Growing evidence from animal studies supports the anti-diabetic properties of some dietary polyphenols, suggesting that dietary polyphenols could be one dietary therapy for the prevention and management of Type 2 Blutzucker Stress. This review aims to address the potential mechanisms of action of dietary polyphenols in the regulation of glucose homeostasis and insulin sensitivity Blutzucker Stress on in vitro and in vivo studies, and Blutzucker Stress provide a comprehensive overview of the anti-diabetic effects of commonly consumed dietary polyphenols including polyphenol-rich mixed diets, tea and coffee, chocolate and cocoa, cinnamon, grape, pomegranate, red wine, berries and olive oil, with a focus on human clinical trials.
However, human epidemiological and intervention studies have shown inconsistent results. Further intervention studies are essential to clarify the conflicting findings and confirm or refute the Blutzucker Stress effects of dietary polyphenols.
Type 2 diabetes T2D is a chronic Blutzucker Stress of metabolic dysregulation, most notably abnormal glucose metabolism, accompanied by complications including cardiovascular disease, retinopathy, nephropathy, neuropathy, leg ulcers and gangrene [ 1 ]. Inmillion people were estimated to have diabetes globally and this number is projected to be million by [ 2 ]. Identification of modifiable lifestyle factors including dietary factors that reduce the incidence of T2D is a vital area of research [ 34 Blutzucker Stress.
One dietary factor of interest is consumption Blutzucker Stress polyphenol-rich foods. Dietary polyphenols have been suggested to lower the risk of T2D [ 567 ].
This review aims Blutzucker Stress summarize relevant epidemiological and clinical studies linking polyphenol-rich foods to the risk of T2D, and Blutzucker Stress describe the Blutzucker Stress mechanisms of action of polyphenol-rich foods through which these effects are mediated. Polyphenols are a Blutzucker Stress and heterogeneous group of phytochemicals containing phenol rings [ 6 ].
Several hundred different polyphenols are found in plant-based foods including vegetables particularly, broccoli, onion and cabbagefruits grapes, pears, apples, cherries and various berries contain up to — mg polyphenols per g fresh weightlegumes soybeancereals, plant-derived beverages and chocolate [ 5Blutzucker Stress9 ].
Approximately mg of Blutzucker Stress are identified in a cup of coffee or tea or a glass of red wine [ 89 ]. Polyphenols are divided into flavonoids, phenolic acids, stilbenes, and lignans [ 9 ]. Flavonoids include flavones, flavonols flavanols, flavanones, isoflavones, and anthocyanins [ 7810 ]. The most common phenolic acids are caffeic acid present in many fruits and vegetables, Blutzucker Stress often esterified with quinic acid as in chlorogenic acid, which is a Blutzucker Stress phenolic compound in coffee and ferulic acid present in cereals which is esterified to hemicelluloses in the cell wall.
The best studied stilbene is resveratrol in grapes, grape products and red wine [ 10 ]. The richest source of lignans is linseed present mainly as secoisolariciresinol up to 3.
Chemical structures and dietary sources of different groups of polyphenols are shown in Figure 1. Chemical structures and Blutzucker Stress sources of different groups of polyphenols. Flavonoids Blutzucker Stress most abundant in four groups of dietary polyphenols and share a basic structure. Resveratrol is one of a subclass of stilbenes. Some phenolic acids are caffeic acid, chlorogenic acid and ferulic acid. Flavones, flavonols, flavanones, flavanols, isoflavone and anthocyanidins are main Blutzucker Stress of flavonoids.
Typically, quercetin Blutzucker Stress rich in onion, tea, and apple. Hesperetin is rich in citrus fruits, Blutzucker Stress and daidzein are rich in soybeans.
Anthocyanins including cyanidins contribute colour to many red fruits such as strawberry, raspberry and blackcurrant [ 810 ]. Epidemiological studies support favourable effects Blutzucker Stress polyphenol-rich diets in preventing and managing T2D Blutzucker Stress 6 ]. Metabolites of flavanols and ferulic acid were not associated with T2D risk in either period [ 11 ]. A Finnish study of 10, men and women with T2D cases showed that intakes of apples hazard ratio—HR 0. An inverse Blutzucker Stress remained after adjustment for body mass index BMI or weight [ 1314 ].
Inconsistent findings might be explained due to the use Blutzucker Stress the older, less complete versions of the United States Department of Agriculture USDA database [ 1215 ] and misclassification of intake in the baseline questionnaires [ 14 ]. Much of the epidemiological data is based on reported food intake rather than blood or urine measures of polyphenol metabolites and is thus relatively unreliable compared with more objective measures.
Epidemiological studies showed a fairly consistent association between coffee caffeinated and decaffeinated [ 1617181920 ] or green tea Blutzucker Stress 21 ] consumption and a lower risk of T2D in a dose-response manner in most studies [ 161718192021 ] except [ 22 ].
Both caffeinated and decaffeinated coffee were associated with Blutzucker Stress lower risk of T2D [ 16 ]. A retrospective cohort study of 17, Japanese men and women aged 40—65 years, based on completed five-year follow-up questionnaire found RRs of 0.
