Lifestyle interventions for preventing type 2 diabetes mellitus
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effects of lifestyle intervention programmes (diet and/or exercise) for preventing type 2 diabetes mellitus in groups of individuals at risk and in the general population. The present review will address specifically the effects of interventions aimed at modifying dietary behaviour and physical activity.
Background
TYPE 2 DIABETES MELLITUS
Type 2 diabetes mellitus is the most common type of diabetes. In Western countries the disease affects up to 7% of the population (Harris 1998, WHO 1994). Its incidence is associated with the 'Westernised lifestyle', mainly in terms of dietary habits and physical activity (ADA 1996). Special attention is to be paid to the increasing incidence of the disease in newly industrialized and developing countries in which lifestyle changes have occurred (WHO 1994). Also, an increasing incidence in adolescents, especially in the US, has been shown particularly in the non‐white population (Rosenbloom 1999). Obesity and decreased physical activity are associated with the development of glucose intolerance and type 2 diabetes (Eriksson 1991). The events leading to the development of the disease are mainly an abnormal insulin secretion and insulin resistance. Thus, an insufficient insulin secretion combined with a reduced capacity of peripheral tissues to utilise glucose and an increased glucose production by the liver leads to the progressive development of hyperglycaemia (Lillioja 1993). However, the exact sequence of events leading to the development of the disorder is still to be fully characterised. As the progression from normoglycaemia to overt hyperglycaemia is slow, a significant proportion of individuals remain undiagnosed during the initial period of the disease. A majority of individuals later developing the disease present with obesity, which further contributes to an increased insulin resistance (Beck‐Nielsen 2000). Other known factors are also associated with the appearance of the disease, for example increasing age and lack of physical activity. As there is a strong familial predisposition, first‐degree relatives of known type 2 diabetic patients are at increased risk of developing the disorder (Rewers 1995).
NON‐PHARMACOLOGIC INTERVENTIONS IN THE TREATMENT OF TYPE 2 DIABETES MELLITUS
The management of the disease involves non‐pharmacological as well as pharmacological approaches. For a detailed overview of diabetes mellitus and its treatment, please see under 'Additional information' in the information on the Metabolic and Endocrine Disorders Group on the Cochrane Library (see 'About the Cochrane Collaboration', 'Collaborative Review Groups').
It has been shown that weight reduction and an increase in daily energy expenditure decrease insulin resistance and increase glucose tolerance (Ross 2000). Indeed, advice on diet and exercise are an important part of the treatment of type 2 diabetes. Nutritional advice usually consists of caloric restriction if the patient is overweight, low total fat content (especially saturated fat) and high (predominantly unrefined) carbohydrate content. It may be hypothesised that interventions aimed at preventing the development of obesity and at increasing physical activity will lower the incidence of type 2 diabetes in those individuals at risk and probably in the general population. Further, the adoption of a healthy lifestyle, i.e. avoiding being overweight and exercising regularly, may provide a protective effect against other elements of the metabolic syndrome usually associated with impaired glucose tolerance and type 2 diabetes mellitus, such as hypertension and hyperlipidaemia, which may subsequently increase morbidity and mortality from cardiovascular disease (Stamler 1999; Stampfer 2000).
DIET AND EXERCISE AS PREVENTIVE MEASURES
Primary prevention covers the activities aimed at preventing diabetes from occurring in susceptible individuals or in general population. This can be done through modification of environmental and/or behavioural determinants (e.g. dietary habits), or by any specific intervention (e.g. pharmacological). In the present review, we include diet and exercise interventions under the term 'lifestyle interventions'.
We are not aware of any systematic reviews addressing the subject of the present review. Randomised controlled trials addressing the question of this review are scarce. There are prospective cohort studies that have shown that increased physical activity, independently of other risk factors, has a protective effect against the development of type 2 diabetes (Helmrich 1991; Manson 1992). These epidemiological prospective studies demonstrated that various levels of regular physical activity one to several times a week were associated with a decreased incidence of the disease at long‐term follow‐up (14 and 5 years respectively) in both men and women of different age groups (Helmrich 1991; Manson 1992).
