Associations between body mass index and all‐cause mortality: A systematic review and meta‐analysis

Abstract

SummaryFasting insulin and c‐reactive protein confound the association between mortality and body mass index. An increase in fat mass may mediate the associations between hyperinsulinemia, hyperinflammation, and mortality. The objective of this study was to describe the “average” associations between body mass index and the risk of mortality and to explore how adjusting for fasting insulin and markers of inflammation might modify the association of BMI with mortality. MEDLINE and EMBASE were searched for studies published in 2020. Studies with adult participants where BMI and vital status was assessed were included. BMI was required to be categorized into groups or parametrized as non‐first order polynomials or splines. All‐cause mortality was regressed against mean BMI squared within seven broad clinical populations. Study was modeled as a random intercept. β coefficients and 95% confidence intervals are reported along with estimates of mortality risk by BMIs of 20, 30, and 40 kg/m2. Bubble plots with regression lines are drawn, showing the associations between mortality and BMI. Splines results were summarized. There were 154 included studies with 6,685,979 participants. Only five (3.2%) studies adjusted for a marker of inflammation, and no studies adjusted for fasting insulin. There were significant associations between higher BMIs and lower mortality risk in cardiovascular (unadjusted β −0.829 [95% CI −1.313, −0.345] and adjusted β −0.746 [95% CI −1.471, −0.021]), Covid‐19 (unadjusted β −0.333 [95% CI −0.650, −0.015]), critically ill (adjusted β −0.550 [95% CI −1.091, −0.010]), and surgical (unadjusted β −0.415 [95% CI −0.824, −0.006]) populations. The associations for general, cancer, and non‐communicable disease populations were not significant. Heterogeneity was very large (I2 ≥ 97%). The role of obesity as a driver of excess mortality should be critically re‐examined, in parallel with increased efforts to determine the harms of hyperinsulinemia and chronic inflammation.

Associations of diabetes, hypertension and obesity with COVID-19 mortality: a systematic review and meta-analysis

“… 58 When BMI was modelled as a continuous measure, conflicting reports were found such that every 5 units (kg/m 2 ) increment in BMI increased the risk of COVID-19 mortality in one study, 58 whereas a continuous BMI measure was not associated with the risk of COVID-19 mortality in another study. 59 As observed in our analysis, most original studies on obesity and the risk of COVID-19 mortality were conducted in the countries with the highest level of obesity (ie, the USA and most of the western world). 13 60 61 Our results on the pooled adjusted risk ratios for obesity (BMI≥30 kg/m 2 ) and the risk of COVID-19 mortality are consistent with the summary RR in published meta-analyses.…”

“…The association between BMI and COVID-19 mortality appeared to be inconsistent in published studies 21 53 57–59. Persons with unclassified obesity (BMI≥30 kg/m 2 ) or those with class III obesity (BMI≥40 kg/m 2 ) were at risk of COVID-19 mortality, whereas those with obesity classes I (30≤BMI<35 kg/m 2 ) or II (35≤BMI<40 kg/m 2 ) were not at risk of COVID-19 mortality, as compared with those with normal BMI (18.5≤BMI<25 kg/m 2 ) or without obesity 58.…”

“…Persons with unclassified obesity (BMI≥30 kg/m 2 ) or those with class III obesity (BMI≥40 kg/m 2 ) were at risk of COVID-19 mortality, whereas those with obesity classes I (30≤BMI<35 kg/m 2 ) or II (35≤BMI<40 kg/m 2 ) were not at risk of COVID-19 mortality, as compared with those with normal BMI (18.5≤BMI<25 kg/m 2 ) or without obesity 58. When BMI was modelled as a continuous measure, conflicting reports were found such that every 5 units (kg/m 2 ) increment in BMI increased the risk of COVID-19 mortality in one study,58 whereas a continuous BMI measure was not associated with the risk of COVID-19 mortality in another study 59. As observed in our analysis, most original studies on obesity and the risk of COVID-19 mortality were conducted in the countries with the highest level of obesity (ie, the USA and most of the western world) 13 60 61.…”

“…Third, various BMI scales used in the studies could make it difficult to compare results across studies or countries and synthesise data in meta-analyses. For example, whereas many studies used BMI≥30 kg/m 2 to define obesity (ie, overall obesity or unclassified obesity), a few studies used BMI as classified categories (ie, underweight: <18.5 kg/m 2 , normal weight: 18.5 to <25 kg/m 2 , overweight: 25 to <30 kg/m 2 , obesity class I: 30 to <35 kg/m 2 , obesity class II: 35 to <40 kg/m 2 and obesity class III: ≥40 kg/m 2 ) or a continuous scale 59. Fourth, missing data on BMI in electronic health (medical) record systems are common 67.…”

Long-term clinical outcomes of bariatric surgery in adults with severe obesity: A population-based retrospective cohort study

“…However, higher BMI and fat percentage do not correlate with excess mortality after adjustment for fasting insulin and chronic inflammation in the general population, and in fact appear paradoxically protective. 11,12 Hyperinsulinemia and chronic inflammation have also been linked to a wide range of health conditions, including cardiovascular disease, diabetes, fatty liver, sleep apnea, cancer, chronic obstructive pulmonary disorder, dementia, and autoimmune disorders. 13,14 Given the beneficial effects of bariatric surgery on hyperinsulinemia as well as inflammatory biomarkers, it is possible that these effects contribute to the clinical benefits of bariatric surgery, which in turn may extend beyond those conditions that have been studied to date.…”