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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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Are metabolically healthy overweight and obesity benign conditions? A systematic review and meta analysis

, , and .

Review published: .

CRD summary

This generally well-conducted review found that metabolically healthy obese people were at an increased risk of cardiovascular events and death from any cause, in the long term (10 years), compared with metabolically healthy people of normal weight. This conclusion was based on one subgroup analysis, and may be too strong given the less conclusive results from the other analyses.

Authors' objectives

To investigate the effect of metabolic status on all-cause mortality and cardiovascular events in normal weight, overweight and obese people.

Searching

MEDLINE, EMBASE and abstracts from relevant endocrinology meetings were searched for articles from 1950 to June 2013, without language restrictions. Search terms were presented. Reference lists from identified articles were searched.

Study selection

Prospective or cross-sectional cohort studies in adults were eligible. Studies had to categorise people as normal weight, overweight or obese, and categorise their metabolism as healthy or unhealthy. Studies had to report all-cause mortality, or fatal or non-fatal cardiovascular events, as outcomes.

The average participant age ranged from 44 to 70 years. Two studies included only women, and one included only men. Where reported, the rates of smoking ranged from 10% to 51.5%. Three studies included some people (up to 37%) with a history of cardiovascular disease. Metabolic health was categorised as the presence or absence of metabolic syndrome, as defined by the Adult Treatment Panel III or International Diabetes Federation criteria.

Two reviewers selected studies for inclusion, with a third resolving disagreements.

Assessment of study quality

Study quality was assessed using the Newcastle-Ottawa scale, which ranged from 0 (low quality) to 9 (high quality). The number of reviewers who performed the quality assessment was not stated.

Data extraction

The numbers of deaths or cardiovascular events (or risk estimates from survival curves) for different obesity and metabolic health groups were extracted to calculate relative risks and their 95% confidence intervals. Healthy normal-weight participants were used as the reference group. The results without adjustments were extracted.

Two reviewers independently extracted the data; study authors were contacted for further data, where necessary.

Methods of synthesis

Relative risks were pooled using random-effects meta-analysis. Cochran Q and Ι² were used to assess statistical heterogeneity; Ι² over 50% was taken to indicate moderate to high heterogeneity.

Sensitivity analyses and meta-regressions were used to investigate the causes of any heterogeneity. Publication bias was assessed using funnel plots and the Peters test.

Results of the review

Twelve studies (eight prospective and four cross-sectional observational) met the inclusion criteria, but the cohorts overlapped in two studies, so 11 were analysed (eight prospective, for outcomes) with 67,127 participants (range 550 to 25,626). In the prospective studies, follow-up ranged from three to 30 years. Study quality was judged to be good, with scores ranging from 5 to 8 out of 9.

Overweight metabolically healthy: Without metabolic syndrome, overweight people had a similar risk of death or cardiovascular events to people of normal weight (RR 1.10 95% CI 0.90 to 1.24; seven studies; Ι²=0). In studies with at least 10 years of follow-up, overweight people were at a higher risk, but the results were not statistically significant (RR 1.21 95% CI 0.91 to 1.61; three studies; Ι²=70%).

Obese metabolically healthy: Without metabolic syndrome, obese people had a similar risk of events to people of normal weight (RR 1.19 95% CI 0.98 to 1.38; eight studies; Ι²=15%). In studies with at least 10 years of follow-up, overweight people were at a higher risk (RR 1.24 95% CI 1.02 to 1.55; four studies; Ι²=34%).

Metabolically unhealthy: For people of normal weight, those with metabolic syndrome, compared with those without it, were at a higher risk of events (RR 3.14 95% CI 2.36 to 3.93; eight studies; Ι²=97%). For overweight people, those with the syndrome were at a higher risk than people of normal weight without it (RR 2.70 95% CI 2.08 to 3.30; seven studies; Ι²=96%). For obese people, those with the syndrome were at a higher risk than people of normal weight without it (RR 2.65 95% CI 2.18 to 3.12; eight studies; Ι²=95%). Various sensitivity analyses were reported to address the heterogeneity in these results. These analyses reduced heterogeneity substantially only for overweight people.

There was no evidence of publication bias.

Authors' conclusions

Metabolically healthy obese people were at an increased risk of cardiovascular events and death from any cause, in the long term (over 10 years), compared with metabolically healthy people of normal weight. The presence of metabolic syndrome increased the risk, compared with people of normal weight without it, regardless of weight.

CRD commentary

This was generally a well-conducted review. It addressed an important public health issue, with relevant inclusion criteria. A suitable search was conducted without language restrictions, including a search of conference abstracts. Study selection and data extraction were performed by two people, reducing the risks of reviewer error and bias. Study quality was assessed and judged to be good, but all the included studies were observational, with a risk of bias, particularly confounding from unidentified factors.

A suitable meta-analysis was performed to synthesise the study results. The estimates were not adjusted for confounding factors, which increased the risk of bias due to confounding. There was considerable variation in some analyses and this could not be explained. Many of the analyses of metabolically healthy participants produced results that were not statistically significant, but the authors based their primary conclusion on one long-term subgroup analysis (four studies) that had significant results.

For these reasons, the results may be reliable, with some risk of bias, but the authors’ main conclusion appears to be too strong, given the evidence available.

Implications of the review for practice and research

Practice: The authors recommended that when predicting morbidity and mortality both obesity and metabolic health should be considered. They noted that their results might not apply to older patients or those in acute settings.

Research: The authors suggested that future studies should have a reference group of people who are both of normal weight and metabolically healthy.

Funding

Funded by the Leadership Sinai Centre for Diabetes, Canada.

Bibliographic details

Kramer CK, Zinman B, Retnakaran R. Are metabolically healthy overweight and obesity benign conditions? A systematic review and meta analysis Annals of Internal Medicine 2013; 159(11): 758-769. [PubMed: 24297192]

Indexing Status

Subject indexing assigned by CRD

MeSH

Obesity; Overweight; Humans

AccessionNumber

12013069338

Database entry date

05/12/2013

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK174043

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