Associations of long-term exposure to air pollution with glucose homeostasis biomarkers and diabetes-related comorbidities in people with recent-onset type 1 and type 2 diabetes

Aims/hypothesis Air pollution (AP) contributes to diabetes progression and comorbidities, but underlying mechanisms remain unclear, as no observational studies have applied gold-standard phenotyping or distinguished between the effects of type 1 diabetes, type 2 diabetes and diabetes subtypes. We examined whether AP exposure was associated with glucose homeostasis biomarkers and diabetes-related comorbidities in people with recent-onset type 1 diabetes, type 2 diabetes and diabetes subtypes. Methods This cross-sectional analysis is based on data from 1120 participants in the German Diabetes Study (417 with type 1 diabetes and 703 with type 2 diabetes). The glucose homeostasis biomarkers used were HbA 1c , insulin sensitivity (clamp-derived M value), insulin secretion (glucagon-stimulated C-peptide 6min ) and insulin clearance (clamp derived). Diabetes-related comorbidities included CVD risk (SCORE2-Diabetes), V̇O₂ₘₐₓ V ˙ O 2 max as an indicator of cardiorespiratory fitness, albuminuria as a marker of kidney function and the presence of distal sensorimotor polyneuropathy (DSPN). Five-year means of exposure to AP (particulate matter [PM] with diameters of <2.5 μm [PM 2.5 ] and <10 μm [PM 10 ] and nitrogen dioxide [NO 2 ] before baseline at individual residential addresses were examined. Associations between each exposure–outcome pair were estimated per 1 IQR increase in air pollutants using multivariable linear and logistic regression. Two-pollutant analysis, cumulative risk index (CRI) analysis and insulin-treated type 1 diabetes model analysis were performed as sensitivity analyses. Results Among those with type 1 diabetes, higher PM 2.5 was associated with higher HbA 1c (exp[β]=1.07 [95% CI 1.03, 1.11]), insulin secretion (exp[β]=1.19 [95% CI 1.03, 1.36]), lower V̇O₂ₘₐₓ V ˙ O 2 max (exp[β]=0.94 [95% CI 0.89, 0.99]) and higher albuminuria (exp[β]=1.72 [95% CI 1.34, 2.20]). Among type 2 diabetes, higher PM 2.5 was associated with higher HbA 1c (exp[β]=1.04 [95% CI 1.01, 1.06]), lower insulin sensitivity (β=−0.42 [95% CI −0.82, −0.03]), lower insulin secretion (exp[β]=0.94 [95% CI 0.89, 0.99]), lower insulin clearance (exp[β]=0.92 [95% CI 0.87, 0.98]), higher CVD risk (exp[β]=1.07 [95% CI 0.99, 1.16]), lower V̇O₂ₘₐₓ V ˙ O 2 max (exp[β]=0.91 [95% CI 0.88, 0.95]), higher albuminuria (exp[β]=1.71 [95% CI 1.41, 2.08]) and higher odds of DSPN (OR 1.53 [95% CI 1.02, 2.32]). Similar associations were observed for PM 10 and NO 2 . Associations were directionally attenuated in two-pollutant models but remained consistent in CRI and insulin-treated type 1 diabetes analyses. Differences were observed in associations between diabetes subtypes. Conclusions/interpretation Long-term AP exposure was consistently associated with higher HbA 1c ; reduced whole-body insulin sensitivity, secretion and clearance; and an increased burden of diabetes-related comorbidities in type 2 diabetes. Associations were less consistent in type 1 diabetes. Trial registration ClinicalTrials.gov NCT01055093