Reduced plasma albumin predicts type 2 diabetes and is associated with greater adipose tissue macrophage content and activation

BackgroundPlasma albumin is reduced during inflammation. Obesity, a strong risk factor for type 2 diabetes (T2D), is associated with adipose tissue inflammation. However, whether albumin is associated with adipose tissue inflammation and whether it predicts T2D are unclear.MethodsAdults (predominantly American Indian) from a longitudinal study were included. Macrophage content and gene expression related to recruitment/activation were measured from subcutaneous adipose tissue (n=51). The relationship between plasma albumin and adiposity (dual-energy X-ray absorptiometry or hydrodensitometry), glucose (oral glucose tolerance test), insulin action (hyperinsulinemic-euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were evaluated (n=422). Progression to T2D was evaluated by Cox regression (median follow-up 8.8years; 102 progressors).ResultsAlbumin was associated with macrophage markers including C1QB (r=-0.30, p=0.04), CSF1R (r=-0.30, p=0.03), and CD11b (r=-0.36, p=0.01). Albumin was inversely associated with body fat percentage (r=-0.14, p=0.003), fasting plasma glucose (r=-0.17, p=0.0003), and 2h plasma glucose (r=-0.11, p=0.03), and was reduced in impaired glucose regulation compared with normal glucose regulation (meanSD: 39.4 +/- 3.6g/l and 40.1 +/- 3.9g/l, respectively; p=0.049). Albumin predicted T2D, even after adjustment for confounders (HR, 0.75; 95% CI 0.58-0.96; p=0.02; per one SD difference in albumin).Conclusions Reduced albumin is associated with an unfavorable metabolic profile, characterized by increased adipose tissue inflammation, adiposity, and glucose, and with an increased risk for T2D.