Impaired postprandial adipose tissue microvascular blood flow responses to a mixed-nutrient meal in first-degree relatives of adults with type 2 diabetes

Adipose tissue microvascular blood flow (MBF) is stimulated postprandially to augment delivery of nutrients and hormones to adipocytes. Adipose tissue MBF is impaired in type 2 diabetes (T2D). Whether healthy individuals at-risk of T2D show similar impairments is unknown. We aimed to determine whether adipose tissue MBF is impaired in apparently healthy individuals with a family history of T2D. Overnight-fasted individuals with no family history of T2D for two generations (FH-, n=13), with at least one parent with T2D (FH+, n=14) and clinically diagnosed T2D (n=11) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin, plasma non-esterified fatty acids [NEFA] and fat oxidation) were measured before and during the MMC. MBF in truncal subcutaneous adipose tissue was assessed by contrast ultrasound while fasting and 60 minutes post-MMC. FH+ had normal blood glucoses, increased adiposity, impaired post-MMC adipose tissue MBF (D0.70±0.22 versus 2.45±0.60 AI/sec, p=0.003) and post-MMC adipose tissue insulin resistance (Adipo-IR index; D45.5±13.9 versus 7.8±5.1 mmol/L x pmol/L, p=0.006) compared to FH-. FH+ and T2D had an impaired ability to suppress fat oxidation post-MMC. Fat oxidation incremental area under the curve (35-55 minutes post-MMC, iAUC) was higher in FH+ and T2D, compared to FH- (p=0.002 and 0.004, respectively). Postprandial MBF was negatively associated with postprandial fat oxidation iAUC (p=0.01). We conclude that apparently healthy FH+ individuals display blunted postprandial adipose tissue MBF that occurs in parallel with adipose tissue insulin resistance and impaired suppression of fat oxidation, which may help explain their heightened risk for developing T2D.