Impairments in adipose tissue microcirculation in type 2 diabetes mellitus assessed by real-time contrast-enhanced ultrasound

BACKGROUND: In obesity and type 2 diabetes mellitus (T2D),adipose tissue expansion (because of larger adipocytes) results in reduced microvascular density which is thought to lead to adipocyte hypoxia, inflammation,and reduced nutrient delivery to the adipocyte. Adipose tissue microvascular responses in humans with T2D have not been extensively characterized.Furthermore, it has not been determined whether impaired microvascular responses in human adipose tissue are most closely associated with adiposity, inflammation, or altered metabolism. METHODS AND RESULTS:Overnight-fasted healthy controls(n=24,9 females/15 males) and people with T2D (n=21,8 females/13 males) underwent a body composition scan (dual-energy X-ray absorptiometry),an oral glucose challenge (50 g glucose) and blood analysis of clinical chemistries and inflammatory markers.Abdominal subcutaneous adipose tissue microvascular responses were measured by contrast-enhanced ultrasound at baseline and 1-hour post-oral glucose challenge. Adipose tissue microvascular blood volume was significantly elevated in healthy subjects 1-hour post-oral glucose challenge; however, this effect was absent in T2D. Adipose tissue microvascular blood flow was lower in people with T2D at baseline and was significantly blunted post-oral glucose challenge compared with controls. Adipose tissue microvascular blood flow was negatively associated with truncal fat(%),glucoregulatory function,fasting triglyceride and nonesterified fatty acid levels, and positively associated with insulin sensitivity. Truncal fat (%),systolic blood pressure, and insulin sensitivity were the only correlates with microvascular blood volume.Systemic inflammation was not associated with adipose tissue microvascular responses.CONCLUSIONS: Impaired microvascular function in adipose tissue during T2D is not conditionally linked to systemic inflammation but is associated with other characteristics of the metabolic syndrome (obesity, insulin resistance, hyperglycemia, and dyslipidemia).