K.H. Reilly, Y. Wang, W. Ma, B. Xi, Physical activity and risk of hypertension: a meta-analysis of prospective cohort studies. Hypertension (2013). doi:10.1161/HYPERTENSIONAHA. 113.01965 Y. Je, J.Y. Jeon, E.L. Giovannucci, J.A. Meyerhardt, Association between physical activity and mortality in colorectal cancer: a meta-analysis of prospective cohort studies. Int. J. Cancer (2013). doi:10.1002/ijc.28208 Y. Wu, D. Zhang, S. Kang, Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res. Treat. 137, 869–882 (2013) J.Y. Sun, L. Shi, X.D. Gao, S.F. Xu, Physical activity and risk of lung cancer: a meta-analysis of prospective cohort studies. Asian Pac. J. Cancer Prev. 13, 3143–3147 (2012) D. Sluik, B. Buijsse, R. Muckelbauer, R. Kaaks, B. Teucher, N.F. Johnsen, A. Tjønneland, K. Overvad, J.N. Ostergaard, P. Amiano, E. Ardanaz, B. Bendinelli, V. Pala, R. Tumino, F. Ricceri, A. Mattiello, A.M. Spijkerman, E.M. Monninkhof, A.M. May, P.W. Franks, P.M. Nilsson, P. Wennberg, O. Rolandsson, G. Fagherazzi, M.C. Boutron-Ruault, F. Clavel-Chapelon, J.M. Castan˜o, V. Gallo, H. Boeing, U. No¨thlings, Physical activity and mortality in individuals with diabetes mellitus: a prospective study and meta-analysis. Arch. Intern. Med. 172, 1285–1295 (2012) A. Rossi, A. Dikareva, S.L. Bacon, S.S. Daskalopoulou, The impact of physical activity on mortality in patients with high blood pressure: a systematic review. J. Hypertens. 30, 1277–1288 (2012) US Department of Health and Human Services, Physical activity guidelines for Americans (Washington, DC, US Department of Health and Human Services, 2008) A. Onat, H. Ozhan, A.M. Esen, S. Albayrak, A. Karabulut, G. Can, G. Hergenc¸, Prospective epidemiologic evidence of a ‘‘protective’’ effect of smoking on metabolic syndrome and diabetes among Turkish women without associated overall health benefit. Atherosclerosis 193, 380–388 (2007) A. Pietroiusti, A. Neri, G. Somma, L. Coppeta, I. Iavicoli, A. Bergamaschi, A. Magrini, Incidence of metabolic syndrome among night-shift healthcare workers. Occup. Environ. Med. 67, 54–57 (2010)
META-ANALYSIS
Association between leisure time physical activity and metabolic syndrome: a meta-analysis of prospective cohort studies Dan He • Bo Xi • Jian Xue • Pengcheng Huai Min Zhang • Jun Li
•
Received: 24 August 2013 / Accepted: 30 October 2013 Ó Springer Science+Business Media New York 2013
Abstract A great number of prospective studies have investigated the relationship between leisure time physical activity (LTPA) and metabolic syndrome (MetS) risk. However, the results have been inconsistent. The aim of this study was to clarify the relationship between LTPA and MetS risk. Literature databases were searched including PubMed and Embase up to June 2013. A total of 17 studies, including 64,353 participants and 11,271 incident cases, were included in the meta-analysis. A high level of LTPA was statistically associated with decreased risk of MetS [high vs. low: relative risk (RR) = 0.80, 95 % confidence interval (CI) 0.75–0.85], whereas a moderate level of LTPA was weakly associated with decreased risk of MetS (moderate vs. low: RR = 0.95, 95 % CI 0.91–1.00). Subgroup analyses indicated that the association between a moderate level of LTPA and decreased risk of MetS was only significant in men (moderate vs. low: RR = 0.88, 95 % CI 0.81–0.97) and in studies with more than a 10-year follow-up period (moderate vs. low: RR = 0.90, 95 % CI 0.84–0.97). A high level of LTPA was statistically
Dan He and Bo Xi have contributed equally to this work. D. He B. Xi (&) J. Xue M. Zhang J. Li (&) Department of Maternal and Child Health Care, School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan 250012, People’s Republic of China e-mail: [email protected] J. Li e-mail: [email protected] P. Huai Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan, People’s Republic of China
associated with decreased risk of MetS in each subgroup. A higher level of LTPA is associated with a lower risk of MetS. These findings could have public health implications with regard to prevention of MetS through lifestyle interventions. Keywords Metabolic syndrome Leisure time physical activity Prospective study Meta-analysis
Introduction Metabolic syndrome (MetS) is a major public health problem worldwide. MetS is characterized by a clustering of risk factors, including obesity, hypertension, dyslipidemia, hyperglycemia, and hyperinsulinemia [1]. Epidemiological studies have indicated that MetS is associated with increased risk of type 2 diabetes and cardiovascular diseases (CVDs) [2]. Thus, prevention of the MetS is a key public health target. Genetic factors [3], inflammatory factors [4], adipokines [5], dietary patterns, and lifestyle factors [6] are thought to contribute to the pathogenesis of MetS. Previous reviews have commented on the association between leisure time physical activity (LTPA) and risk of MetS [7–9]. However, the evidence was mainly based on findings from crosssectional studies which limited causality inference. Recently, a great number of prospective studies have investigated the relationship between LTPA and MetS risk [10–23]. However, the findings have been inconsistent and no meta-analysis of prospective studies on this topic has been published. The aim of this study was therefore to clarify the relationship between LTPA and MetS risk by combining all related published prospective studies.
