Effets d'une prise unique de flavanols du cacao sur la réactivité vasculaire périphérique chez des patients atteints de diabète de type 2

Le diabète de type 2 représente 90 à 95 % de tous les cas de diabète et se caractérise par un dysfonctionnement des cellules β et une résistance à l'insuline qui provoquent l’hyperglycémie. L'hyperglycémie augmente le stress oxydatif, l'inflammation et l'activité orthosympathique et limite la biodisponibilité du monoxyde d’azote, lesquels favorisent les complications micro- (néphropathie, neuropathie, rétinopathie) et macrovasculaires (maladies cérébrovasculaires, cardiovasculaires et des artères périphériques). Ces complications sont des facteurs majeurs de morbidité et de mortalité, diminuent la qualité de vie et augmentent la charge économique liée à la santé. L'augmentation de l'activité physique et une alimentation plus équilibrée et saine constituent les soins primaires. Aux vues de leurs propriétés vasculaires prometteuses, l’intérêt pour les nutraceutiques, tels que les flavonoïdes et plus particulièrement les flavanols, s'est accru.Les flavanols sont des substances naturelles, présentes dans plusieurs fruits, thés, vins rouges, haricots et principalement dans le cacao, qui auraient des effets bénéfiques sur la santé humaine. Sur la base d'études épidémiologiques, in vitro, animales et humaines, les flavanols du cacao auraient des propriétés antioxydantes, amélioreraient la fonction endothéliale, abaisseraient la tension artérielle et réduiraient l'inflammation. Les mécanismes d'action des flavanols du cacao ne sont pas encore complètement élucidés, mais on pense que l'augmentation de la biodisponibilité et de l'activité du monoxyde d’azote et des actions antioxydantes tels que l'inhibition de la peroxydation lipidique et de la nicotinamide adénine dinucléotide phosphate oxydase ainsi que la neutralisation des radicaux libres jouent un rôle clé.Jusqu'à présent, la recherche concernant les effets vasculaires des flavanols du cacao chez les patients diabétiques est limitée et donne des résultats contradictoires. Cependant, sur la base de la physiopathologie des complications vasculaires diabétiques et des mécanismes d'action suspectés des flavanols du cacao, on pourrait supposer que les flavanols du cacao offrent une protection vasculaire aux personnes avec un diabète de type 2. Dans ce contexte, notre objectif était d’évaluer les bénéfices vasculaires pour les personnes diabétiques de type 2, en articulant le projet en trois étapes (1) examen des preuves des effets bénéfiques vasculaires des flavanols de cacao chez des patients diabétiques dans la littérature, (2) création d'un protocole de recherche robuste, standardisé et clairement décrit (étude randomisée, en double aveugle, contrôlée par placébo), et (3) mise en oeuvre de ce protocole sur les effets d’une prise unique de flavanols de cacao sur la réactivité vasculaire périphérique chez des patients diabétiques de type 2 [...]Type 2 diabetes mellitus (T2DM) represents 90 – 95 % of all diabetes cases and is characterized by β-cell dysfunction and insulin resistance leading to hyperglycemia. Hyperglycemia increases oxidative stress, inflammation, and orthosympatic activity and limits bioavailability of nitric oxide (NO), resulting in micro- (nephropathy, neuropathy, retinopathy) and macrovascular (cerebrovascular, cardiovascular, and peripheral artery disease) complications. These complications result in higher morbidity and mortality rates, decrease quality of life, and increase health economic burden. Increasing physical activity and a more balanced, healthy food intake are the first-line management. Herein, the promising vascular health benefits of nutraceuticals, like flavonoids and more specifically flavanols, have gained interest.Flavanols are natural substances present in several fruits, teas, red wines, beans, and predominantly in cocoa and are believed to beneficially affect human health. Based on epidemiological, in vitro-, animal-, and human studies, cocoa flavanols (CF) would have antioxidant properties, improve endothelial function, lower blood pressure (BP), and reduce inflammation. The mechanisms of action of CF are not yet completely understood, but it is believed that increasing NO bioavailability and –activity and antioxidative actions like inhibiting lipid peroxidation and nicotinamide adenine dinucleotide phosphate oxidase and scavenging free radicals play a key role.So far, research into the potential beneficial