Abstract Rationale Metabolic dysfunction and insulin resistance have been increasingly implicated in asthma, but there has been limited investigation in chronic obstructive pulmonary disease (COPD). Furthermore, prior studies often rely on single glycemic biomarkers rather than a multidimensional assessment of glucose homeostasis. Fructosamine reflects glycemic control over 2-3 weeks. We hypothesized that type 2 diabetes status and circulating glucose and fructosamine levels would be associated with adverse pulmonary outcomes in the SPIROMICS cohort. Methods We assessed the relationship between self-reported diabetes and outcomes among all 2,976 SPIROMICS participants (current/former smokers with and without airflow obstruction) and analyzed fasting plasma glucose in 1,054 and fructosamine in 1,162 participants from baseline serum samples. Associations of diabetes and each biomarker with mutual adjustment for diabetes with FEV1% and FVC% predicted, respiratory symptoms (dichotomized CAT 10 or 10), quality of life (assessed by SGRQ) and six-minute walk distance (6MWD), and baseline retrospective exacerbation rates were assessed using multivariable linear and negative binomial regression, adjusting for age, sex, race, BMI, smoking status, and pack-years. Results Of the 2,976 participants, 392 had self-reported diabetes status. Mean age was 64, 47% were female, and mean FEV1% was 79%. Of those with glucose and fructosamine measurements, 157 were diabetic. The 157 individuals with diabetes had higher glucose (111 mg/dL versus 85 mg/dL, p 0.001) and fructosamine (706 umol/L versus 617 umol/L, p 0.001) than the 939 non-diabetics. Diabetes status was associated with worse baseline FEV1% predicted (-2.73; -5.31, -0.16), worse CAT (1.81; 1.41, 2.35) and SGRQ scores (5.66; 3.38, 7.94), and lower 6MWD (-26.10; -38.81, -13.39), after multivariable adjustment. Self-reported diabetes was associated with retrospective severe exacerbation, but not retrospective moderate exacerbation. However, neither glucose nor fructosamine were associated with study outcomes after multivariable adjustment. Sensitivity analyses assessing these measures among patients without diabetes yielded similar neutral results. Conclusions In SPIROMICS, self-reported diabetes but not glucose or fructosamine were associated with lung function, respiratory symptoms, walk distance, and severe exacerbations. These findings suggest that factors associated with diabetes, beyond hyperglycemia itself, may influence airway disease progression. It may also be a single time cross-sectional measurement is inadequate to capture risk from glycemic dysfunction or that fructosamine may be less reliable in the setting of chronic illness. Future studies should measure glucose and fructosamine in larger sample sizes and incorporate measurement of other diabetes-related factors such as insulin resistance to better elucidate pathomechanisms between metabolic dysregulation and poor COPD outcomes. This abstract is funded by: NIH NHLBI K23HL173570
Tejwani et al. (Fri,) studied this question.