Abstract

Objective: Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.

Research Design and Methods: Serum SP-D was evaluated in 4 different cohorts. The cross sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in 2 cohorts; the cross sectional relationship with lung function in 1 cohort; and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in 1 prospective cohort.

Results: In the cross sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (p=0.005), and was negatively associated with fasting and post-load serum glucose. SP-D was also associated with HbA_1c, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than non-smokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r=0.54, p=0.034). In the longitudinal study, fasting serum SPD concentration decreased significantly after weight loss (p=0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss.

Conclusions: These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity and insulin resistance.