vascular health properties of CF in patients with diabetes mellitus (DM) is limited and demonstrated inconsistent results. However, based on the pathophysiology of diabetic vascular complications and the believed mechanisms of action of CF, one could assume that CF would exert vascular protection in T2DM subjects. Therefore, this doctoral research investigated whether CF exert vascular health benefits in patients with T2DM through the following 3 aims: (1) examine the evidence for CF-induced vascular health properties in patients with DM, (2) setup of a robust, standardized, clearly described trial protocol, and (3) investigate the acute effects of CF on peripheral vascular reactivity in patients with T2DM via execution of the described acute, randomized, double-blinded, placebo-controlled cross-over trial.First, we published a systematic review and meta-analysis on the vascular health effects of CF in patients with DM. We highlighted the need for more, robust, standardized research because of the high heterogeneity in administered intervention (dose, duration and frequency, nature of intervention), the studied population (age, sex, BMI, medical therapy, stage of disease), and measurement methods. Because of paucity of reports, we could only perform the meta-analysis on the mid/long-term effects of CF on blood pressure (BP) in patients with DM and mixed populations with increased cardiovascular risk. This meta-analysis indicated weak evidence for a reduction in diastolic BP (DBP) of, at best, 1 – 2 mmHg. No effect on systolic BP (SBP) was detected. Furthermore, CF effects on BP would be stronger in female, hypertensive, younger adults, providing a CF dose comprising at least 90 mg epicatechine (EC), and when ingested in 1 daily batch.Second, the protocol paper illustrating our setup acute, randomized, double-blinded, placebo-controlled cross-over trial was published. Here we thoroughly described our protocol trial in which we take into account the limitations in previous studies. We believe that acute studies in which subjects ingest a pure cocoa extract are the first step to gain insight in CF actions as possible confounding impact of additional fat, sugars, milk or other substances could mask/ counteract/ strengthen the effects of CF [...

Acute effects of cocoa flavanols on peripheral vascular reactivity in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) represents 90 – 95 % of all diabetes cases and is characterized by β-cell dysfunction and insulin resistance leading to hyperglycemia. Hyperglycemia increases oxidative stress, inflammation, and orthosympatic activity and limits bioavailability of nitric oxide (NO), resulting in micro- (nephropathy, neuropathy, retinopathy) and macrovascular (cerebrovascular, cardiovascular, and peripheral artery disease) complications. These complications result in higher morbidity and mortality rates, decrease quality of life, and increase health economic burden. Increasing physical activity and a more balanced, healthy food intake are the first-line management. Herein, the promising vascular health benefits of nutraceuticals, like flavonoids and more specifically flavanols, have gained interest.Flavanols are natural substances present in several fruits, teas, red wines, beans, and predominantly in cocoa and are believed to beneficially affect human health. Based on epidemiological, in vitro-, animal-, and human studies, cocoa flavanols (CF) would have antioxidant properties, improve endothelial function, lower blood pressure (BP), and reduce inflammation. The mechanisms of action of CF are not yet completely understood, but it is believed that increasing NO bioavailability and –activity and antioxidative actions like inhibiting lipid peroxidation and nicotinamide adenine dinucleotide phosphate oxidase and scavenging free radicals play a key role.So far, research into the potential beneficial vascular health properties of CF in patients with diabetes mellitus (DM) is limited and demonstrated inconsistent results. However, based on the pathophysiology of diabetic vascular complications and the believed mechanisms of action of CF, one could assume that CF would exert vascular protection in T2DM subjects. Therefore, this doctoral research investigated whether CF exert vascular health benefits in patients with T2DM through the following 3 aims: (1) examine the evidence for CF-induced vascular health properties in patients with DM, (2) setup of a robust, standardized, clearly described trial