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Materials and methods Literature and search strategy Literature databases were searched including PubMed and Embase. The search strategy to identify all possible studies involved the use of the following key words: (physical activity OR PA OR exercise) and (MetS OR MetS 9 OR syndrome 9 OR cardiometabolic risk factor OR insulin resistance syndrome) and (cohort OR prospective OR longitudinal OR follow-up). The reference lists of retrieved articles were hand searched. The literature search was limited to the English language. The literature search was updated on June 20, 2013. Inclusion criteria and data extraction The studies included in the meta-analysis met all the following inclusion criteria: (1) evaluated the association between LTPA and MetS; (2) used prospective design; and (3) provided covariates’ adjusted relative risk (RR) with 95 % confidence interval (CI). The following information was extracted from each study: (1) name of the first author; Fig. 1 Flow chart of metaanalysis for exclusion/inclusion of individual articles (or studies)
(2) year of publication; (3) origin of country; (4) number of incident MetS cases and total population; (5) sex ratio and age of the study population; (6) duration of follow-up; (7) MetS criteria; (8) measurement of LTPA; (9) definition of low, moderate, and high levels of LTPA; and (10) covariates used in adjustment. The two authors independently assessed the articles for compliance with the inclusion/ exclusion criteria and resolved disagreements through discussion. Statistical analysis In this meta-analysis, LTPA was categorized to three levels: low, moderate, and high. The association of LTPA with MetS was estimated by calculating pooled OR and 95 % CI. The significance of pooled OR was determined by Z test (p \ 0.05 was considered statistically significant). A Q test was performed to examine the between-study heterogeneity. A random (DerSimonian–Laird method [24]) or fixed (Mantel–Haenszel method [25]) effects model was used to calculate pooled OR in the presence (p B 0.10) or absence (p [ 0.10) of heterogeneity, respectively. Subgroup analyses were conducted based on
Articles identified through database search (n=1449) Articles excluded: · Obvious irrelevance after titles and abstracts evaluated (n=1401) Articles screened (n =48) Articles excluded: · MS not an outcome (n=8) · PA not an exposure (n=6) · Cross-sectional or case-control design (n=12) · Reviews (n=2) Full-text of the articles accessed for eligibility (n =20 ) Articles excluded: · No RR with 95%CI (n=3) · Total population less than 500 (n=1) · Occupational physical activity (n=2) 14 articles included in the meta-analysis with a total of 17 cohorts*
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*Note: three articles (Wilsgaard et al., 2007;Yang, et al., 2008; Silveira et al., 2010) contained a total of 6 cohorts
28
13.8
USA
UK
Norway
Norway
Carnethon et al. [11]
Wannamethee et al. [12]
Holme et al. [13]
Wilsgaard and Jacobsen [14] (men)
20
13.6
4
Finland
Laaksonen et al. [10]
Followup year
Country
Study
1,169
1,597
790
575
107
No. of MetS cases
Age: 20–61 years
All were men
Total: 8,536
Age: 40–49 years
All were men
Total: 6,410
Age: 60–79 years
All were men
Total: 3,051
Age: 18–30 years
Women: 2,323
Men: 1,869
Total: 4,192
Age: 42–60 years
All were men
Total: 612
Population (sex ratio, age)
NCEP ATPIII
Based on the intensity of LTPA by questionnaire
