Background:

Recent interest has focused on a unique subgroup of overweight and obese individuals who have normal metabolic features despite increased adiposity. Normal-weight individuals with adverse metabolic status have also been described. However, it remains unclear whether metabolic phenotype modifies the morbidity and mortality associated with higher body mass index (BMI).

Purpose:

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

Data Sources:

Studies were identified from electronic databases.

Study Selection:

Included studies evaluated all-cause mortality or cardiovascular events (or both) and clinical characteristics of 6 patient groups defined by BMI category (normal weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined by the presence or absence of components of the metabolic syndrome by Adult Treatment Panel III or International Diabetes Federation criteria.

Data Extraction:

Two independent reviewers extracted the data. Metabolically healthy people of normal weight made up the reference group.

Data Synthesis:

Eight studies (n = 61 386; 3988 events) evaluated participants for all-cause mortality and/or cardiovascular events. Metabolically healthy obese individuals (relative risk [RR], 1.24; 95% CI, 1.02 to 1.55) had increased risk for events compared with metabolically healthy normal-weight individuals when only studies with 10 or more years of follow-up were considered. All metabolically unhealthy groups had a similarly elevated risk: normal weight (RR, 3.14; CI, 2.36 to 3.93), overweight (RR, 2.70; CI, 2.08 to 3.30), and obese (RR, 2.65; CI, 2.18 to 3.12).

Limitation:

Duration of exposure to the metabolic–BMI phenotypes was not described in the studies and could partially affect the estimates.

Conclusion:

Compared with metabolically healthy normal-weight individuals, obese persons are at increased risk for adverse long-term outcomes even in the absence of metabolic abnormalities, suggesting that there is no healthy pattern of increased weight.

Primary Funding Source:

Intramural funds from the Leadership Sinai Centre for Diabetes.