Mango Consumption Is Associated with Increased Insulin Sensitivity in Participants with Overweight/Obesity and Chronic Low-Grade Inflammation

<b>Background/Objectives:</b> Chronic low-grade inflammation is associated with insulin resistance and poor glycemic control, leading to the development of type 2 diabetes mellitus (T2DM). The present study investigated the effect of regular mango intake on inflammation and insulin sensitivity in participants with overweight or obesity and chronic low-grade inflammation. <b>Methods:</b> A human clinical study was performed using a randomized, controlled, two-arm, parallel design with a 2 h oral glucose tolerance test (OGTT) administered before and after 4 weeks (4 W) of mango or control product intake (1 cup/twice a day). Fasting and time course blood sampling for 2 h post-OGTT were analyzed for effects on plasma metabolic and inflammation endpoints using analysis of covariance and repeated-measure approaches (SAS 9.4). <b>Results:</b> Forty-eight adults (37.6 ± 2.8 years, 30.5 ± 4.1 BMI kg/m²) completed the study. Markers of inflammation (IL-6, TNFα, hs-CRP) were not different at the end of 4 W (<i>p</i> > 0.05). The intervention did not significantly influence fasting glucose concentrations; however, insulin was significantly lowered with the mango compared to the control intervention (8.2 ± 1.2 vs. 15.3 ± 1.2 µIU/mL respectively, <i>p</i> = 0.05). Furthermore, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), along with the disposition index (DI), was significantly improved in the mango compared to the control interventions (HOMA-IR, 2.28 ± 1.19 vs. 4.67 ± 1.21, <i>p</i> = 0.03; DI, 2.76 ± 1.02 vs. 5.37 ± 1.03, <i>p</i> = 0.04). Mean insulin concentrations were also significantly lower at W4 compared to W0 after the OGTT in the mango vs. control intervention (intervention × week effect, <i>p</i> = 0.04). Relative expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), a gene regulating endogenous antioxidant defense, was non-significantly increased twofold in the mango intervention (W4 vs. W0). <b>Conclusions:</b> Collectively, the data suggest that mango intake increased insulin sensitivity in individuals with chronic low-grade inflammation, possibly through activating Nrf-2 genes and increasing cellular antioxidant status. The data warrant further research on consuming mango fruit as part of a dietary pattern to address insulin resistance and the mechanisms underpinning the actions of mango intake.