Are Metabolically Healthy Overweight and Obesity Benign Conditions?: A Systematic Review and Meta-analysis

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).

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

Studies were identified from electronic databases.

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.

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

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).

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

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.

Intramural funds from the Leadership Sinai Centre for Diabetes.