In a recent randomised controlled trial, the Da Qing study, diet and/or exercise interventions were shown to produce a 31 to 46% reduction in the incidence of diabetes during a period of six years in those with impaired glucose tolerance (Pan 1997). There are currently two on‐going large randomised controlled trials which, among other interventions, seek to evaluate the effect of lifestyle modification strategies for the prevention of type 2 diabetes in people with impaired glucose tolerance. The Diabetes Prevention Program (DPP 1999), which is planned to be completed in 2002, is a multicentre randomised controlled trial in the United States with three intervention arms: lifestyle intervention (diet and exercise), metformin and placebo. The Diabetes Prevention Study (DPS 1999) in Finland investigates the efficacy of diet (with the aim of reducing body weight and the intake of saturated fat, and increasing dietary fibre) and exercise (increasing the level of physical activity) for the prevention of type 2 diabetes, as compared to a control group. Study participants in both trials are individuals with impaired glucose tolerance as diagnosed by a 75 gram ‐ oral glucose tolerance test, belonging to different age and ethnic groups (Finnish population, and people from the United States from various ethnic origins).
Our aim is therefore to summarise the evidence regarding lifestyle interventions for preventing type 2 diabetes mellitus in a systematic way.
Objectives
To assess the effects of lifestyle intervention programmes (diet and/or exercise) for preventing type 2 diabetes mellitus in groups of individuals at risk and in the general population. The present review will address specifically the effects of interventions aimed at modifying dietary behaviour and physical activity.
Methods
Criteria for considering studies for this review
Types of studies
Prevention studies could be aimed at high risk groups for developing type 2 diabetes mellitus (see next section) or at the general population. Study design and intervention strategies may be different between such groups. Therefore types of studies to be considered will be different according to the type of participants:
1. High risk groups for the development of type 2 diabetes: Only randomised controlled trials will be considered. Randomisation of individuals or of larger groups will be accepted, as long as a minimum of six groups were randomised.
2. General population: Although randomised controlled trials should be the 'gold standard', authors recognise the possibility of not finding such a design for general population prevention studies; therefore the review will include data from 'controlled before‐and‐after studies' and 'interrupted time series'. According to the methods published by the Cochrane Effective Practice and Organization Care Group, a controlled before‐and‐after study is defined as a design where there is contemporaneous data collection before and after the intervention and an appropriate control site or activity, and an interrupted time series is defined as a design where there is a clearly defined point in time when the intervention occurred and at least three data points before and three after the intervention.
Studies in which the intervention is not specifically aimed at type 2 diabetes prevention, but for prevention of any other related disorders will also be included as long as data on type 2 diabetes prevalence before and after the intervention are available.
Types of participants
1. High risk groups for development of type 2 diabetes mellitus ‐
Participants of any age, sex or ethnicity belonging to any of the major risk groups for the development of type 2 diabetes (ADA 1999):
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Impaired glucose tolerance according to the World Health Organisation criteria (WHO 1985).
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Impaired fasting glucose according to the American Diabetes Association criteria (ADA 1997).
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Previous gestational diabetes.
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Hypertension equal to or greater than 140/90.
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Family history of type 2 diabetes in first degree relatives.
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Obesity (i.e. body mass index equal or greater than 27 kg/m2).
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Dyslipidemia (i.e. HDL cholesterol equal or less than 35 mg/dl and/or triglycerides equal or more than 250 mg/dl).
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High risk ethnic groups (e.g. African‐Americans, Hispanic‐Americans, native Americans, Asian‐Americans, Pacific Islanders).
2. Adult general population.
Types of interventions
Main intervention: Programme designed to improve dietary habits (i.e. to promote weight loss or changes in the composition of the diet) and/or to increase to any degree the level of physical activity.
Comparison interventions:
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No intervention.
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Standard recommendations, defined as general instructions not included in a formal individual or group programme.
Types of outcome measures
MAIN OUTCOME MEASURE
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Development of type 2 diabetes. Ideally, the diagnostic criteria for type 2 diabetes mellitus should have been described in the trial. To be consistent with changes in classification and diagnostic criteria of the disease through the years, the diagnosis should have been established using the standard criteria valid at the time of the beginning of the trial. Changes in the diagnostic criteria may have produced significant variability in the clinical characteristics of the patients included as well as in the results obtained. These differences will be considered and explored in a sensitivity analysis.
ADDITIONAL OUTCOME MEASURES
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Development of impaired glucose tolerance [plasma glucose 2 hours after a 75 g oral glucose load equal or greater than 140 mg/dl and less than 200 mg/dl (WHO 1985)].
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Development of impaired fasting glucose [fasting plasma glucose equal or greater than 110 mg/dl and less than 126 mg/dl (ADA 1997)].
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Mortality.
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Development of cardiovascular events (myocardial infarction either fatal or non‐fatal and angina).
