flavan-3-ol and Diabetes-Mellitus--Type-2

Type 2 diabetes is an increasing health concern worldwide. Both genetic and environmental risk factors as improper dietary habits or physical inactivity are known to be crucial in the pathogenesis of type 2 diabetes. Polyphenols are a group of plant-derived compounds with anti-inflammatory and antioxidant properties that are associated with a low prevalence of metabolic conditions characterized by insulin resistance, including obesity, diabetes, and hypertension. Moreover, there is now full awareness that foods that are rich in phytochemicals and polyphenols could play an important role in preserving human cardiovascular health and substantial clinical evidence indicates that regular dietary consumption of such foods affects favorably carbohydrate metabolism. This review briefly summarizes the evidence relating dietary patterns rich in polyphenols with glucose metabolism and highlights the potential benefits of these compounds in the prevention of type 2 diabetes.

Topics: Anthocyanins; Diabetes Mellitus, Type 2; Diet; Flavonoids; Humans

Diet is one of the pillars in the prevention and management of diabetes mellitus. Particularly, eating patterns characterized by a high consumption of foods such as fruits or vegetables and beverages such as coffee and tea could influence the development and progression of type 2 diabetes. Flavonoids, whose intake has been inversely associated with numerous negative health outcomes in the last few years, are a common constituent of these food items. Therefore, they could contribute to the observed positive effects of certain dietary habits in individuals with type 2 diabetes. Of all the different flavonoid subclasses, flavan-3-ols are consumed the most in the European region. However, a large proportion of the ingested flavan-3-ols is not absorbed. Therefore, the flavan-3-ols enter the large intestine where they become available to the colonic bacteria and are metabolized by the microbiota. For this reason, in addition to the parent compounds, the colonic metabolites of flavan-3-ols could take part in the prevention and management of diabetes. The aim of this review is to present the available literature on the effect of both the parent flavan-3-ol compounds found in different food sources as well as the specific microbial metabolites of diabetes in order to better understand their potential role in the prevention and treatment of the disease.

Topics: Diabetes Mellitus, Type 2; Dietary Supplements; Feeding Behavior; Female; Flavonoids; Gastrointestinal Microbiome; Humans; Male; Nutritional Physiological Phenomena

Obesity has major adverse consequences on human health contributing to the development of, among others, insulin resistance and type 2 diabetes, cardiovascular disease, non-alcoholic fatty liver disease, altered behavior and cognition, and cancer. Changes in dietary habits and lifestyle could contribute to mitigate the development and/or progression of these pathologies. This review will discuss current evidence on the beneficial actions of the flavan-3-ol (-)-epicatechin (EC) on obesity-associated comorbidities. These benefits can be in part explained through EC's capacity to mitigate several common events underlying the development of these pathologies, including: i) high circulating levels of glucose, lipids and endotoxins; ii) chronic systemic inflammation; iii) tissue endoplasmic reticulum and oxidative stress; iv) insulin resistance; v) mitochondria dysfunction and vi) dysbiosis. The currently known underlying mechanisms and cellular targets of EC's beneficial effects are discussed. While, there is limited evidence from human studies supplementing with pure EC, other studies involving cocoa supplementation in humans, pure EC in rodents and in vitro studies, support a potential beneficial action of EC on obesity-associated comorbidities. This evidence also stresses the need of further research in the field, which would contribute to the development of human dietary strategies to mitigate the adverse consequences of obesity.

Topics: Animals; Blood Glucose; Cardiovascular Diseases; Catechin; Comorbidity; Diabetes Mellitus, Type 2; Dysbiosis; Dyslipidemias; Endoplasmic Reticulum; Endotoxins; Flavonoids; Humans; Inflammation; Insulin Resistance; Lipid Metabolism; Mental Disorders; Mitochondria; Non-alcoholic Fatty Liver Disease; Obesity; Oxidative Stress