Based on the intensity, duration, and frequency of LTPA by questionnaire
NCEP ATPIII
Based on the average duration and intensity of LTPA by questionnaire
NCEP ATPIII
Based on the frequency and intensity of LTPA by questionnaire
Based on the duration, frequency, and intensity of LTPA by questionnaire
WHO
NCEP ATPIII
Measurement of LTPA
Definition for MetS
Table 1 Characteristics of prospective studies included in the meta-analysis
High: C7.5 METs
Moderate: 4.5–7.5 METs
Low: \4.5 metabolic equivalents (METs)
High: hard training or competition sports regularly several times a week
Moderate: walking, bicycling, or other forms of physical activity including walking or bicycling to and from the place of work and a Sunday walk totaling at least four hours a week; or exercise, sports, heavy gardening, and similar activities totaling at least 4 h a week
Low: usually reading, watching television, or other sedentary occupations at leisure
Moderate: PA score ranging from 6 to 12 High: PA score more than 13
Low: PA score \5
High: PA score above the median at all four examinations
Moderate: PA score fluctuated around the median at all four examinations
Low: PA score below the median at all four examinations (In 1985, 1992, 1995, 2000)
High: C487 min/week
Alcohol intake, coffee consumption, number of cigarettes smoked, year of education
Age, years of education, glucose, triglycerides, body mass index, treated, hypertension and systolic blood pressure at baseline
Age, social class, smoking, alcohol intake, body mass index, dietary fat, and carbohydrate intake
Age category, BMI, waist-to-hip ratio, use of antihypertensive medications, systolic and diastolic blood pressure, and concentrations of HDL, triglycerides insulin, glucose levels, and family history of diabetes Age, race, sex, weight gain, and physical activity over time, education, baseline BMI, baseline physical activity, smoking status, drinking status, crude fiber, total dietary fat intake, and carbohydrate intake
Low: \270 min/week Moderate: 270–486 min/week
Adjustments
Definition of low, moderate and high levels of LTPA
Endocrine
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Country
Norway
Finland
Finland
USA
Japan
USA
Study
Wilsgaard and Jacobsen [14] (women)
Yang et al. [15] (men)
Yang, et al. [15] (women)
Cheriyath et al. [16]
Li et al. [17]
Peterson et al. [18]
Table 1 continued
123
5
3
6
9
9
13.8
Followup year
299
285
1,970
95
146
965
No. of MetS cases
Age: 70–79 years
Women: 718
Men: 778
Total: 1,496
Age: 35–60 years
Total: 1,897 All were men
Age: 45–64 years
Men: 3,456 Women: 4,398
Total: 7,854
Age: 24–39 years
All were women
Total: 1,099
Age: 24–39 years
All were men
Total: 961
Age: 20–61 years
Total: 8,463 All were women
Population (sex ratio, age)
Based on the intensity, frequency, and duration of LTPA by questionnaire Based on the intensity, frequency, and duration of LTPA by questionnaire Based on the duration and intensity of LTPA by questionnaire
NCEP ATPIII
NCEP ATPIII
NCEP ATPIII
NCEP ATPIII
Based on the duration and frequency of LTPA by questionnaire
Based on the duration, frequency, and intensity of LTPA by questionnaire
Based on the intensity of LTPA by questionnaire
NCEP ATPIII
AHA/ NHLBI
Measurement of LTPA
Definition for MetS
High: walking a minimum of 150 min/week at both year 1 and year 6
Moderate: walking a minimum of 150 min/week at year 1 and \150 min/week at year 6, or walking \150 min/week at year 1 and equal to or[150 min/week at year 6.
