Effects of Red Raspberry Polyphenols and Metabolites on Biomarkers of Inflammation and Insulin Resistance in Prediabetes and Type 2 Diabetes

Abstract

Berry fruits are rich sources of polyphenolic compounds (PCs), which can promote health benefits. Anthocyanin concentrations of red raspberry (RR)(Rubus idaeus) extracts were determined to be a total of 887.6 ± 262.8 μg/g cyanidin-3-sophoroside (C3S) equivalents with C3S being the most prevalent. Ellagitannin analysis by MALDI-TOF indicated sanguiin H-6 and lambertianin C were the major ellagitannins present in RR. To explore the efficacy of RR in modulating diabetes, seven type 2 diabetes mellitus (T2DM) and two pre-diabetic patients were given drinks delivering one RR serving (123 g) per day in a smoothie for two weeks. Blood samples were drawn at baseline (BSL) and post-feeding (PF) days. The samples were analyzed for phenolic metabolites, and for both inflammation and insulin resistance biomarkers. Two urolithin conjugates, i.e. urolithin A glucuronide (Uro-A glur) and urolithin A sulfate (Uro-A sulf) were found in 7 of the 9 patients’ plasma samples at nanomolar concentrations on PF day whereas anthocyanin-derived metabolites such as protocatechuic acid (PCA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were present at higher but not statistically significant levels on both groups at PF day when compared to BSL. Results indicated significant reductions in hsCRP (p= 0.01), and on insulin resistance where a statistical trend on HOMA-IR (p=0.0584) for T2DM patients was seen. DOPAC, a metabolite from anthocyanin and quercetin consumption in RR, when incubated at 1-100 µM did not stimulate insulin secretion in INS-1 rat pancreatic cells. Increases and decreases were observed on the cytokines analyzed by multiplex assay, yet, none was significant on either group. This study demonstrates the potential of RR to modulate levels of biomarkers of inflammation and insulin resistance in diabetic and prediabetic patients.