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Association of Ambient Air Pollution Exposure with Glycated Hemoglobin (HbA1c) Levels

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dr. Karunia Valeriani Japar

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Introduction

Exposure to ambient air pollution has emerged as a significant contributor to global morbidity and mortality, particularly through its effects on cardiometabolic health. Fine particulate matter (PM2.5) and nitrogen dioxide (NO2), two key urban pollutants generated mainly by traffic, industry, and biomass combustion, have been increasingly implicated in the pathogenesis of metabolic disorders. Recent epidemiologic studies reveal that chronic exposure to PM2.5 and NO2 is associated not only with an elevated risk of type 2 diabetes, but also with higher levels of glycated hemoglobin (HbA1c), a biomarker of long-term glycemic control and diabetes complication risk [1,2,3,4].

Mounting evidence suggest that air pollution may influence glucose metabolism through mechanisms involving systemic inflammation, oxidative stress, and endothelial dysfunction, even in populations without pre-existing metabolic disease. The clinical and public health implications are profound, as modest increases in HbA1c due to ambient pollution may contribute to growing burden of diabetes and its complications, particularly in densely populated and socioeconomically disadvantaged areas [1,2,3,4,5].

This article reviews current evidence linking PM2.5 and NO2 exposure with increased HbA1c levels, highlights key mechanistic pathways, and discusses the implications for urban populations and metabolic health risk stratification [1,2,4,5].

What is Air Pollution and It’s Component

Air pollution is defined as the introduction of harmful substances into the Earth’s atmosphere, resulting in detrimental effects on human health, ecosystems, and various manmade structures. These substances, known as air pollutants, may be present in gaseous, liquid, or solid form, and are either emitted directly from natural and anthropogenic sources or formed via complex atmospheric reactions [6,7,8,].

Particulate matter and noxious gases constitute the principal components of air pollution. Fine particulate matter with an aerodynamic diameter less than 2.5 micrometers (PM2.5) is particularly concerning due to its ability to penetrate deep into the pulmonary alveoli and enter systemic circulation. PM2.5 is generated primarily from combustion of fossil fuels, industrial activity, vehicular emissions, and biomass burning, and is characterized by a heterogenous composition including organic chemicals, metals, and secondary reaction products. Chronic exposure to PM2.5 has been closely linked to increased incidence of pulmonary, cardiovascular, and metabolic diseases [7,8].

Nitro dioxide, a reddish-brown reactive gas produced by high-temperature combustion in vehicles, power plants, and industrial operations, is a prominent urban air pollutant. NO2 serves not only as a direct respiratory irritant but also as a precursor for secondary pollutant. Such as ground-level ozone and fine particulate matter. Epidemiological research increasingly implicates NO2 exposure in the pathogenesis of respiratory, cardiovascular, and metabolic disorders [7,8,9].

PollutantMain SourcesHuman Health Impact
PM2-5Industry, traffic, biomass burnRespiratory, metabolic, systemic
NO2Vehicle emissions, power plantsRespiratory, cardiovascular, metabolic
COVehicle, firesHeart, neurological
O3Reaction of NO2 +VOCsLung, respiratory
SO2Fossil fuel combustionAsthma, haze, acid rain
PbIndustry, combustionNeurology, development
Table 1. Air Pollution Components

Mechanism of How PM2.5 Increased HbA1C

Extensive epidemiological and mechanistic evidence supports the role of PM2.5 in increasing HbA1c, an established marker of long-term glycemic control and diabetes risk [1,2,3,10,11].

Long-term exposure to ambient PM2.5 has been robustly linked to higher HbA1c levels and increased risk of type 2 diabetes (T2D) across populations. In a representative US cohort, one-year interquartile-range increases in PM2.5 were associated with 1.8% higher HbA1c among diabetic participants (p<0.01), and with a 35% higher prevalence-odds of diabetes. In China, Liu et al. found a 0.08% increment in HbA1c per 41.1m/m3 increase in PM2.5 among 11,847 adults, evidence supported by large studies in Israel (HbA1c + 2.93% per 22.3mg/m3 increase). Similar trends were observed in Taiwanese and European cohorts, confirming both the dose-response relationship and the generalizability across geographic settings [2,10,11,12,13].

Mechanistically, PM2.5 exerts its glycemic effects through several pathways: systemic inflammation, oxidative stress, endothelial dysfunction, and neurogenic disruption. PM2.5 inhalation triggers a cascade of inflammatory cytokines (TNFa, IL-1b) and oxidative injury, impairing insulin signaling and pancreatic b-cell function. Recent research implicates activation of the transient receptor potential vanilloid 1 (TRPV1) channel- a molecular hub of metabolic and neurogenic inflammation- further linking air pollution exposure with metabolic derangements. Epidemiological findings align with these mechanistic insights, reporting that intermediate-term PM2.5 exposure (3-6 months) increases HbA1c by approximately 0.28% (95% CI: 0.41-0.42%) per 1m/m3 increment. The effect is pronounced in individuals with pre-existing metabolic conditions or those residing in urban environments with dense traffic and industrial emissions [1,3,10,12,14].