Although available data suggest that some dietary flavan-3-ol sources reduce cardiometabolic risk, to our knowledge no review has systematically synthesized their specific contribution.. We aimed to examine, for the first time, if there is consistent evidence that higher flavan-3-ol intake, irrespective of dietary source, reduces cardiometabolic risk.. MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched for prospective cohorts and randomized controlled trials (RCTs) published from 1946 to March 2019 on flavan-3-ol intake and cardiovascular disease (CVD) risk. Random-effects models meta-analysis was used. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed the strength of evidence.. Of 15 prospective cohorts (23 publications), 4 found highest compared with lowest habitual intakes of flavan-3-ols were associated with a 13% reduction in risk of CVD mortality and 2 found a 19% reduction in risk of chronic heart disease (CHD) incidence. Highest compared with lowest habitual intakes of monomers were associated with a reduction in risk of type 2 diabetes mellitus (T2DM) (n = 5) and stroke (n = 4) (10% and 18%, respectively). No association was found for hypertension. Of 156 RCTs, flavan-3-ol intervention resulted in significant improvements in acute/chronic flow-mediated dilation (FMD), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), LDL and HDL cholesterol, triglycerides (TGs), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). All analyses, except HbA1c, were associated with moderate/high heterogeneity. When analyses were limited to good methodological quality studies, improvements in TC, HDL cholesterol, SBP, DBP, HOMA-IR, and acute/chronic FMD remained significant. In GRADE evaluations, there was moderate evidence in cohort studies that flavan-3-ol and monomer intakes were associated with reduced risk of CVD mortality, CHD, stroke, and T2DM, whereas RCTs reported improved TC, HDL cholesterol, SBP, and HOMA-IR.. Available evidence supports a beneficial effect of flavan-3-ol intake on cardiometabolic outcomes, but there was considerable heterogeneity in the meta-analysis. Future research should focus on an integrated intake/biomarker approach in cohorts and high-quality dose-response RCTs. This review was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42018035782.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Flavonoids; Glucose; Humans; Insulin Resistance; Lipids; Prospective Studies; Randomized Controlled Trials as Topic

This review summarizes the results on flavonoid intakes and the development of type 2 diabetes and cardiovascular diseases.. Recent advances in food composition databases have allowed the evaluation of a more comprehensive range of flavonoids in epidemiological studies. In addition, the number of randomized trials of flavonoid-rich foods has increased rapidly. Results from both cohort studies and randomized trials suggest that anthocyanidins from berries and flavan-3-ols from green tea and cocoa may lower the risk of type 2 diabetes and cardiovascular diseases. Meta-analyses of randomized trials indicate that the strongest evidence exists for a beneficial effect of green tea on LDL-cholesterol and a beneficial effect of flavan-3-ol-rich cocoa on endothelial function and insulin sensitivity. Few randomized trials had a long duration or evaluated pure flavonoid compounds.. Evidence from cohort studies and randomized trials suggest beneficial effects of food sources of anthocyanidins (berries) and flavan-3-ols (green tea and cocoa) on cardiovascular health. These findings need to be confirmed in long-term randomized trials, and evaluation of pure compounds will be important to establish what specific flavonoids and doses are effective.

Topics: Anthocyanins; Antioxidants; Cacao; Camellia sinensis; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus, Type 2; Eating; Endothelium, Vascular; Feeding Behavior; Flavonoids; Flavonols; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

Endothelial dysfunction plays an important role in development and progression of atherosclerosis and may also contribute to the pathogenesis of type 2 diabetes. This review summarizes recent findings on the effects of vitamin D, antioxidant vitamins, polyphenols, polyphenol-rich foods, dietary component combinations and healthy diets on endothelial function.. Dietary patterns rich in fruit, vegetables, fish and nuts appear to have beneficial effects on endothelial function. With regard to specific foods, cacao and green tea consumption have been associated with improvement in endothelial function and this seems to be due to their flavan-3-ol (catechins and epigallocatechin gallate) content. The evidence for beneficial effects of other foods such as citrus fruit, apples and red wine is less consistent. Recent studies have also suggested beneficial effects of vitamin D and anthocyanins on endothelial function and have provided more insight into potential mechanisms underlying the effect of diet on endothelial function.. The currently available evidence supports beneficial effects of various dietary compounds on endothelial function. However, in order to obtain strong evidence for relevant health effects that can be used for specific dietary recommendations, more long-term studies using well characterized diets/supplements in a large number of individuals are needed.

Topics: Cacao; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Endothelium, Vascular; Flavonoids; Fruit; Humans; Tea; Vegetables