Low: walking \150 min/week at year 1 and at year 6
PA 3 days or more and 90 min or more in total per week
Low: not regularly Moderate: moderate or vigorous
High: PA score at the highest tertile (C2.75)
Moderate: PA score at the middle tertile (2.25–2.50)
Low: PA score at the lowest tertile (1.00–2.00)
High: PA index at the highest tertile
Moderate: PA index at the middle tertile
Low: PA index at the lowest tertile
High: PA index at the highest tertile
Moderate: PA index at the middle tertile
Low: PA index at the lowest tertile
High: C7.5 METs
Year 1 body weight, race, education, number of diagnoses, heart disease, and year 1 min/week in highintensity exercise
Age, BMI, Number of healthy eating behaviors, smoking status, weight change since one’s mid-twenties
Baseline age, race, sex, education, smoking, prevalent CHD, total cholesterol, sampling weight, and BMI
Age, smoking, and education
Age, smoking, and education
Alcohol intake, coffee consumption, number of cigarettes smoked, year of education
Low: \4.5 metabolic equivalents (METs) Moderate: 4.5–7.5 METs
Adjustments
Definition of low, moderate and high levels of LTPA
Endocrine
Country
Brazil
Brazil
Finland
Denmark
USA
Study
Silveira et al. [19] (men)
Silveira et al. [19] (women)
Ja¨a¨skela¨inen et al. [20]
Laursen et al. [21]
Bradshaw et al. [22]
Table 1 continued
9
10
27
22
22
Followup year
1,840
585
396
81
132
No. of MetS cases
Age: 54 ± 6 years
Women: 5,517
Men: 3,686
Total: 9,203
Age: 21–98 years
Men: 1,579 Women: 2,389
Total: 3,968
Age: 3–18 years
Women: 1,157
Men: 971
Total: 2,128
All were women
Total: 1,761
Total: 1,834 All were men
Population (sex ratio, age)
NCEP ATPIII
AHA/ NHLBI
Harmonized criteria
NCEP ATPIII
NCEP ATPIII
Definition for MetS
Based on the duration and intensity of LTPA by questionnaire
Based on the frequency, duration, and intensity of LTPA by questionnaire
Based on the frequency and intensity of LTPA by questionnaire
Based on the duration and intensity of LTPA by questionnaire
Based on the duration and intensity of LTPA by questionnaire
Measurement of LTPA
High: PA score more than 2.75
Moderate: PA score from 2 to 2.75
Low: PA score \2
High: light PA [4 or 2–4 h/week of more vigorous PA (e.g., brisk walking, fast biking, heavy gardening work, sport that causes perspiration or exhaustion) or more than 4 h/week of moderate PA or regular heavy exercise or competitive sports several times per week
Moderate: light PA 2–4 h/week
Low: sedentary or light PA (e.g., slow walking/biking, light gardening work) \2 h/week
Moderate: Per unit increase for PA score
High: more than 150 min
Moderate: 10–140 min
Low: \10 min
Age, sex, ethnicity, education, smoking, drinking, energy intake
Age, cohabitation, education, alcohol, smoking, income, duration of schooling, jogging, walking speed and volume
Age, sex, triglycerides, insulin, BMI, systolic blood pressure, HDL cholesterol, family history of hypertension, CRP, family history of diabetes, parents’ education, vegetable consumption, fruit consumption, fish consumption, LDL cholesterol, butter use on bread
Alcohol intake, smoking, low fiber, high fat intake
Alcohol intake, smoking, low fiber, high fat intake
Low: \10 min Moderate: 10–140 min High: more than 150 min
Adjustments
Definition of low, moderate and high levels of LTPA
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123
Age: 16 years
Women: 424
MetS metabolic syndrome, WHO World Health Organization, NCEP ATPIII National Cholesterol Education Program Adult Treatment Panel III, AHA/NHLBI American Heart Association/ National Heart Lung and Blood Institute, and IDF International Diabetes Federation
High: daily
Moderate: several times/week
Sex, socioeconomic disadvantage, family history of diabetes, BMI, intake of sweets/ pastries, alcohol consumption, smoking, and TV viewing/ leisure time physical activity at age 16 years, physical activity at age 43 years Low: less than once a week
Based on the frequency of LTPA by questionnaire IDF Total: 888 Men: 464 239 Sweden Wennberg et al. [23]
27
Country Study
Table 1 continued
Followup year
No. of MetS cases
Population (sex ratio, age)
Definition for MetS
Measurement of LTPA
Definition of low, moderate and high levels of LTPA
Adjustments
Endocrine
sex, duration of follow-up, and definitions of MetS. Sensitivity analysis after excluding one study at a time was performed to assess the stability of the results. Publication bias was assessed by Begg’s test [26] (p \ 0.05 was considered statistically significant). Statistical analysis was conducted using STATA version 11 (StataCorp LP, College Station, TX, USA).
