Replacing carbohydrate with protein and fat in prediabetes or type-2 diabetes: greater effect on metabolites in PBMC than plasma

BACKGROUND: Active metabolism of peripheral blood mononuclear cells (PBMC) could suggest their suitability for metabolomics studies. This study examined whether reductions in PBMCs and plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activities induced by dietary intervention affected the overall metabolic profiles of PBMC and plasma. METHODS: Eighty nonobese subjects aged 40–70 years (18.5 ≤ BMI < 30 kg/m(2)) with prediabetes or newly-diagnosed type-2 diabetes were assigned to consume either the usual refined-rice diet (control group, n = 40) or to replace refined rice with whole grains and legumes as carbohydrates (whole-grain group, n = 40) for three meals per day during the 12-week intervention. Fasting PBMC and plasma metabolomes were profiled using UPLC-LTQ-Orbitrap mass spectrometry. RESULTS: After 12 weeks, changes in fasting glucose, HbA(1c), HOMA-IR, MDA, ox-LDL, LDL particle size, plasma Lp-PLA(2) activity, and PBMC enzyme activity in the whole-grain group were significantly different from those in the control group before and after adjusting for baseline levels. The PBMC levels of L-leucine, oleamide, lysoPC (16:0), and lysoPC (18:0) in the whole-grain group showed greater reductions compared with those of the control group. Changes in plasma metabolites were not significantly different between the two groups. Changes in PBMC Lp-PLA(2) activity positively correlated with changes in L-leucine, oleamide, lysoPC (16:0), lysoPC (18:0), glucose, and ox-LDL, and negatively correlated with changes in LDL particle size. CONCLUSIONS: This study showed that dietary intervention in prediabetic or type-2 diabetic patients had a greater effect on PBMC Lp-PLA(2) activity and metabolites compared with those of plasma metabolites. TRIAL REGISTRATION: NCT02191644