Abstract
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 8.8 years; 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 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).ConclusionsReduced albumin is associated with an unfavorable metabolic profile, characterized by increased adipose tissue inflammation, adiposity, and glucose, and with an increased risk for T2D.
Highlights
In a larger group from this population, we evaluated the associations between albumin with body composition, glucose and insulin concentrations from the oral glucose tolerance test (OGTT), and reference measures of insulin action and secretion [insulin-stimulated glucose disposal (M) by the hyperinsulinemic-euglycemic clamp (HIEC) and acute insulin response (AIR) by the intravenous glucose tolerance test (IVGTT), respectively]
Subcutaneous adipose tissue analysis In the group that underwent adipose tissue biopsies, plasma albumin was associated with %fat (r = − 0.41, p = 0.003 l, adjusted for age and sex, Fig. 1a)
Plasma albumin was inversely correlated with gene expression markers of adipose tissue macrophage content, CSF1R (r = − 0.30, p = 0.03) and CD11b (r = − 0.36, p = 0.01), adjusted for age, sex, and %fat (Fig. 1b, c, respectively)
Summary
A strong risk factor for type 2 diabetes (T2D), is associated with adipose tissue inflammation. There is evidence for inflammation as a risk factor for development of T2D in American Indians from a community in the southwestern United States, a group which has a high incidence of T2D and obesity [6, 7]. In this population, adipose tissue markers of macrophage activation were associated with insulin action [8], and elevated peripheral leukocyte count predicted worsening insulin action and the development of T2D [9]. It is unclear whether circulating albumin is associated with either macrophage content or activation within adipose tissue
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