Results Characteristics of the studies A flow chart of meta-analysis for exclusion/inclusion of individual articles (or studies) is presented as Fig. 1. In brief, the literature search identified a total of 1,449 potentially relevant papers. 1,401 papers were excluded after reading the title and abstract because of obvious irrelevance at the first step. Furthermore, 28 articles were excluded because they were reviews, based on cross-sectional or case–control design, did not consider MetS as an outcome, or did not consider LTPA as an exposure. Then, 20 articles met the primary inclusion criteria. However, six articles were further excluded because three articles did not provide RR and 95 % CI, one article included \500 individuals free of MetS at baseline since a study with small sample size usually reports false positive result, and two articles investigated the association between occupational PA and MetS risk. In addition, since the data were provided by sex in each of three papers [14, 15, 19], they were considered as the separate studies in the following data analysis. Therefore, 14 articles with a total of 17 studies (64,353 participants and 11,271 incidence cases) were included in the final meta-analysis [10–23]. Of them, 15 studies used the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII) criteria, the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria, or the Harmonized criteria (these three criteria are uniform) to define MetS; one used the World Health Organization (WHO) criteria; and the rest one used the International Diabetes Federation criteria (IDF) criteria. The characteristics of the included prospective studies are presented in Table 1. Meta-analysis results A moderate level of LTPA was weakly associated with decreased risk of MetS (moderate vs. low: RR = 0.95, 95 % CI 0.91–1.00, Fig. 2), with no evidence of betweenstudy heterogeneity (I2 = 18.3 %, p for heterogeneity = 0.239). A high level of LTPA was statistically associated with decreased risk of MetS (high vs. low: RR = 0.80, 95 % CI 0.75–0.85, Fig. 3), with no evidence
Endocrine
Fig. 2 Meta-analysis of the association between moderate level of LTPA and risk of developing MetS
Fig. 3 Meta-analysis of the association between high level of LTPA and risk of developing MetS
of between-study heterogeneity (I2 = 17.1 %, p for heterogeneity = 0.262). Subgroup analyses by sex, duration of follow-up, and diagnostic criteria were performed. The results indicated that a moderate level of LTPA was statistically associated with decreased risk of MetS in men (moderate vs.
low: RR = 0.88, 95 % CI 0.81–0.97, Table 2) and in studies with a duration of follow-up more than 10 years (moderate vs. low: RR = 0.90, 95 % CI 0.84–0.97, Table 2). A high level of LTPA was statistically associated with decreased risk of MetS in each subgroup (Table 2).
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Endocrine Table 2 Subgroup analysis of the association between LTPA and MetS RR (95 % CI)
Statistical model
I2 (%)
pH
17
0.95 (0.91–1.00)
Fixed
18.3
0.239
8
0.88 (0.81–0.97)
Fixed
6.5
0.380
4
0.99 (0.86–1.14)
Fixed
10.8
0.339
No. of studies Moderate versus low All Sex Men Women
Duration of follow-up \10
7
1.00 (0.94–1.07)
Fixed
37.8
0.140
C10
10
0.90 (0.84–0.97)
Fixed
0.0
0.782
0.96 (0.91–1.01)
Fixed
19.2
0.239
0.76 (0.55–1.04)
Fixed
0.0
0.724
15
0.80 (0.75–0.85)
Fixed
17.1
0.262
7
0.71 (0.63–0.80)
Fixed
0.0
0.941
4
0.68 (0.54–0.85)
Fixed
0.0
0.834
Diagnostic criteria NCEP ATPIIIa Others
15 2
High versus low All Sex Men Women
b
Duration of follow-up \10
6
0.85 (0.79–0.91)
Fixed
32.5
0.192
C10
9
0.71 (0.64–0.78)
Fixed
0.0
0.995
13
0.80 (0.76–0.85)
Fixed
16.8
0.274
2
0.54 (0.34–0.88)
Fixed
0.0
0.971
Diagnostic criteria NCEP ATPIIIa Others
pH, p value for between-study heterogeneity a
AHA/NHLBI or Harmonized criteria Two studies by Li et al. [17] and Ja¨a¨skela¨inen et al. [20] did not provide the RR with 95 % CI for high level of LTPA
b
Sensitivity analyses and publication bias After excluding one study at a time, the sensitivity analyses confirmed the statistical association between a high level of LTPA and decreased risk of MetS [RR with 95 % CI ranging from 0.78 (0.73–0.83) to 0.80 (0.76–0.85)] and the weak association between a moderate level of LTPA and decreased risk of MetS [RR with 95 % CI ranging from 0.92 (0.87–0.98) to 0.96 (0.91–1.01)]. No publication bias was detected for both moderate (p = 0.064) and high (p = 0.729) levels of LTPA.