Experimental animal and occupational studies bolster epidemiological data, with evidence of PM2.5-induced b-cell inflammation, insulin resistance and higher blood HbA1c among exposed workers and rodents. The effect is more pronounced with smaller particle sizes and longer duration of exposure, paralleling observations in mechanistic studies [3,10,12,13].

Figure 1. Physiologic Pathways of How Air Pollutant Can Contribute to Clinical Outcomes[1]
  • Direct Linkes to Impaired Insulin Signaling and Beta-Cell Injury
    • Systemic inflammation and oxidative stress elevate circulating cytokines, hampering insulin receptor signaling in target tissues and reducing insulin sensitivity.
    • TRPV1 channel activation by PM2.5 amplifies sympathetic overactivity, neurogenic inflammation, and impairs pancreatic beta-cell function.
    • Mitochondrial dysfunction in skeletal muscle and other tissues disrupts glucose and lipid homeostasis, directly promoting insulin resistance.
    • Endothelial dysfunction lessens capillary insulin delivery and impairs tissue glucose uptake.
MechanismMolecular Cascade SummaryResult/Impact on Metabolic Health
Systemic Inflammation­IL-1b, TNFa from immune and b-cells; chronic insulin resistanceb-cell injury, decreased insulin secretion [12,25]
TRPV1 ActivationDirect activation by PM2.5/DEPs; ­SNS, neurogenic inflammationImpaired metabolism, further inflammation [10,26]
Oxidative StressExcess ROS, mitochondrial damage, redox imbalance in tissuesEndothelial, beta-cell dysfunction [4,27]
Endothelial DysfunctionSuppressed insulin eNOS signaling; vascular damageImpaired glucose uptake, insulin resistance [4,25]
Table 2. Schematic Table: PM2.5-Induced Molecular Pathways

In summary, the relationship between ambient PM 2.5 and elevated HbA1c is consistent across large scale epidemiological cohorts, mechanistic animal models, and occupational exposure studies. This association is biologically plausible, dose-dependent, and contributes to increasing risk and prevalence of diabetes complications [1,2,3,10,11,13].

Epidemiological Evidence

Multiple large-scale epidemiological studies consistently demonstrate a strong and independent association between ambient PM2.5/NO2 exposure and elevations in HbA1C levels, fasting plasma glucose, and incident T2DM:

  • Cohort and Population-Based Studies
    • In a pooled US cohort (n= 7,089; both diabetic and non-diabetic), an interquartile range (IQR) increase in one-year mean PM2.5 (3.9mg/m^3) was associated with 1.4 ±3% higher HbA1c. while an IQR increase in NO2 (8.6ppb) resulted in 2.0% ± 0.3% increase in HbA1c [2].
    • A Chinese rural cohort (n=39,259) demonstrated per 1m/m^3 increases of PM2.5 and NO2 were associated with 6.8% and 5.0% increased odds for T2DM, and 0.036 mmol/L and 0.030 mmol/L higher fasting glucose, respectively [2,15].
    • Among diabetic patients in Israel (n= 73,117), an IQR increase in PM2.5 (22.3mg/m^3) correlated with a 2.93% increase in HbA1c (95% CI: 0.35%, 5.59%).
    • Similar positive associations were replicated in Taiwanese elderly (2.10% higher HbA1c per 20.42mg/m^3 increase in PM2.5) and urban European populations [2].
    • Meta-analyses confirm higher PM2.5 exposure corresponds with increased fasting glucose and HbA1c, even after excluding known diabetics, highlighting the population-level risks [2,16].
    • Meta-analyses confirm higher PM 2.5 exposure corresponds with increased fasting glucose and HbA1c, even after excluding known diabetics, highlighting the population-level risks [11,15,17].
  • Dose-Response and Susceptibility
    • The dose-response relationship is consistent and robust: greater duration and concentration of PM 2.5 and NO2 lead to progressively higher HbA1c levels and more diabetes incidence, with elderly, male and lower socioeconomic status populations at particularly elevated risk [2,15].
    • Associations are significant even after adjusting for cofounders and in two-pollutant models, supporting causal inference rather than mere correlation [1,2,11,15].

Mechanistic Insights

  • Inflammation and Oxidative Stress
    • 5 and NO2 exposure induces systemic inflammation characterized by elevated TNF-a, IL-6 and CRP, disrupting insulin signaling and glucose transport [1,10].
    • Oxidative damage is directly linked to endothelial dysfunction, increased insulin resistance, and impaired pancreatic b-cell activity, leading to poor glycemic control and elevated HbA1c [1,10].
  • Neuroendocrine and Molecular Mechanisms
    • Activation of neurogenic signaling pathways such as TRPV1 have been implicated as a molecular link between PM2.5 exposure and metabolic dysregulation, promoting hyperglycemia [10].
    • Preclinical studies (animals models, occupational exposures) show that inhaled PM2.5 increases circulating inflammatory cytokines, impairs b-cell activity, elevated HbA1c [10,11].
    • NO2 further amplifies systemic inflammation and promotes the generation of secondary PM via atmospheric chemistry, compounding metabolic risk.

