## 4 The Antidiabetic Effects of Dietary Phenolic Compounds: Preclinical and Clinical Evidence  
Preclinical experiments using different animal models of type 1 or type 2 diabetes (T1D or T2D, respectively) have demonstrated the benefits of dietary phenolic compounds on glucose homeostasis. For instance, the polyphenol resveratrol partially prevents and reverts the onset of diabetes [120] in NOD mice, a non-obese polygenic model for autoimmune T1D, and improves glucose tolerance and insulin sensitivity in a hypoinsulinemic diabetic animal model induced by streptozotocin (STZ) [121]. Moreover, studies conducted in T2D animal models, e.g., hyperinsulinemic and hyperglyemic mice fed hypercaloric diets, i.e., diet-induced obese mice, have demonstrated that dietary supplementation with polyphenol-rich cranberry extract induces both preventive [122] and therapeutic [123] benefits on the glucose metabolism such as improved glucose oral tolerance and insulin sensitivity and reduced glucose-induced hyperinsulinemia. Additionally, preclinical trials conducted in genetic models of T2D have also demonstrated the glucoregulatory properties of phenolic compounds. For instance, dietary supplementation with aspalathin, which belongs to the dihydrohalcone subgroup of phenolic compounds, improves glucose tolerance in hyperphagic and overweight leptin-deficient type 2 diabetic mice (ob/ob) [124]. Moreover, interventional studies in spontaneous animal models of T2D such as obese mice with a homozygous mutation in leptin receptor (db/db mice) or non-obese Goto kakizaki rats have revealed that the phenolic compound resveratrol preserves the abundance of pancreatic \(\beta\) cells, reduces fasting blood glucose levels and improves glucose tolerance [125; 126]. Moreover, green tea phenolic compounds reduce fasting glucose and insulin levels and improve insulin sensitivity in obese and T2D Zucker fatty rats [127]. The glucoregulatory effects of phenolic compounds have also been documented in humans. In healthy individuals, the intake of a drink rich in phenolic compounds from red grape pomace reduces postprandial insulin and increases insulin sensitivity [128]. In a cross-over controlled randomised interventional trial conducted on subjects with metabolic syndrome, it has been demonstrated that eight weeks of polyphenol dietary supplementation improved whole-body glucose clearance after an oral glucose load and enhanced early insulin secretion [129]. Moreover, grape phenolic compounds dietary supplementation prevents the fructose-induced decrease in hepatic insulin sensitivity and glucose infusion rate in healthy obese and overweight subjects with a risk of T2D [130]. A 2-month resveratrol intervention also reduced fasting glucose and oxidative stress in T1D patients [131]. Nevertheless, phenolic compounds such as resveratrol do not show additive benefits with the glucose-lowering medication metformin [132], which highlights the clinical applicability of phenolic compounds in drug naive diabetic patients or individuals with prediabetes. Table 3 highlights the pleiotropic effects of dietary intervention with phenolic compounds. Indeed, these molecules induce diverse benefits including the restoration of postprandial insulin secretion, the improvement of hepatic insulin sensitivity, or the reduction of oxidative stress and dyslipidemia. Importantly, the clinical relevance of these compounds is supported by studies in humans. Table 3 also indicates important information on different dietary interventions conducted in humans and rodents such as the duration and the dose employed. Molecular Mechanisms Underlying the Benefits of Phenolic Compounds in Glucose Homeostasis  
The mechanisms through which dietary phenolic compounds can reduce postprandial glycan have been explored in several _in vivo_ and _in vitro_ preclinical trials.