Discussion To our knowledge, this is the first meta-analysis of prospective cohort studies reporting the association between LTPA and development of MetS. The results indicated that high LTPA was significantly associated with decreased risk
123
of MetS, whereas moderate LTPA was weakly associated with incident MetS compared to those who were inactive, after adjustment for potential confounding factors. In the stratified subgroups, the association between moderate LTPA and MetS was significant in men and in studies with more than a 10-year follow-up period; high LTPA decreased the risk of MetS regardless of sex, duration of follow-up, and the MetS definitions used. To date, 14 articles including a total of 17 prospective studies have examined the association between LTPA and risk of MetS. However, they have revealed conflicting findings. The discrepancy might be due to differences in sex ratio, duration of follow-up, and diagnosis criteria of MetS for each included study. In 2002, Laaksonen et al. [10] firstly reported that high rather than moderate LTPA had a beneficial effect on the risk of MetS in a 4-year follow-up study of 612 middle-aged men without MetS at baseline. The following studies demonstrated either significant [11, 12, 14, 15, 18, 22] or non-significant [13, 16, 19, 21] association for high LTPA. In this study, the pooled RR combining all published prospective studies confirmed the significant association of high LTPA with risk of MetS. To observe whether sex, duration of follow-up, and definition of MetS influence the association between LTPA and MetS risk, we further performed subgroup analyses based on those three variables. The significant association for moderate LTPA was only found in men and in studies with more than a 10-year follow-up period, suggesting the sex-specific effect on the association, and moderate activity might have an effect, but takes longer to show results. Different definitions for MetS have been proposed, including WHO [27], NCEP ATP III [28], IDF [29], AHA/NHLBI [30], and the updated Harmonized definition [31]. These definitions share several characteristics, but on some features, they are different. Indeed, three definitions including NCEP ATP III, AHA/NHLBI, and the updated Harmonized definition are uniform. Thus, the studies using those three criteria were pooled together in the subgroup analysis. The association between LTPA and MetS risk was not influenced by the different definitions used. Several meta-analyses with prospective studies have investigated the association of LTPA with other chronic diseases, including coronary heart disease [32], stroke [33], type 2 diabetes [34], hypertension [35], various types of cancer [36–38], and mortality [39, 40]. These publications showed an association of LTPA with the diseases and mortality, which was similar to our finding. That is, LTPA is beneficial for prevention and control of many chronic diseases. Public health guidelines for weekly physical activity recommend accumulating a minimum of 150 min/ week of moderate intensity physical activity (such as brisk walking) [41]. Our results highlight the need to target
Endocrine
LTPA, especially high LTPA, to prevent the development of MetS in the general population. Our study has several major strengths. First, all included studies were prospective population based, enabling us to investigate the causal inference between LTPA and MetS. Second, the statistical power of the study was reasonably high since it included more than 10,000 incident cases. Third, we used covariates’ adjusted RRs with 95 % CIs from individual studies to get the pooled estimate, which had ruled out the effect of confounding factors on the association. However, three limitations of the present study should be noted. First, LTPA was self-reported in all the included studies, which may affect its precision as a predictor. Second, the definitions of low, moderate, and high LTPA were different among the included studies. Third, we studied only LTPA, not occupational PA since only two prospective studies have investigated the association between occupational PA and development of MetS [42, 43]. Actually, both studies showed the protective effect of occupational PA with risk of MetS. In conclusion, a higher level of LTPA is associated with a lower risk of MetS. Individuals should be recommended to take part in regular high LTPA to prevent the risk of developing MetS and related type 2 diabetes and CVDs. Acknowledgments This work was supported by the Research Fund for the Doctoral Program of Higher Education of China (20120131120004). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Conflict of interest
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
None. 17.
References 18. 1. E.A. Gale, The myth of the metabolic syndrome. Diabetologia 48, 1679–1683 (2005) 2. P.W. Wilson, R.B. D’Agostino, H. Parise, L. Sullivan, J.B. Meigs, Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 112, 3066–3072 (2005) 3. J.H. Zhang, N.F. Li, Z.T. Yan, L. de Zhang, H.M. Wang, Y.Y. Guo, Z. Ling, Association of genetic variations of PRDM16 with metabolic syndrome in a general Xinjiang Uygur population. Endocrine 41, 539–541 (2012) 4. T. Yang, C.H. Chu, P.C. Hsieh, C.H. Hsu, Y.C. Chou, S.H. Yang, C.H. Bai, S.L. You, L.C. Hwang, T.C. Chung, C.A. Sun, C-reactive protein concentration as a significant correlate for metabolic syndrome: a Chinese population-based study. Endocrine 43, 351–359 (2013) 5. T. Stefanov, M. Blu¨her, A. Vekova, I. Bonova, S. Tzvetkov, D. Kurktschiev, T. Temelkova-Kurktschiev, Circulating chemerin decreases in response to a combined strength and endurance training. Endocrine (2013). doi:10.1007/s12020-013-0003-2 6. C.H. Tsai, T.C. Li, C.C. Lin, H.S. Tsay, Factor analysis of modifiable cardiovascular risk factors and prevalence of
19.
20.
21.
