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

Background: Plasma 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.

Methods: Adults (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 8.8 years; 102 progressors).

Results: Albumin 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 2 h plasma glucose (r = - 0.11, p = 0.03), and was reduced in impaired glucose regulation compared with normal glucose regulation (mean ± SD: 39.4 ± 3.6 g/l and 40.1 ± 3.9 g/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.