Surfactant Protein D, a Marker of Lung Innate Immunity, Is Positively Associated With Insulin Sensitivity

• Published in: Diabetes care Vol. 33; no. 4; pp. 847 - 853
• Main Authors: Fernández-Real, José Manuel, Valdés, Sergio, Manco, Melania, Chico, Berta, Botas, Patricia, Campo, Arantza, Casamitjana, Roser, Delgado, Elías, Salvador, Javier, Fruhbeck, Gema, Mingrone, Geltrude, Ricart, Wifredo
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.04.2010
• Subjects: analysis; Biomarkers; Biomarkers - blood; blood; blood glucose; Blood Glucose - analysis; blood lipids; blood serum; carbon dioxide; circadian rhythm; correlation; Corticosteroids; cortisol; Cross-Sectional Studies; Dextrose; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - blood; Disease; fasting; Glucose; glucose tolerance; Humans; Immunity, Innate; Immunity, Innate - immunology; immunology; Infections; inflammation; innate immunity; Insulin; Insulin resistance; Insulin Resistance - physiology; longitudinal studies; Lung diseases; lung function; Metabolic disorders; noninsulin-dependent diabetes mellitus; obesity; Obesity - blood; Original Research; patients; physiology; Plasma; Proteins; Pulmonary Surfactant-Associated Protein D; Pulmonary Surfactant-Associated Protein D - blood; Risk factors; Studies; Surface active agents; Type 2 diabetes; Weight loss; Spain
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc09-0542

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 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.