protocol, and (3) investigate the acute effects of CF on peripheral vascular reactivity in patients with T2DM via execution of the described acute, randomized, double-blinded, placebo-controlled cross-over trial.First, we published a systematic review and meta-analysis on the vascular health effects of CF in patients with DM. We highlighted the need for more, robust, standardized research because of the high heterogeneity in administered intervention (dose, duration and frequency, nature of intervention), the studied population (age, sex, BMI, medical therapy, stage of disease), and measurement methods. Because of paucity of reports, we could only perform the meta-analysis on the mid/long-term effects of CF on blood pressure (BP) in patients with DM and mixed populations with increased cardiovascular risk. This meta-analysis indicated weak evidence for a reduction in diastolic BP (DBP) of, at best, 1 – 2 mmHg. No effect on systolic BP (SBP) was detected. Furthermore, CF effects on BP would be stronger in female, hypertensive, younger adults, providing a CF dose comprising at least 90 mg epicatechine (EC), and when ingested in 1 daily batch.Second, the protocol paper illustrating our setup acute, randomized, double-blinded, placebo-controlled cross-over trial was published. Here we thoroughly described our protocol trial in which we take into account the limitations in previous studies. We believe that acute studies in which subjects ingest a pure cocoa extract are the first step to gain insight in CF actions as possible confounding impact of additional fat, sugars, milk or other substances could mask/ counteract/ strengthen the effects of CF [...]Le diabète de type 2 représente 90 à 95 % de tous les cas de diabète et se caractérise par un dysfonctionnement des cellules β et une résistance à l'insuline qui provoquent l’hyperglycémie. L'hyperglycémie augmente le stress oxydatif, l'inflammation et l'activité orthosympathique et limite la biodisponibilité du monoxyde d’azote, lesquels favorisent les complications micro- (néphropathie, neuropathie, rétinopathie) et macrovasculaires (maladies cérébrovasculaires, cardiovasculaires et des artères périphériques). Ces complications sont des facteurs majeurs de morbidité et de mortalité, diminuent la qualité de vie et augmentent la charge économique liée à la santé. L'augmentation de l'activité physique et une alimentation plus équilibrée et saine constituent les soins primaires. Aux vues de leurs propriétés vasculaires prometteuses, l’intérêt pour les nutraceutiques, tels que les flavonoïdes et plus particulièrement les flavanols, s'est accru.Les flavanols sont des substances naturelles, présentes dans plusieurs fruits, thés, vins rouges, haricots et principalement dans le cacao, qui auraient des effets bénéfiques sur la santé humaine. Sur la base d'études épidémiologiques, in vitro, animales et humaines, les flavanols du cacao auraient des propriétés antioxydantes, amélioreraient la fonction endothéliale, abaisseraient la tension artérielle et réduiraient l'inflammation. Les mécanismes d'action des flavanols du cacao ne sont pas encore complètement élucidés, mais on pense que l'augmentation de la biodisponibilité et de l'activité du monoxyde d’azote et des actions antioxydantes tels que l'inhibition de la peroxydation lipidique et de la nicotinamide adénine dinucléotide phosphate oxydase ainsi que la neutralisation des radicaux libres jouent un rôle clé.Jusqu'à présent, la recherche concernant les effets vasculaires des flavanols du cacao chez les patients diabétiques est limitée et donne des résultats contradictoires. Cependant, sur la base de la physiopathologie des complications vasculaires diabétiques et des mécanismes d'action suspectés des flavanols du cacao, on pourrait supposer que les flavanols du cacao offrent une protection vasculaire aux personnes avec un diabète de type 2. Dans ce contexte, notre objectif était d’évaluer les bénéfices vasculaires pour les personnes diabétiques de type 2, en articulant le projet en trois étapes (1) examen des preuves des effets bénéfiques vasculaires des flavanols de cacao chez des patients diabétiques dans la littérature, (2) création d'un protocole de recherche robuste, standardisé et clairement décrit (étude randomisée, en double aveugle, contrôlée par placébo), et (3) mise en oeuvre de ce protocole sur les effets d’une prise unique de flavanols de cacao sur la réactivité vasculaire périphérique chez des patients diabétiques de type 2 [...

