Surfactant protein d, a marker of lung innate immunity, is positively associated with insulin sensitivity.
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.


METHODS
Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one 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 postload serum glucose. SP-D was also associated with A1C, 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 nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D 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.
Fernández-Real
José Manuel
JM
Department of Diabetes, Endocrinology, and Nutrition, Institut d'Investigació Biomèdica deGirona, Girona, Spain. jmfernandezreal.girona.ics@gencat.cat
Valdés
Sergio
S
Manco
Melania
M
Chico
Berta
B
Botas
Patricia
P
Campo
Arantza
A
Casamitjana
Roser
R
Delgado
Elías
E
Salvador
Javier
J
Fruhbeck
Gema
G
Mingrone
Geltrude
G
Ricart
Wifredo
W
D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007328:Insulin; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000097:blood; D037663:Pulmonary Surfactant-Associated Protein D / Q000097:blood*
D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D037663:Pulmonary Surfactant-Associated Protein D