In healthy participants, short-term flavan-3-ol and isoflavone intakes improve vascular function; however, the potential combined benefit of these compounds on atherosclerosis progression remains unclear for those at elevated risk of cardiovascular disease.. The objective was to examine whether combined isoflavone and flavan-3-ol intake alters vascular function in postmenopausal women with type 2 diabetes mellitus (T2DM).. A double-blind, parallel-design, placebo-controlled 1-y trial was conducted in postmenopausal T2DM patients randomly assigned to a split dose of 27 g flavonoid-enriched chocolate/d [850 mg flavan-3-ols (90 mg epicatechin) + 100 mg isoflavones (aglycone equivalents)/d] or matched placebo. Intima-media thickness of the common carotid artery (CCA-IMT), pulse wave velocity (PWV), augmentation index, blood pressure (BP), and vascular biomarkers were assessed.. A total of 93 patients completed the trial. Overall, the flavonoid intervention did not significantly change CCA-IMT, augmentation index, or BP, but pulse pressure variability improved (flavonoid: -0.11 ± 0.07 mm Hg/min; placebo: 0.10 ± 0.11 mm Hg/min; P = 0.04). In a subgroup with PWV data, net improvements were observed [flavonoid (n = 18): -0.07 ± 0.38 m/s; placebo (n = 17): 0.68 ± 0.25 m/s; P = 0.01], which equated to a 10% CV risk reduction. Equol producers (n = 17) had larger reductions in diastolic BP, mean arterial pressure, and PWV (-2.24 ± 1.31 mm Hg, -1.24 ± 1.30 mm Hg, and -0.68 ± 0.40 m/s, respectively; P < 0.01) compared with non-equol producers (n = 30).. Although the 1-y intervention did not change CCA-IMT or BP, clinically relevant improvements in arterial stiffness were observed; equol producers were particularly responsive. Flavonoids may augment existing therapeutic strategies to reduce cardiovascular disease risk in postmenopausal T2DM patients, and longer studies are needed to examine the effects on atherosclerosis progression. This trial was registered at clinicaltrials.gov as NCT00677599.

Topics: Aged; Arterial Pressure; Atherosclerosis; Biomarkers; Carotid Artery, Common; Carotid Intima-Media Thickness; Diabetes Mellitus, Type 2; Diet; Disease Progression; Double-Blind Method; Female; Flavonoids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoflavones; Middle Aged; Patient Compliance; Postmenopause; Pulse Wave Analysis; Vascular Stiffness

To assess the effect of dietary flavonoids on cardiovascular disease (CVD) risk in postmenopausal women with type 2 diabetes on established statin and hypoglycemic therapy.. Despite being medicated, patients with type 2 diabetes have elevated CVD risk, particularly postmenopausal women. Although dietary flavonoids have been shown to reduce CVD risk factors in healthy participants, no long-term trials have examined the additional benefits of flavonoids to CVD risk in medicated postmenopausal women with type 2 diabetes. We conducted a parallel-design, placebo-controlled trial with type 2 diabetic patients randomized to consume 27 g/day (split dose) flavonoid-enriched chocolate (containing 850 mg flavan-3-ols [90 mg epicatechin] and 100 mg isoflavones [aglycone equivalents)]/day) or matched placebo for 1 year.. Ninety-three patients completed the trial, and adherence was high (flavonoid 91.3%; placebo 91.6%). Compared with the placebo group, the combined flavonoid intervention resulted in a significant reduction in estimated peripheral insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR] -0.3 ± 0.2; P = 0.004) and improvement in insulin sensitivity (quantitative insulin sensitivity index [QUICKI] 0.003 ± 0.00; P = 0.04) as a result of a significant decrease in insulin levels (-0.8 ± 0.5 mU/L; P = 0.02). Significant reductions in total cholesterol:HDL-cholesterol (HDL-C) ratio (-0.2 ± 0.1; P = 0.01) and LDL-cholesterol (LDL-C) (-0.1 ± 0.1 mmol/L; P = 0.04) were also observed. Estimated 10-year total coronary heart disease risk (derived from UK Prospective Diabetes Study algorithm) was attenuated after flavonoid intervention (flavonoid +0.1 ± 0.3 vs. placebo 1.1 ± 0.3; P = 0.02). No effect on blood pressure, HbA(1c), or glucose was observed.. One-year intervention with flavan-3-ols and isoflavones improved biomarkers of CVD risk, highlighting the additional benefit of flavonoids to standard drug therapy in managing CVD risk in postmenopausal type 2 diabetic patients.

Topics: Aged; Cardiovascular Diseases; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Female; Flavonoids; Humans; Insulin Resistance; Isoflavones; Lipoproteins; Middle Aged; Postmenopause

The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model.. (ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8-h pharmacokinetic study was performed. After 24 h, a second dose of SGP was administered and 1 h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished C. Diabetes may alter the overall bioavailability of some polyphenols in plasma and brain in part due to higher urinary clearance.

Topics: Animals; Anthocyanins; Biological Availability; Blood Glucose; Brain; Catechin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Flavonoids; Grape Seed Extract; Male; Polyphenols; Quercetin; Rats; Rats, Zucker; Resveratrol; Stilbenes; Tandem Mass Spectrometry; Vitis

Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile: 0.81; 95% CI: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% CI: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% CI: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.

Topics: Adult; Diabetes Mellitus, Type 2; Diet; Europe; Female; Flavonoids; Flavonols; Follow-Up Studies; Humans; Incidence; Life Style; Male; Middle Aged; Motor Activity; Multivariate Analysis; Nutritional Status; Proanthocyanidins; Proportional Hazards Models; Prospective Studies; Risk Factors; Socioeconomic Factors; Surveys and Questionnaires; White People