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Anthropometric measures: body weight or body mass index and waist‐to‐hip‐ratio.
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Systolic and diastolic blood pressure.
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Lipid levels: cholesterol, triglycerides and HDL cholesterol.
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Quality of life, ideally measured with a validated instrument.
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Adverse effects (e.g. traumatic injuries secondary to leisure physical activity, nutritional deficits...).
TIMING OF OUTCOME ASSESSMENT
All studies will be required to observe participants for a minimum of one year, which may refer to the intervention itself or to a combination of the intervention with a follow‐up phase. The start of the one year period refers to the start of the intervention.
Search methods for identification of studies
All three investigators will develop the search strategy.
ELECTRONIC SEARCHES
The following electronic medical databases will be searched:
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The Cochrane Library (2001, first issue), including the Cochrane Controlled Trials Register (CCTR) and the Database of Abstracts of Reviews of Effectiveness (DARE) using the search terms for type 2 diabetes and related conditions, lifestyle interventions and primary prevention given in the Medline search strategy below.
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Medline search form 1966 to the 31st of March 2001, as follows:
NOTES: Unless otherwise stated, search terms are free text terms; MeSH: Medical subject heading (Medline medical index term); an asterisk stands for 'any character(s)'
TYPE 2 DIABETES MELLITUS AND RELATED CONDITIONS
1 "DIABETES‐MELLITUS,‐NON‐INSULIN‐DEPENDENT"/ [MeSH term, all subheadings included]
2 "INSULIN‐RESISTANCE"/ [MeSH term, all subheadings included]
3 "OBESITY‐IN‐DIABETES"/ [MeSH term, all subheadings included]
4 (MODY or DM2 or NIDDM or IIDM) [in title or abstract]
5 (non insulin* depend* or noninsulin* depend* or noninsulin?depend* or non insulin?depend*) [in title or abstract]
6 ((typ* "2" or typ* II) near (diabet* or DM)) [in title or abstract]
7 ((keto* resist* or nonketo* or non keto* or adult* onset or matur* onset or late* onset or slow onset or stabl*) near (diabet* or DM or DM2)) [in title or abstract]
8 (insulin* defic* near relativ*) [in title or abstract]
9 (metabolic* syndrom*) [in title or abstract]
10 ((syndrom* X) not ((fragil* X) or (X linked))) [in title or abstract]
11 (plurimetabolic* syndrom* or pluri metabolic* syndrom*) [in title or abstract]
12 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11
13 "DERMATOMYOSITIS"/ [MeSH term, all subheadings included]
14 "MYOTONIC‐DYSTROPHY"/ [MeSH term, all subheadings included]
15 explode "DIABETES‐INSIPIDUS"/ [MeSH term, all subheadings and subtrees included]
16 mellitus [in title or abstract]
17 #15 not (#1 or #16)
18 (diabet* near (insipidus not mellitus)) [in title or abstract]
19 #13 or #14 or #17 or #18
20 #12 not #19
21 "PREDIABETIC‐STATE"/ [MeSH term, all subheadings included]
22 ((prediabet* or pre diabet*) near state) [in title or abstract]
23 explode "PREGNANCY‐IN‐DIABETES"/ [MeSH term, all subheadings and subtrees included]
24 (pregnan* near diabet*) [in title or abstract]
25 "GLUCOSE‐INTOLERANCE"/ [MeSH term, all subheadings included]
26 (impaired glucose tolerance or glucose intoleran* or insulin* resist*) [in title or abstract]
27 (obes* or overweight or over weight) [in title or abstract]
28 "HYPERINSULINEMIA"/ [MeSH term, all subheadings included]
29 (hyperinsulin* or hyper insulin*) [in title or abstract]
30 explode "HYPERLIPIDEMIA"/ [MeSH term, all subheadings and subtrees included]
31 (hyperlipid* or hyper lipid* or d?slipid*) [in title or abstract]
32 "RISK‐FACTORS" [MeSH term]
33 #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32
34 #12 or #33
LIFESTYLE INTERVENTIONS
35 explode "LIFE‐STYLE"/ [MeSH term, all subheadings and subtrees included]
36 (life style or lifestyle) [in title or abstract]
37 explode "HEALTH‐BEHAVIOR"/ [MeSH term, all subheadings and subtrees included]
38 "HEALTH‐PROMOTION"/ [MeSH term, all subheadings included]
39 explode "HEALTH‐EDUCATION"/ [MeSH term, all subheadings and subtrees included]
40 (health* near (behav* or educ* or promot*)) [in title or abstract]
41 explode "SPORTS"/ [MeSH term, all subheadings and subtrees included]
42 explode "EXERTION"/ [MeSH term, all subheadings and subtrees included]