The consumption of black or oolong teas was Blutzucker Stress associated with the risk of T2D [ 21 ]. These inverse associations Blutzucker Stress more prominent in women and in overweight men [ 21 ]. Coffee intake of 4. The relative amount of Blutzucker Stress vs. Positive effects Blutzucker Stress coffee and tea on a lower risk of T2D were independent of weight or BMI [ 16Blutzucker Stress20212224 ].
Observational studies have shown that higher coffee consumption Blutzucker Stress associated with decreased fasting insulin [ 26 ] and 2-h Blutzucker Stress glucose [ 27 ], and homeostatic model assessment levels [ 26Blutzucker Stress29 ], increased insulin sensitivity [ 30 ], but other studies have shown no association of coffee consumption with fasting insulin [ 2731 ] or homeostasis model assessment of insulin resistance HOMA—IR [ 31 ].
Polyphenols may suppress glucose release from the liver, and improve glucose uptake in peripheral tissues by modulating intracellular signalling [ 6 ].
Polyphenols have antioxidant activity and can inhibit advanced glycation endproduct AGE formation [ 5 ]. Glucose is taken into cells via transporters, predominately sodium-dependent glucose transporter SGLT1 located in the brush border membrane at the apical side of enterocytes [ 34 ].
Inhibition of glucose transport has been shown Blutzucker Stress flavonoids and Blutzucker Stress acids [ 4243444546 ]. Enhanced insulin-mediated glucose uptake in vitroa glucose transporter 4-mediated process, has been shown with dietary polyphenols including epicatechin [ 47 ], epigallocatechin O -gallate EGCG [ 48 Blutzucker Stress, grape seed-derived procyanidins [ 4950 ], bitter melon [ 51 ], blueberry [ 52 ], canna indica root [ 53 Blutzucker Stress and black soy bean [ 54 ].
This activation was accompanied by the up-regulation of glucose transporter 4 GLUT4 in skeletal muscle and the down-regulation of gluconeogenesis in the liver in type Blutzucker Stress diabetic mice [ 54 ]. Cinnamon has shown potential to promote insulin signalling, and GLUT4 translocation Blutzucker Stress Swiss albino mouse embryo fibroblast line 3T3-L1 adipocytes [ 55 ], and increase glucose uptake in insulin resistant rats induced by a high fructose diet [ 5657 ].
Blutzucker Stress majority of the ingested polyphenols reach the colon, thereafter undergoing intensive metabolism prior to absorption [ 5859 ]. Some polyphenols are thought to exert a prebiotic effect by stimulating the growth and activity of some bacteria in the digestive tract [ 59 ].
After absorption, polyphenols undergo phase I and II biotransformation sulfation, glucuronidation, methylation and glycine-conjugation by enterocytes in Blutzucker Stress liver to increase hydrophilicity favouring urinary secretion [ 58 ].
Polyphenol metabolites derived from liver metabolism interact with adipose tissue, pancreas, muscle and liver, and Blutzucker Stress exert anti-diabetic effects [ 59 ]. Absorption of polyphenols can be affected by dosage, size of phenolic compound, prior diet, food matrix, gender Blutzucker Stress differences in the gut microbial populations [ 59 ].
A few clinical trials [ 626364656667 ] have shown the potential Blutzucker Stress effects of dietary polyphenols to increase the population of Bifidobacteria. In a randomized, controlled, double-blind, crossover study of 22 health volunteers [ 62 Blutzucker Stress, the daily consumption of mg cocoa flavanols for four weeks significantly increased the growth of Lactobacillus spp.
Similarly, the daily consumption of red wine polyphenols for four weeks modulated the growth of gut microbiota [ 66 ] by significantly increasing Bifidobacterium and EnterococcusPrevotellaBacteroidesBacteroides uniformisEggerthella lentaand Blautia coccoides-Eubacterium rectale groups compared with baseline but there was no control drink for Blutzucker Stress.
Improvements in cholesterol and CRP levels were Blutzucker Stress with changes in the Bifidobacteria amount [ 66 ]. Daily consumption of 25 Blutzucker Stress of wild blueberry powder drink for six weeks increased Blutzucker Stress spp. A proanthocyanidin-rich extract from grape seeds administered to nine healthy adults for two weeks significantly increased Bifidobacterium but no control material was provided to volunteers [ 64 ].
Chronic high glucose exposure directly increased intracellular reactive oxygen species ROS generation and disturbed mitochondrial Blutzucker Stress, uncoupling ATP generation and impairing insulin secretion [ 69 ]. Moreover, chronic high glucose exposure suppressed AMPK activity leading to increased lipogenesis [ 69 ].
The liver is a key regulator of blood glucose levels in coordination with muscle and adipose tissues [ 6 ]. In the postprandial state, the liver stores glucose as glycogen via the glycogenesis pathway involving glucokinase Blutzucker Stress which is a key enzyme in the regulation of glucose utilization in the liver, and glycogen synthase GS. Under fasting conditions, the liver produces glucose via two routes—either glycogenolysis or gluconeogenesis involving pyruvate carboxylase, phosphoenolpyruvatecarboxykinase PEPCKfructose-1,6-bisphosphatase, and glucosephosphatase [ 6 ].
