Sex differences in the link between blood cobalt concentrations and insulin resistance in adults without diabetes

Background Little is known about the effects of environmental cobalt exposure on insulin resistance (IR) in the general adult population. We investigated the association between cobalt concentration and IR. Methods A total of 1281 subjects aged more than 20 years with complete blood cobalt data were identified from the National Health and Nutrition Examination Survey (NHANES) 2015–2016 cycle. Blood cobalt levels were analyzed for their association with IR among all populations and subgroups by sex. Regression coefficients and 95% confidence intervals (CIs) of blood cobalt concentrations in association with fasting glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) were estimated using multivariate linear regression after adjusting for age, sex, ethnicity, alcohol consumption, body mass index, education level, and household income. A multivariate generalized linear regression analysis was further carried out to explore the association between cobalt exposure and IR. Results A negative association between blood cobalt concentration (coefficient = − 0.125, 95% CI − 0.234, − 0.015; P = 0.026) and HOMA-IR in female adults in the age- and sex-adjusted model was observed. However, no associations with HOMA-IR, fasting glucose, or insulin were found in the overall population. In the generalized linear models, participants with the lowest cobalt levels had a 2.74% (95% CI 0.04%, 5.50%) increase in HOMA-IR (P for trend = 0.031) compared with subjects with the highest cobalt levels. Restricted cubic spline regression suggested that a non-linear relationship may exist between blood cobalt and HOMA-IR. Conclusions These results provide epidemiological evidence that low levels of blood cobalt are negatively associated with HOMA-IR in female adults.

Cobalt Exposure in Relation to Cardiovascular Disease in the United States General Population

Cobalt exposure has adverse health effects on the cardiovascular system in occupational and laboratory studies, but these effects have not been assessed in the general population. We aimed to determine whether serum cobalt levels had relationship with the prevalence of cardiovascular disease (CVD) in the general population. Using data from the National Health and Nutrition Examination Survey (NHANES) (2015–2016), we performed the cross-sectional study. We analyzed the baseline chrematistics of 3,389 participants (1623 men and 1766 women). Generalized linear models and restricted cubic spline plots curve were undertaken to elucidate the relationship. Stratified subgroup analysis was tested to exclude interaction between different variates and cobalt. Our results showed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the quartiles of cobalt were 0.94 (0.68, 1.30), 1.58 (1.17, 2.13), and 1.84 (1.37, 2.48) compared with lowest quartile. The restricted cubic spline curve also suggested nonlinear and positive association between cobalt and CVD (P for nonlinearity = 0.005). In summary, our cross-sectional results verify that higher cobalt levels are associated with a higher prevalence of cardiovascular disease.

Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice

Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. BALB/c mice received epicutaneous applications (25 μL/ear) with 5% CoCl2*6H2O (Co) or the vehicle (Veh) dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal challenges with 0.05% CoCl2*6H2O or saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh, Veh/Co, and Co/Co. To detect early respiratory responses noninvasively, we performed sequential in vivo microcomputed tomography (µCT). One day after the last challenge, we assessed airway hyperreactivity (AHR) to methacholine, inflammation in bronchoalveolar lavage (BAL), innate lymphoid cells (ILCs) and dendritic cells (DCs) in the lungs, and serum IgE. Compared with the Veh/Veh group, the Co/Co group showed increased µCT-derived lung response, increased AHR to methacholine, mixed neutrophilic and eosinophilic inflammation, elevated monocyte chemoattractant protein-1 (MCP-1), and elevated keratinocyte chemoattractant (KC) in BAL. Flow cytometry in the Co/Co group demonstrated increased DC, type 1 and type 2 conventional DC (cDC1/cDC2), monocyte-derived DC, increased ILC group 2, and natural cytotoxicity receptor-ILC group 3. The Veh/Co group showed only increased AHR to methacholine and elevated MCP-1 in BAL, whereas the Co/Veh group showed increased cDC1 and ILC2 in lung. We conclude that dermal sensitization to cobalt may increase the susceptibility of the lungs to inhaling cobalt. Mechanistically, this enhanced susceptibility involves changes in pulmonary DCs and ILCs.