43 explode "EXERCISE‐THERAPY"/ [MeSH term, all subheadings and subtrees included]
44 "PHYSICAL‐FITNESS"/ [MeSH term, all subheadings included]
45 explode "PHYSICAL‐EDUCATION‐AND‐TRAINING"/ [MeSH term, all subheadings and subtrees included]
46 (exercis* or physic* activ* or exert* or physic* fit* or sport*) [in title or abstract]
47 (walk* or jog* or swim* or bicyc* or cycling or weight lift* or gymnastic* or danc*) [in title or abstract]
48 ((strength or resistance or circuit or enduran* or aerob* or physic* or fit*) near train*) [in title or abstract]
49 explode "NUTRITION"/ [MeSH term, all subheadings and subtrees included]
50 explode "DIET‐THERAPY"/ [MeSH term, all subheadings and subtrees included]
51 explode "FEEDING‐BEHAVIOR"/ [MeSH term, all subheadings and subtrees included]
52 (nutrit* or diet* or food* or eat*) [in title or abstract]
53 #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 or #49 or #50 or #51 or #52
PREVENTION
54 explode "PREVENTIVE‐MEDICINE"/ [MeSH term, all subheadings and subtrees included]
55 explode "DIABETES‐MELLITUS"/ [MesH term, subheading prevention‐and‐control]
56 explode "PREVENTIVE‐HEALTH‐SERVICES"/ [MeSH term, all subheadings and subtrees included]
57 (prevent* or prophyla* or avoid*) [in title or abstract]
58 #54 or #55 or #56 or #57
TYPE 2 DIABETES MELLITUS AND RELATED CONDITIONS AND LIFESTYLE INTERVENTIONS AND PREVENTION
59 #34 and #53 and #58
CLINICAL TRIALS
60 See Metabolic and Endocrine Disorders Group search strategy
TYPE 2 DIABETES MELLITUS AND RELATED CONDITIONS AND LIFESTYLE INTERVENTIONS AND PREVENTION AND CLINICAL TRIALS
61. #59 and #60
The following additional databases will be searched, adapting the search strategy given above:
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Cinhal from 1982 to 31st March 2001.
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Embase from 1974 to 31st March 2001.
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Databases of ongoing trials according to the information provided by the editorial base of the Cochrane Metabolic and Endocrine Disorders Group.
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Lilacs from 1982 to 31st March 2001.
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HealthStar from 1975 to 31st March 2001.
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SocioFile from 1974 to 31st March 2001
HANDSEARCHING
We will try to identify additional studies by searching the reference lists of relevant trials and of reviews identified using the same search strategy as in steps 1‐59, combined with the Metabolic and Endocrine Disorders Group's search strategy for identifying systematic reviews and meta‐analyses.
OTHER SEARCH STRATEGIES
Authors of identified studies will be contacted in order to obtain additional references and unpublished or ongoing trials.
Studies in any language will be included.
Data collection and analysis
1. SELECTION OF TRIALS
The total number of studies identified with the searching strategy will be divided into three groups. Three reviewers will independently review the titles, abstracts and keywords of every study identified. Each reviewer will evaluate two of the three groups and each study will be evaluated independently by two of the three reviewers. Full articles will be retrieved for further assessment if the information obtained suggests that the study is prospective and evaluates lifestyle intervention and records development of diabetes. If there is doubt regarding the suitability of the article for inclusion (as judged from title and abstract) full articles will also be retrieved. The agreement between reviewers will be measured using Cohen's kappa. In case of disagreement the third reviewer who initially did not evaluate the study will review it to reach a final decision between the three reviewers.
2. QUALITY ASSESSMENT OF TRIALS
Quality assessment of all included studies will be performed independently by two reviewers (GGP, JMGC). The quality of the included trials will be assessed in terms of the randomisation process and internal and external validity according to the Jadad scale (Jadad 1996) and to the Schulz scale (Schulz 1995). Because it is not possible to perform trials on lifestyle interventions (diet and/or exercise) in a double‐blind design, studies will be evaluated according to the following criteria:
1. Minimisation of selection bias:
a) was the randomisation procedure adequate ?
b) was the allocation concealment adequate ?
2. Minimisation of attrition bias:
a) were withdrawals and dropouts completely described ?
b) was an analysis by intention‐to‐treat performed ?
