Air Pollution Linked With Higher Risk of Severe Hypoglycemia, Hypoglycemic Coma Among Pediatric T1D Patients

Air pollution was associated with higher glycated hemoglobin (A1C) levels and an increased risk of severe hypoglycemia in individuals with type 1 diabetes (T1D), thus leading to a higher risk of diabetes complications, according to study results published in Environmental Research.

Despite the well-established association seen between air pollution and cardio-respiratory health, evidence on the association between air pollution and diabetes is primarily based on patients with type 2 diabetes (T2D), researchers explained.

To better investigate the impact of annual averages of particulate matter with an aerodynamic diameter less than 10 mcm (PM₁₀) and PM_2.5 on A1C, daily insulin dose (IU/kg), and event rates of severe hypoglycemia among children and adolescents with T1D, authors assessed data amassed by the diabetes prospective follow-up registry (DPV) between 2009 and 2018.

The German Federal Environmental Agency provided PM₁₀ and PM_2.5 background measures. A total of 377 German centers participating in the DPV also provided data for the current analyses. All participants had T1D, were under the age of 21 when initially registered, and provided demographic and clinical data as part of the study.

Participants also had to have aggravated data of at least 2 documented treatment years, and those under the age of 1 at diabetes onset were excluded. “According to the guidelines of the International Society of Pediatric and Adolescent Diabetes (ISPAD), we defined severe hypoglycemia as an event associated with severe cognitive impairment requiring help from a third person, including seizure, convulsion or loss of consciousness (severe hypoglycemic coma),” the authors wrote.

In addition, “repeated measures linear and negative binomial regression were used to study the association between PM-quartiles (Q1 lowest, Q4 highest concentration).” A total of 44,383 participants with T1D were included in final analyses.

Analyses revealed:

• Adjusted mean A1C increased with PM₁₀ (Q1: 7.96% [95% CI, 7.95-7.98]; Q4: 8.03% [95% CI, 8.02-8.05]; P<.001) and with PM_2.5 (Q1: 7.97% [95% CI, 7.95-7.99]; Q4: 8.02% [95% CI, 8.01-8.04]; P <.001).
• Changes in daily insulin dose were inversely related to PM (PM₁₀ and PM_2.5: Q1: 0.85 IU/kg [95% CI, 0.84-0.85]; Q4: 0.83 IU/kg [95% CI, 0.82-0.83]; P <.001).
• Adjusted rates of severe hypoglycemia increased with PM-quartile groups (PM₁₀ Q1: 11.2 events/100 PY [95% CI, 10.9-11.5]; PM₁₀ Q4: 15.3 [95% CI, 14.9-15.7]; P <.001; PM_2.5 Q1: 9.9 events/100 PY [95% CI, 9.6-10.2]; PM_2.5 Q4: 14.2 [95% CI, 13.9-14.6]; P <.001).
• Higher A1C and event rates of severe hypoglycemic and hypoglycemic coma with the highest compared with the lowest particulate matter quartile were found in all age groups.

Although findings indicate an impact of annual PM₁₀ and PM_2.5 concentration on event rate of severe hypoglycemia with or without coma, researchers noted findings did not show a higher insulin requirement in children and adolescents with T1D in association with higher PM concentration.

“A plausible biological mechanism for the observed health effects in association with air pollution is oxidative stress which further leads to systemic inflammation and subsequent changes in metabolism through endothelial dysfunction, dyslipidemia, insulin resistance and impaired insulin secretion,” authors hypothesized. Previous studies have found an association between air pollution and inflammatory markers, resulting in both short- and long-term effects.

As the DPV registry represents over 85% of children with T1D in Germany, results are generalizable for T1D care in Germany. However, no assessment of personal exposure for each residential address was conducted in the current study, leaving open the possibility for misclassification. A lack of individual socioeconomic factors including education level or income may have led to residual confounding, marking an additional limitation to the study.

“Event rates of severe hypoglycemia and hypoglycemic coma increased strongly with PM₁₀-and PM_2.5-concentration,” the authors concluded. “Further studies are needed to explore causal pathways of the observed associations.”

Reference

Lanzinger S, Altug H, Schikowski T, et al. Longitudinal relationship of particulate matter and metabolic control and severe hypoglycaemia in children and adolescents with type 1 diabetes. Environ Res. Published online August 10, 2021. doi:10.1016/j.envres.2021.111859