22.
metabolic syndrome in adult Taiwanese. Endocrine 40, 256–264 (2011) S. Carroll, M. Dudfield, What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome. Sports Med. 34, 371–418 (2004) B.C. Guinhouya, H. Samouda, D. Zitouni, C. Vilhelm, H. Hubert, Evidence of the influence of physical activity on the metabolic syndrome and/or on insulin resistance in pediatric populations: a systematic review. Int. J. Pediatr. Obes. 6, 361–388 (2011) J.R. Churilla, R.F. Zoeller, Physical activity: physical activity and the metabolic syndrome: a review of the evidence. AJLM 2, 118–125 (2008) D.E. Laaksonen, H.M. Lakka, J.T. Salonen, L.K. Niskanen, R. Rauramaa, T.A. Lakka, Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome. Diabetes Care 25, 1612–1618 (2002) M.R. Carnethon, C.M. Loria, J.O. Hill, S. Sidney, P.J. Savage, K. Liu, Coronary Artery Risk Development in Young Adults study, Risk factors for the metabolic syndrome: the Coronary Artery Risk Development in Young Adults (CARDIA) study, 1985–2001. Diabetes Care 27, 2707–2715 (2004) S.G. Wannamethee, A.G. Shaper, P.H. Whincup, Modifiable lifestyle factors and the metabolic syndrome in older men: effects of lifestyle changes. J. Am. Geriatr. Soc. 54, 1909–1914 (2006) I. Holme, S. Tonstad, A.J. Sogaard, P.G. Larsen, L.L. Haheim, Leisure time physical activity in middle age predicts the metabolic syndrome in old age: results of a 28-year follow-up of men in the Oslo study. BMC Public Health 7, 154 (2007) T. Wilsgaard, B.K. Jacobsen, Lifestyle factors and incident metabolic syndrome. The Tromsø Study 1979-2001. Diabetes Res. Clin. Pract. 78, 217–224 (2007) X. Yang, R. Telama, M. Hirvensalo, N. Mattsson, J.S. Viikari, O.T. Raitakari, The longitudinal effects of physical activity history on metabolic syndrome. Med. Sci. Sports Exerc. 40, 1424–1431 (2008) P. Cheriyath, Y. Duan, Z. Qian, L. Nambiar, D. Liao, Obesity, physical activity and the development of metabolic syndrome: the atherosclerosis risk in communities study. Eur. J. Cardiovasc. Prev. Rehabil. 17, 309–313 (2010) Y. Li, H. Yatsuya, H. Iso, K. Tamakoshi, H. Toyoshima, Incidence of metabolic syndrome according to combinations of lifestyle factors among middle-aged Japanese male workers. Prev. Med. 51, 118–122 (2010) M.J. Peterson, M.C. Morey, C. Giuliani, C.F. Pieper, K.R. Evenson, V. Mercer, M. Visser, J.S. Brach, S.B. Kritchevsky, B.H. Goodpaster, S. Rubin, S. Satterfield, E.M. Simonsick, Health ABC Study, Walking in old age and development of metabolic syndrome: the health, aging, and body composition study. Metab. Syndr. Relat. Disord. 8, 317–322 (2010) V.M. Silveira, B.L. Horta, D.P. Gigante, M.R. Azevedo, Metabolic syndrome in the 1982 Pelotas cohort: effect of contemporary lifestyle and socioeconomic status. Arq. Bras. Endocrinol. Metabol. 54, 390–397 (2010) P. Ja¨a¨skela¨inen, C.G. Magnussen, K. Pahkala, V. Mikkila¨, M. Ka¨ho¨nen, M.A. Sabin, M. Fogelholm, N. Hutri-Ka¨ho¨nen, L. Taittonen, R. Telama, T. Laitinen, E. Jokinen, T. Lehtima¨ki, J.S. Viikari, O.T. Raitakari, M. Juonala, Childhood nutrition in predicting metabolic syndrome in adults: the cardiovascular risk in Young Finns Study. Diabetes Care 35, 1937–1943 (2012) A.H. Laursen, O.P. Kristiansen, J.L. Marott, P. Schnohr, E. Prescott, Intensity versus duration of physical activity: implications for the metabolic syndrome. A prospective cohort study. BMJ Open 2, e001711 (2012) P.T. Bradshaw, K.L. Monda, J. Stevens, Metabolic syndrome in healthy obese, overweight, and normal weight individuals: the
123
Endocrine
23.
24. 25.
26.
27.
28.
29.
30.
31.
