Circulating Surfactant Protein A (SP-A), a Marker of Lung Injury, Is Associated With Insulin Resistance

Abstract

OBJECTIVES—Impaired lung function and inflammation have both attracted interest as potentially novel risk factors for glucose intolerance, insulin resistance, and type 2 diabetes. We hypothesized that circulating levels of surfactant protein (SP)-A, which reflects interstitial lung injury, could be associated with altered glucose tolerance and insulin resistance. RESEARCH DESIGN AND METHODS—Circulating SP-A concentration and metabolic variables (including insulin sensitivity by minimal model method, n = 89) were measured in 164 nonsmoking men. RESULTS—Circulating SP-A concentration was significantly higher among patients with glucose intolerance and type 2 diabetes than in subjects with normal glucose tolerance, even after adjustment for BMI, age, and smoking status (ex/never). The most significant differences were found in overweight and obese subjects with altered glucose tolerance (n = 59) who showed significantly increased serum SP-A concentrations (by a mean of 24%) compared with obese subjects with normal glucose tolerance (n = 58) (log SP-A 1.54 ± 0.13 vs. 1.44 ± 0.13; P < 0.0001). Insulin sensitivity (P = 0.003) contributed independently to 22% of SP-A variance among all subjects. In subjects with altered glucose tolerance, insulin sensitivity (P = 0.01) and fasting triglycerides (P = 0.02) contributed to 37% of SP-A variance. Controlling for serum creatinine or C-reactive protein in these models did not significantly change the results. CONCLUSIONS—Lung-derived SP-A protein was associated with altered glucose tolerance and insulin resistance in 164 nonsmoking men.