Associations of Chronic Inflammation, Insulin Resistance, and Severe Obesity With Mortality, Myocardial Infarction, Cancer, and Chronic Pulmonary Disease

Abstract

Importance: Chronic inflammation and insulin resistance often accompany severe obesity, and all are associated with disease risk.

Objective: To examine how the association of severe obesity with adverse outcomes may be modified by the presence of systemic inflammation and/or insulin resistance.

Design, setting, and participants: This population-based, retrospective cohort study included all residents of Alberta, Canada, aged 18 years and older with at least 1 procedure to ascertain severe obesity and measures of C-reactive protein, fasting glucose, triglyceride, and high-density lipoprotein cholesterol levels. Participants were observed from April 2003 to March 2017, and data analysis was conducted from June 2018 to December 2018.

Exposures: Severe obesity (body mass index ≥35 or ≥40 after January 1, 2017, as indicated with a procedure-fee modifier), chronic inflammation (all measures of C-reactive protein >10 mg/L), and a surrogate measure of insulin resistance.

Main outcomes and measures: All-cause death, first acute myocardial infarction during follow-up, first cancer diagnosis during follow-up, and new chronic pulmonary disease.

Results: Among 420 636 participants, the median age was 45 years (interquartile range, 34-56 years; range, 18-97 years), 157 799 (37.5%) were male, 185 782 (44.2%) had insulin resistance, 71 987 (17.1%) had severe obesity, and 10 770 (2.6%) had inflammation. In women with chronic inflammation, the presence of severe obesity was associated with a lower mortality risk (hazard ratio [HR], 0.75; 95% CI, 0.65-0.86), but there was no difference in risk in men with inflammation (HR, 0.89; 95% CI, 0.78-1.02). In contrast, the presence of severe obesity was associated with a higher mortality risk in men without inflammation (HR, 1.20; 95% CI, 1.13-1.26), but there was no difference in risk in women without inflammation (HR, 1.00; 95% CI, 0.95-1.06). For myocardial infarction, severe obesity was associated with increased risk in both women and men without inflammation (women: HR, 1.26; 95% CI, 1.17-1.36; men: HR, 1.35; 95% CI, 1.27-1.43) but not in women and men with inflammation (women: HR, 0.85; 95% CI, 0.67-1.07; men: HR, 0.90; 95% CI, 0.71-1.14). Severe obesity was associated with increased risk in women and men, irrespective of chronic inflammation, for new chronic pulmonary disease (women with inflammation: HR, 1.34; 95% CI, 1.23-1.46; women without inflammation: HR, 1.58; 95% CI, 1.54-1.62; men with inflammation: HR, 1.41; 95% CI, 1.29-1.54; men without inflammation: HR, 1.65; 95%, CI, 1.60-1.71) and cancer (women with inflammation: HR, 1.16; 95% CI, 1.03-1.30; women without inflammation, HR, 1.32; 95% CI, 1.28-1.36; men with inflammation: HR, 1.17; 95% CI, 1.04-1.32; men without inflammation: HR, 1.33; 95% CI, 1.28-1.39). Similar to chronic inflammation, severe obesity was not always associated with higher risk in participants with insulin resistance.

Conclusions and relevance: The findings suggest that severe obesity with systemic inflammation is associated with a different prognosis than severe obesity without inflammation.

Figure 1.. Fully Adjusted Hazard Ratios (HRs) for Clinical Outcomes in Women

A-D, The outcomes are all-cause mortality (A), first acute myocardial infarction (AMI) during follow-up (B), first cancer diagnosis (ie, solid tumors [breast, cervical, colorectal, lung, or prostate cancer], lymphoma, and metastatic cancer of any origin) during follow-up (C), and new chronic pulmonary disease (eg, chronic obstructive pulmonary disease, bronchitis, pneumonoconiosis, or asthma) in those without prior chronic pulmonary disease (D). Hollow markers indicate no significant difference between participants with and without severe obesity. IR indicates insulin resistance.

Figure 2.. Fully Adjusted Hazard Ratios (HRs) for Clinical Outcomes in Men

A-D, The outcomes are all-cause mortality (A), first acute myocardial infarction (AMI) during follow-up (B), first cancer diagnosis (ie, solid tumors [breast, cervical, colorectal, lung, or prostate cancer], lymphoma, and metastatic cancer of any origin) during follow-up (C); and new chronic pulmonary disease (eg, chronic obstructive pulmonary disease, bronchitis, pneumonoconiosis, or asthma) in those without prior chronic pulmonary disease (D). Hollow markers indicate no significant difference between participants with and without severe obesity. IR indicates insulin resistance.