The origin of circulating CD36 in type 2 diabetes

OBJECTIVE: Elevated plasma levels of the fatty acid transporter, CD36, have been shown to constitute a novel biomarker for type 2 diabetes mellitus (T2DM). We recently reported such circulating CD36 to be entirely associated with cellular microparticles (MPs) and aim here to determine the absolute levels and cellular origin(s) of these CD36+MPs in persons with T2DM. DESIGN: An ex vivo case-control study was conducted using plasma samples from 33 obese individuals with T2DM (body mass index (BMI) = 39.9 +/- 6.4 kgm(-2); age = 57 +/- 9 years; 18 male: 15 female) and age-and gender-matched lean and obese non-T2DM controls (BMI = 23.6 +/- 1.8 kgm(-2) and 33.5 +/- 5.9 kgm(-2), respectively). Flow cytometry was used to analyse surface expression of CD36 together with tissue-specific markers: CD41, CD235a, CD14, CD105 and phosphatidyl serine on plasma MPs. An enzyme-linked immunosorbent assay was used to quantify absolute CD36 protein concentrations. RESULTS: CD36+MP levels were significantly higher in obese people with T2DM (P<0.00001) and were primarily derived from erythrocytes (CD235a+ = 35.8 +/- 14.6%); although this did not correlate with haemoglobin A(1c). By contrast, the main source of CD36+MPs in non-T2DM individuals was endothelial cells (CD105+ = 40.9 +/- 8.3% and 33.9 +/- 8.3% for lean and obese controls, respectively). Across the entire cohort, plasma CD36 protein concentration varied from undetectable to 22.9 mu gml(-1) and was positively correlated with CD36+MPs measured by flow cytometry (P = 0.0006) but only weakly associated with the distribution of controls and T2DM (P=0.021). Multivariate analysis confirmed that plasma CD36+MP levels were a much better biomarker for diabetes than CD36 protein concentration (P = 0.009 vs P = 0.398, respectively). CONCLUSIONS: Both the levels and cellular profile of CD36+MPs differ in T2DM compared with controls, suggesting that these specific vesicles could represent distinct biological vectors contributing to the pathology of the disease.