32.
atherosclerosis risk in communities study. Obesity (Silver Spring) 21, 203–209 (2013) P. Wennberg, P.E. Gustafsson, D.W. Dunstan, M. Wennberg, A. Hammarstro¨m, Television viewing and low leisure-time physical activity in adolescence independently predict the metabolic syndrome in mid-adulthood. Diabetes Care 36, 2090–2097 (2013) R. DerSimonian, N. Laird, Meta-analysis in clinical trials. Control Clin. Trials 7, 177–188 (1986) N. Mantel, W. Haenszel, Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl Cancer Inst. 22, 719–748 (1959) C.B. Begg, M. Mazumdar, Operating characteristics of a rank correlation test for publication bias. Biometrics 50, 1088–1101 (1994) K.G. Alberti, P.Z. Zimmet, Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation. Diabet. Med. 15, 539–553 (1998) S.M. Grundy, H.B. Brewer, J.I. Cleeman, S.C. Smith, C. Lenfant, American Heart Association; National Heart, Lung, and Blood Institute, Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 109, 433–438 (2004) The IDF consensus worldwide definition of the metabolic syndrome. http://www.idf.org/webdata/docs/MetS_def_update2006. pdf.(2006).Accessed 14 Nov 2013 S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J. Gordon, R.M. Krauss, P.J. Savage, S.C. Smith, J.A. Spertus, F. Costa, American Heart Association; National Heart, Lung, and Blood Institute, Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung and Blood Institute scientific statement. Circulation 112, 2735–2752 (2005) K.G. Alberti, R.H. Eckel, S.M. Grundy, P.Z. Zimmet, J.I. Cleeman, K.A. Donato, J.C. Fruchart, W.P. James, C.M. Loria, S.C. Smith, International Diabetes Federation TaskForce on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity, Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120, 1640–1645 (2009) J. Sattelmair, J. Pertman, E.L. Ding, H.W. Kohl, W. Haskell, I.M. Lee, Dose response between physical activity and risk of
123
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
coronary heart disease: a meta-analysis. Circulation 124, 789–795 (2011) J. Li, J. Siegrist, Physical activity and risk of cardiovascular disease–a meta-analysis of prospective cohort studies. Int. J. Environ. Res. Public Health 9, 391–407 (2012) C.Y. Jeon, R.P. Lokken, F.B. Hu, R.M. van Dam, Physical activity of moderate intensity and risk of type 2 diabetes: a systematic review. Diabetes Care 30, 744–752 (2007) P. Huai, H. Xun, K.H. Reilly, Y. Wang, W. Ma, B. Xi, Physical activity and risk of hypertension: a meta-analysis of prospective cohort studies. Hypertension (2013). doi:10.1161/HYPERTENSIONAHA. 113.01965 Y. Je, J.Y. Jeon, E.L. Giovannucci, J.A. Meyerhardt, Association between physical activity and mortality in colorectal cancer: a meta-analysis of prospective cohort studies. Int. J. Cancer (2013). doi:10.1002/ijc.28208 Y. Wu, D. Zhang, S. Kang, Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res. Treat. 137, 869–882 (2013) J.Y. Sun, L. Shi, X.D. Gao, S.F. Xu, Physical activity and risk of lung cancer: a meta-analysis of prospective cohort studies. Asian Pac. J. Cancer Prev. 13, 3143–3147 (2012) D. Sluik, B. Buijsse, R. Muckelbauer, R. Kaaks, B. Teucher, N.F. Johnsen, A. Tjønneland, K. Overvad, J.N. Ostergaard, P. Amiano, E. Ardanaz, B. Bendinelli, V. Pala, R. Tumino, F. Ricceri, A. Mattiello, A.M. Spijkerman, E.M. Monninkhof, A.M. May, P.W. Franks, P.M. Nilsson, P. Wennberg, O. Rolandsson, G. Fagherazzi, M.C. Boutron-Ruault, F. Clavel-Chapelon, J.M. Castan˜o, V. Gallo, H. Boeing, U. No¨thlings, Physical activity and mortality in individuals with diabetes mellitus: a prospective study and meta-analysis. Arch. Intern. Med. 172, 1285–1295 (2012) A. Rossi, A. Dikareva, S.L. Bacon, S.S. Daskalopoulou, The impact of physical activity on mortality in patients with high blood pressure: a systematic review. J. Hypertens. 30, 1277–1288 (2012) US Department of Health and Human Services, Physical activity guidelines for Americans (Washington, DC, US Department of Health and Human Services, 2008) A. Onat, H. Ozhan, A.M. Esen, S. Albayrak, A. Karabulut, G. Can, G. Hergenc¸, Prospective epidemiologic evidence of a ‘‘protective’’ effect of smoking on metabolic syndrome and diabetes among Turkish women without associated overall health benefit. Atherosclerosis 193, 380–388 (2007) A. Pietroiusti, A. Neri, G. Somma, L. Coppeta, I. Iavicoli, A. Bergamaschi, A. Magrini, Incidence of metabolic syndrome among night-shift healthcare workers. Occup. Environ. Med. 67, 54–57 (2010)
