Ambient Air Pollution and Type 2 Diabetes: Do the Metabolic Effects of Air Pollution Start Early in Life?

The adverse health effects of ambient (outdoor) air pollution have been recognized since increased mortality due to smog was reported in London in 1952 (1). Suspended particles (particulate matters) from soot were associated with increased mortality and morbidity related to both respiratory and cardiovascular disorders (1). Since then, great efforts have been made to control ambient air pollution on a national level. For example, the Clean Air Act in the U.S. resulted in improvements in ambient air quality. Between 1990 and 2015, annual concentrations of particulate matter ,10 mm in aerodynamic diameter (PM10) dropped by 39% in the U.S. (2). Nonetheless, ambient air pollution is still one of the leading causes of global disease burden (3,4). In fact, the World Health Organization has estimated that ambient air pollution is responsible for more than 3 million deaths, representing 5.4% of total deaths in 2012 (5). Recently, scientific communities have suggested that ambient air pollution may increase the risk of type 2 diabetes. Animal models have provided convincing evidence and suggested potential mechanisms including particle-mediated alterations in glucose homeostasis, inflammation in visceral adipose tissue, endoplasmic reticulum stress in liver and lung, mitochondrial dysfunction and brown adipose tissue dysfunction, inflammation mediated through Toll-like receptors and nucleotide-binding oligomerization domain-like receptors, and inflammatory signaling in key regions of the hypothalamus (6). Although the evidence is still limited, epidemiological studies have also supported the hypothesis that ambient air pollution exposure is associated with elevated risk for type 2 diabetes (7–9). Important questions not fully addressed by the literature include the following: 1) what are the potential mechanisms supported by human population data? and 2) when do the adverse metabolic effects of ambient air pollution start? In this issue of Diabetes, Alderete et al. (10) address these questions by evaluating the associations between longterm ambient air pollution exposure and longitudinal measures of insulin resistance, b-cell functions, and adiposity in 314 overweight and obese Latino children aged 8 to 15 years at baseline in Los Angeles, California. This study evaluated two air pollutants: nitrogen dioxide (NO2), a measure of traffic-related exposure, and PM2.5, an indicator of both traffic-related and regionally transported particles. Longterm exposure to these air pollutants were computed as yearly concentrations averaged over an individual’s followup. This study is unique in that direct measures of glucose homeostasis based on the frequently sampled intravenous glucose tolerance test were used rather than indirect estimates from fasting glucose and insulin (i.e., HOMA of insulin resistance). In addition, the measures were longitudinally assessed for an average of 3.4 years with an average of four repeated measurements, allowing the investigators to evaluate whether higher exposure to ambient air pollution accelerates impairments in insulin sensitivity and b-cell function. The authors report that higher exposure to both NO2 and PM2.5 were statistically significantly associated with a faster decline in the whole-body insulin sensitivity measure. NO2, but not PM2.5, was statistically significantly associated with a faster decline in the disposition index, an indicator of b-cell function. These associations were observed after adjustment for important confounding factors such as social position and body fat percent, suggesting that the observed associations are independent of socioeconomic status and adiposity, although residual confounding by built environment and residential noise could not be ruled out (11,12). In addition, both NO2 and PM2.5 were statistically significantly associated with faster increases in BMI and subcutaneous abdominal adipose tissue. This study failed to show that either NO2 or PM2.5 was statistically significantly associated with visceral fat increments, a potential mechanism supported by animal studies (13,14). Traditionally,