3. Minimisation of detection bias:
a) Were the outcome assessors blind to the intervention ?
According to the Cochrane handbook, the studies will be broadly classified as A (all criteria met, low risk of bias), B (one or more criteria only partially met; moderate risk of bias) or C (one or more criteria not met; high risk of bias). Considering the quality scoring of the studies included, a sensitivity analysis will be performed. Interrater agreement between the two reviewers will be assessed using Cohen's kappa. When differences in opinion between these two reviewers are found, a third reviewer (DM) will evaluate the study to reach a final decision between the three reviewers.
3. DATA EXTRACTION
For the included studies, the following data will be extracted:
1. General information: title, authors, contact address, published/unpublished, duplicate publication, language of publication, year of publication, sponsoring, setting.
2. Trial characteristics: trial design, duration, randomisation, allocation concealment and method of allocation concealment, was a power analysis performed?
3. Intervention: description, duration, comparisons, co‐interventions.
4. Participants: inclusion and exclusion criteria, total number and number in comparison groups, similarity of groups at baseline with respect to risk conditions for type 2 diabetes development (see types of participants), age, sex, comorbidity, concurrent medication, compliance assessment, withdrawals (number per group and reason of withdrawal); losses to follow‐up (number per group and reason of loss of follow‐up), intention‐to‐treat analysis, subgroups of participants evaluated according to risk conditions for type 2 diabetes development (see types of participants).
5. Primary and secondary outcomes (specified above). This information would be also obtained for the different subgroups evaluated.
A template data extraction form will be developed and it will be tested in a pilot study. Data extraction and data entry will be performed independently in duplicate by two evaluators (GGP, JMGC). Differences in data extraction will be resolved by consensus with the third reviewer (DM), referring back to the original article. If any data are missing in a published report (see data extraction list), the reviewers will contact the first author using the standard letter from the Editorial Base.
4. DATA ANALYSIS
If data are available, of sufficient quality and sufficiently similar, they will be summarised in a meta‐analysis.
The following comparisons will be analysed:
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Lifestyle intervention (diet, exercise or both) versus standard recommendations.
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Lifestyle intervention versus no intervention.
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Diet versus exercise.
Statistical analyses will be carried out using MetaView 4.1 software within Review Manager 4.1. On continuous outcomes, weighted mean differences and 95 % confidence intervals will be calculated. If results for some continuous outcomes are found on different scales and cannot be converted to a standard scale, standardised mean differences will be used. The effect sizes for dichotomous data will be expressed as relative risks (intervention/control). The absolute risk reduction will be also evaluated and used to estimate the number needed to treat (NNT) for each comparison taking into account times of follow‐up. If information is provided in the article we will perform an intention‐to‐treat analysis.
All data will initially be analysed with a random effects model. The chi‐square test for homogeneity will be performed (level of significance p<0.1) to determine whether the distribution of the results is compatible with the assumption that intertrial differences are attributable to chance variation alone. If heterogeneity is found, possible sources of heterogeneity will be assessed by subgroup and sensitivity analyses as described below.
4.1. SENSITIVITY ANALYSES
Sensitivity analyses will take into account the influence of the following factors on effect size:
1. Repeating the analysis to explore the influence of study quality, as described above.
2. Repeating the analysis excluding very large or long studies to evaluate how much they influence the results.
3. Repeating the analysis excluding trials supported by industry.
The robustness of the analysis will be explored further by repeating the analysis using different measures of effects size (relative risk, risk difference) and different statistic models (fixed and random effects models).
4.2. SUBGROUP ANALYSES
Subgroup analyses will be performed, if feasible, to assess whether some groups of subjects at risk for type 2 diabetes could obtain more benefit from the lifestyle intervention than others. Subgroups will be analysed according to risk factors for diabetes mellitus (impaired glucose tolerance, abnormal fasting glucose, previous gestational diabetes, family history of type 2 diabetes, obesity, dyslipidemia, hypertension, high risk ethnic groups). Additionally, sex and age subgroups will be analysed. Finally different types of diets (e.g. weight reduction versus emphasis on 'healthy eating') or exercise schedules (e.g. daily exercise versus twice a week exercise, types of exercise) will be also considered in the subgroup analysis
5. PUBLICATION BIAS
Publication bias will be assessed by using a funnel plot, whereby effect estimates of the common outcome measure are plotted against trial sample size. The funnel plot will be examined visually and tested for symmetry by using a regression method developed by Egger (Egger 1997).
