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

Abstract

OBJECTIVEImpaired 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 METHODSSerum 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.RESULTSIn 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.CONCLUSIONSThese findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.

SP-D Polymorphisms and the Risk of COPD

“…As shown in Table 6, age (Beta = 0.36, p < 0.001), and steroid intake (Beta = −0.36, p < 0.001) and rs3088308 influence serum SP-D levels (Beta = −0.33, p < 0.001) along with exacerbation status (Beta = 0.28, p = 0.01), body mass index (Beta = −0.26, p = 0.01) and SNP rs721917 (Beta = −0.21, p = 0.03). Our study supports the previous studies correlating age [29], body mass index [31,32], corticosteroid intake [33] and rs721917 [29,31,39] with systemic SP-D levels. We have previously reported on significantly raised serum SP-D levels in COPD exacerbations [34].…”

Increased expression of immune-related genes in leukocytes of patients with diagnosed gestational diabetes mellitus (GDM)

“…High-quality total RNA (4 mg) was reverse-transcribed with the use of a (dT) 18 primer and RevertAid TM H Minus MMuLV reverse transcriptase (Fermentas, Lithuania), according to the manufacturer's recommendations. The levels of NOS2 and SFTPD transcripts were analyzed by quantitative real time PCR (qRT-PCR) with the use of Maxima TM SYBR Green/ROX qPCR Master Mix (2 x) (Thermo Scientific, United States) and specific primers for NOS2, SFTPD, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a housekeeping gene.…”

“…In fact, decreased serum SP-D concentration has been reported in subjects with obesity and T2DM and it negatively correlates with fasting and post-load serum glucose. 18 Additionally, SFTPD gene polymorphisms have been found to associate with insulin resistance and T2DM. 19 Although a great deal of information concerning the relationship between immune-related genes such as NOS2 and SFTPD, and diabetes including T1DM and T2DM has been gained in recent years, no progress has been made toward understanding their significance in leukocytes obtained from GDM patients.…”

“…There is growing evidence suggesting that SP-D can be an important factor at the cross-roads of inflammation, obesity, and insulin resistance. 18,34 In fact, serum SP-D concentration is reduced in subjects with both obesity and T2DM and, moreover, it inversely associates with fasting and post-load serum glucose and positively links to insulin sensitivity. 18 In the light of these findings, our study showing significantly increased leukocyte SFTPD expression in hyperglycemic GDM patients, as well as its positive correlations with fasting plasma glucose, HOMA-IR, and CRP in the entire study group is rather surprising.…”

Pathogenic Features of Insulin Resistance and Critical Organ Damage in the Liver, Muscle and Lung

“…Fernández-Real (2008) found that SP-A levels in the blood were significantly higher among patients with glucose intolerance and type 2 diabetes than in those with normal glucose tolerance, even after adjustment for BMI, age, and smoking status. Additionally, SP-D, a lung-derived innate immune protein, is also associated with inflammation and metabolic abnormalities including insulin sensitivity [Fernández-Real, 2010]. Indeed, in the obese type 2 diabetes animal model, many qualitatively similar changes as in type 1 diabetes develop with extensive lipid deposition, altered alveolar type-2 cell ultrastructure and surfactant protein expression patterns [Foster, 2010].…”