Clinical Implications

  • Glycemic Control and Risk Stratification
    • The observed increments in HbA1c due to PM2.5/NO2 exposure, although moderate, are clinically meaningful and translate to increased risks of microvascular complications, cardiovascular events, and mortality among diabetic and non-diabetic populations [1,2,11,16].
  • Policy and Translational Health
    • Local environmental planning, green infrastructure, and policy initiatives targeting air quality improvements have both direct and indirect metabolic health benefits [18].
    • Screening for air pollution exposure should be considered in risk assessment frameworks for diabetes management and prevention.

How to Avoid Exposure of PM 2.5 and NO2

Reducing exposure PM2.5 and NO2 is essential to lower the risk of elevated HbA1c and subsequent metabolic complications. Evidence-based strategies span personal behaviors, household interventions, and community action [19,20].

  • Evidence-Based Personal Strategies
    • Monitor air quality: Use apps or websites to check local air pollution levels and avoid outdoor activities during high-pollution periods, such as rush hours or pollution episodes.
    • Use effective face masks: Certified N95 or N99 respirators can substantially lower PM2.5 inhalation compared to cloth or surgical masks, especially outdoors or in polluted environments.
    • Plan activities away from heavy traffic: Avoid exercising or walking within 400 meters of major roads or industrial sites, where PM2.5 and NO2 concentrations are highest.
  • Optimizing Indoor Air Quality
    • Air purifiers: Use indoor air purifiers equipped with HEPA filters (and check ratings for PM2.5 effectiveness); this significantly lowers indoor PM2.5.
    • Close windows during pollution peaks: Keep windows closed and use air conditioning or mechanical ventilation with high efficiency filters (MERV 7-13).
    • Regular cleaning: Dust and mop floor frequently; PM2.5 can accumulate indoors via infiltration and indoor sources.
    • Switch off indoor combustion sources: Avoid smoking indoors; opt for electric/induction cooking instead of gas, which generates NO2.
    • Properly vent gas appliances: Use exhaust fans vented outdoors over gas stoves, and service all gas heaters regularly to minimize indoor NO2 levels.
    • Create a clean air room: For high-risk individuals, consider dedicating one well-sealed, filtered room at home for sleep and rest during pollution episodes.
  • Community and Environmental Actions
    • Reduce vehicle use: Walk, cycle, use public transport, and avoid unnecessary car journeys, especially in high-traffic locations.
    • Advocate for urban greenspaces: Green infrastructure (parks, trees) improves local air quality by trapping particulates and diluting gaseous pollutants.
    • Encourage pollution control policies: Support policies for cleaner public transport, industrial emission reductions, and clean energy adoption.
StrategyEffect on PM2.5/NO2
HEPA air purifiers, closed windows¯ Indoor PM2.5 [20,21,22]
N95/N99 respirators¯ Personal PM 2.5 [20]
Electric cooking, vented heaters¯ Indoor NO2 [23,24]
Avoiding rush hour & traffic¯ Outdoor PM2.5/NO2 [19,20]
Urban greenspaces¯ Local pollution [18]
Table 3. Summary Table

Conclusion

In summary, a robust body epidemiological, mechanistic, and clinical evidence supports the association between long-term exposure to PM2.5 and NO2 and elevated HbA1c levels, both in diabetic and non-diabetic populations. Chronic exposure to these airborne pollutants, primarily derived from traffic, industrial activity, and urban combustion sources, is consistently linked to an increased risk of type 2 diabetes, worsened glycemic control, and greater burden of vascular and metabolic complications. Mechanistically, this relationship is underpinned by systemic inflammation, oxidative stress, endothelial dysfunction, and neuroendocrine disruption, each contributing to impaired insulin sensitivity and b-cell injury.

The observed increases in HbA1c associated with PM2.5 and NO2 exposure are not only statistically significant but also clinically meaningful, even after adjusting for traditional cofounders. This has major implications for urban health policies, diabetes risk stratification, and public health interventions- especially in vulnerable, densely populated, or socioeconomically disadvantaged communities. Mitigation strategies that reduce personal, household, and community-level exposure to PM2.5 and NO2 are essential to blunt the metabolic consequences of air pollution and should be integrated into diabetes prevention and management frameworks.

As urbanization trend accelerated and air quality challenges intensify, urgent interdisciplinary action is warranted to address this modifiable risk factor and limit its adverse metabolic and cardiovascular consequences.

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