Suppressed hepatic glucose production appears to account for decreased glucose levels in EGCG and green tea feeding and in vitro studies [ 747576 ]. In the rodent study [ 76 ] of EGCC supplementation of either 0. Moreover, in H4IIE hepatoma cells, EGCC downregulated genes involved in gluconeogenesis and the synthesis of fatty acid, triacylglycerol and cholesterol, whereas genes involved in glycolysis phosphofructokinase and glucose transport glucose transporter 1 were increased [ 76 Blutzucker Stress.
Supplementation of the soy isoflavones genistein and daidzein 0. This mechanism of citrus flavonoid is very similar to the mechanism of thiazolidinediones [ 78 ]. Low-grade inflammation and obesity-induced oxidative stress in the mitochondria may be partly responsible for insulin resistance. Elevated proinflammatory cytokines can alter metabolic homeostatic control systems leading to T2D Blutzucker Stress 81 ]. Dietary cyanidin 3-glucoside 0. Supplementation of a high-fat diet with 0.
A summary of possible mechanisms of Blutzucker Stress is shown in Figure 2. The summary of potential mechanisms linking dietary polyphenol metabolites to improved glucose homeostasis. See the text for more details. There are a few clinical studies investigating the effects of specific polyphenols or food products rich in polyphenols in reducing the risk of insulin resistance [ 6 ]. In a meta-analysis of green tea or green tea extract of seven randomised controlled trials, the consumption of green tea did not decrease the levels of fasting plasma glucose, fasting serum insulin, 2-h oral glucose tolerance test OGTTglucose, glycated hemoglobin HbA1c or HOMA—IR index [ 90 ].
However the authors Blutzucker Stress that limitations of the studies included the small sample sizes, poor quality and low evidence levels of the included studies. In contrast, another meta-analysis of 17 randomised controlled trials including seven high quality studies and 10 low quality studies, demonstrated that green tea had favourable effects significantly reducing the fasting glucose and HbA1c by Blutzucker Stress. This study attributed these findings to measures of glucose control or insulin sensitivity not coming from primary outcomes, limited high quality studies, and concealment of null Blutzucker Stress in most selected studies [ 91 ].
In subgroup analyses, the glucose-lowering effect was observed when the duration of follow-up was over a median of 12 weeks. This finding suggested that longer trials were required to support favourable effects of green tea Blutzucker Stress on glycemic control [ 92 ]. In summary, given the mixed results from interventions in contrast to epidemiological studies, it is still unclear if polyphenol-rich green tea has anti-diabetic effects.
A randomized cross over study investigating the effect of a single dose of espresso caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and insulin Blutzucker Stress Matsuda index during an OGTT in 18 habitual coffee drinkers with T2D showed no difference in area Blutzucker Stress the Blutzucker Stress AUC Blutzucker Stress, glucose or insulin sensitivity [ 31 ].
However, a three-way, randomized, crossover study of nine healthy subjects [ 93 ] showed that Blutzucker Stress acid in coffee acutely modulated gastrointestinal hormone secretion and glucose uptake [ 93 ]. The consumption of 25 g glucose in either mL water control or mL caffeinated or decaffeinated coffee equivalent to 2.
This finding suggested that chlorogenic acid in coffee decreased the rate of intestinal absorption of glucose or slowed gastric empting [ 93 ]. Overall, there is little evidence available to assess the effect of coffee on glucose homeostasis. There was no effect on fasting glucose and HbA1c [ 94 ]. Dark Blutzucker Stress g bar containing approximately mg of Blutzucker Stress for 15 days decreased blood pressure Blutzucker Stress improved insulin sensitivity in healthy individuals as demonstrated by decreasing HOMA—IR 0.
A four-week consumption of dark chocolate containing mg polyphenols reduced blood pressure BPBlutzucker Stress glucose and HOMA—IR in lean and overweight females [ 98 ] compared with 20 g of placebo dark chocolate containing negligible polyphenol but similar nutritional composition.
Consumption of cocoa flavanols mg for 12 weeks also improved insulin sensitivity in overweight and obese individuals compared with a low-flavanol cocoa drink [ 99 ]. In contrast, consumption of flavanol-rich cocoa drink mL twice a day, containing approximately mg flavanols for two weeks did not improve insulin resistance or blood pressure in people with essential hypertension [ Blutzucker Stress.
Daily consumption of 25 g dark chocolate for eight weeks did not improve fasting glucose, insulin and HbA1c levels in hypertensive diabetic subjects compared with 25 g Blutzucker Stress chocolate consumption [ ]. In summary, given conflicting Blutzucker Stress in interventions, current Blutzucker Stress is insufficient to recommend chocolate and cocoa for glycemic control. Therefore, large placebo controlled trials with good quality designs are required to clarify the effects of cocoa polyphenols.
Cinnamon is known to contain polyphenols such as catechin, procyanidin, cinnamtannin trans-cinnamic acid and flavones cinnamaldehyde and trans-cinnamaldehyde [ 5, ].