Diabetic cardiomyopathy (DCM) is one of the main causes of mortality among diabetic patients, with oxidative stress and inflammation major contributors to its development. Dietary flavonoids show strong antioxidant and anti-inflammatory activities, although their potential additive outcomes in combination with antidiabetic drugs have been scarcely explored. The present study investigates the cardioprotective effects of a cocoa–carob blend (CCB) diet, rich in flavonoids, alone or in combination with metformin, in the development of DCM. Zucker diabetic fatty rats (ZDF) were fed with a CCB rich-diet or a control diet, with or without metformin for 12 weeks. Glucose homeostasis, cardiac structure and function, and oxidative and inflammatory biomarkers were analysed. CCB improved glucose homeostasis, and mitigated cardiac dysfunction, hypertrophy, and fibrosis in ZDF rats. Mechanistically, CCB counteracted oxidative stress in diabetic hearts by down-regulating NADPH oxidases, reducing reactive oxygen species (ROS) generation and modulating the sirtuin-1 (SIRT1)/ nuclear factor E2-related factor 2 (Nrf2) signalling pathway, overall improving antioxidant defence. Moreover, CCB suppressed inflammatory and fibrotic reactions by inhibiting nuclear factor kappa B (NFκB) and pro-inflammatory and pro-fibrotic cytokines. Noteworthy, several of these effects were further improved in combination with metformin. Our results demonstrate that CCB strongly prevents the cardiac remodelling and dysfunction observed in diabetic animals, highlighting its potential, alone or in adjuvant therapy, for treating DCM.

Epicatechin (EC) and main colonic phenolic acids derived from flavonoid intake have been suggested to exert healthful effects, although their mechanism of action remains unknown. Heart damage is highly prevalent...

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The aim of this study was to determine whether grape polyphenols have a "second-meal effect", modulating glucose and lipid elevations in the postprandial period after two successive meals in subjects with obesity.Methods. A randomized, double-blind, placebo-controlled, acute clinical trial was conducted. Twenty-five obese subjects (BMI = ≥30 and <40 kg/m 2 ) were randomly divided into two groups. At an initial visit, blood was collected in a fasting state and the subjects received breakfast and 46 g of either grape powder (equivalent to 252 g fresh grapes) or placebo, both solved in water. Lunch was provided 5 h later and then blood was collected after 0, 30, 60, 120, 180, 240, 300, 330, 360 and 420 min. Two weeks later, at a second visit, the subjects received the other powder. The following were determined: glucose, insulin, triglycerides, uric acid, blood count, hemoglobin, viscosity, antioxidant capacity, and satiety perception.Results. Postprandial increases were observed as expected in, for example, glucose and triglycerides after breakfast and lunch. The grape powder supplementation did not cause any significant modification compared to placebo, in these parameters; nor did it significantly modify plasma antioxidant capacity in the 6 h postprandial period.3 Discussion. Single grape powder supplementation did not modify postprandial responses in obese subjects, probably because the polyphenol dose was insufficient to induce such an effect. The result of a combination of grape with other polyphenol-rich products or chronic supplementation with grape powder on postprandial responses remains to be elucidated.Trial registration number. www.clinicaltrials.gov, NCT03741218