Acute effects of cocoa flavanols on peripheral vascular reactivity in patients with type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) represents 90 – 95 % of all diabetes cases and is characterized by β-cell dysfunction and insulin resistance leading to hyperglycemia. Hyperglycemia increases oxidative stress, inflammation, and orthosympatic activity and limits bioavailability of nitric oxide (NO), resulting in micro- (nephropathy, neuropathy, retinopathy) and macrovascular (cerebrovascular, cardiovascular, and peripheral artery disease) complications. These complications result in higher morbidity and mortality rates, decrease quality of life, and increase health economic burden. Increasing physical activity and a more balanced, healthy food intake are the first-line management. Herein, the promising vascular health benefits of nutraceuticals, like flavonoids and more specifically flavanols, have gained interest.Flavanols are natural substances present in several fruits, teas, red wines, beans, and predominantly in cocoa and are believed to beneficially affect human health. Based on epidemiological, in vitro-, animal-, and human studies, cocoa flavanols (CF) would have antioxidant properties, improve endothelial function, lower blood pressure (BP), and reduce inflammation. The mechanisms of action of CF are not yet completely understood, but it is believed that increasing NO bioavailability and –activity and antioxidative actions like inhibiting lipid peroxidation and nicotinamide adenine dinucleotide phosphate oxidase and scavenging free radicals play a key role.So far, research into the potential beneficial vascular health properties of CF in patients with diabetes mellitus (DM) is limited and demonstrated inconsistent results. However, based on the pathophysiology of diabetic vascular complications and the believed mechanisms of action of CF, one could assume that CF would exert vascular protection in T2DM subjects. Therefore, this doctoral research investigated whether CF exert vascular health benefits in patients with T2DM through the following 3 aims: (1) examine the evidence for CF-induced vascular health properties in patients with DM, (2) setup of a robust, standardized, clearly described trial protocol, and (3) investigate the acute effects of CF on peripheral vascular reactivity in patients with T2DM via execution of the described acute, randomized, double-blinded, placebo-controlled cross-over trial.First, we published a systematic review and meta-analysis on the vascular health effects of CF in patients with DM. We highlighted the need for more, robust, standardized research because of the high heterogeneity in administered intervention (dose, duration and frequency, nature of intervention), the studied population (age, sex, BMI, medical therapy, stage of disease), and measurement methods. Because of paucity of reports, we could only perform the meta-analysis on the mid/long-term effects of CF on blood pressure (BP) in patients with DM and mixed populations with increased cardiovascular risk. This meta-analysis indicated weak evidence for a reduction in diastolic BP (DBP) of, at best, 1 – 2 mmHg. No effect on systolic BP (SBP) was detected. Furthermore, CF effects on BP would be stronger in female, hypertensive, younger adults, providing a CF dose comprising at least 90 mg epicatechine (EC), and when ingested in 1 daily batch.Second, the protocol paper illustrating our setup acute, randomized, double-blinded, placebo-controlled cross-over trial was published. Here we thoroughly described our protocol trial in which we take into account the limitations in previous studies. We believe that acute studies in which subjects ingest a pure cocoa extract are the first step to gain insight in CF actions as possible confounding impact of additional fat, sugars, milk or other substances could mask/ counteract/ strengthen the effects of CF [...]Le diabète de type 2 représente 90 à 95 % de tous les cas de diabète et se caractérise par un dysfonctionnement des cellules β et une résistance à l'insuline qui provoquent l’hyperglycémie. L'hyperglycémie augmente le stress oxydatif, l'inflammation et l'activité orthosympathique et limite la biodisponibilité du monoxyde d’azote, lesquels favorisent les complications micro- (néphropathie, neuropathie, rétinopathie) et macrovasculaires (maladies cérébrovasculaires, cardiovasculaires et des artères périphériques). Ces complications sont des facteurs majeurs de morbidité et de mortalité, diminuent la qualité de vie et augmentent la charge économique liée à la santé. L'augmentation de l'activité physique et une alimentation plus équilibrée et saine constituent les soins primaires. Aux vues de leurs propriétés vasculaires prometteuses, l’intérêt pour les nutraceutiques, tels que les flavonoïdes et plus particulièrement les flavanols, s'est accru.Les flavanols sont des substances naturelles, présentes dans plusieurs fruits, thés, vins rouges, haricots et principalement dans le cacao, qui auraient des effets bénéfiques sur la santé humaine. Sur la base d'études épidémiologiques, in vitro, animales et humaines, les flavanols du cacao auraient des propriétés antioxydantes, amélioreraient la fonction endothéliale, abaisseraient la tension artérielle et réduiraient l'inflammation. Les mécanismes d'action des flavanols du cacao ne sont pas encore complètement élucidés, mais on pense que l'augmentation de la biodisponibilité et de l'activité du monoxyde d’azote et des actions antioxydantes tels que l'inhibition de la peroxydation lipidique et de la nicotinamide adénine dinucléotide phosphate oxydase ainsi que la neutralisation des radicaux libres jouent un rôle clé.Jusqu'à présent, la recherche concernant les effets vasculaires des flavanols du cacao chez les patients diabétiques est limitée et donne des résultats contradictoires. Cependant, sur la base de la physiopathologie des complications vasculaires diabétiques et des mécanismes d'action suspectés des flavanols du cacao, on pourrait supposer que les flavanols du cacao offrent une protection vasculaire aux personnes avec un diabète de type 2. Dans ce contexte, notre objectif était d’évaluer les bénéfices vasculaires pour les personnes diabétiques de type 2, en articulant le projet en trois étapes (1) examen des preuves des effets bénéfiques vasculaires des flavanols de cacao chez des patients diabétiques dans la littérature, (2) création d'un protocole de recherche robuste, standardisé et clairement décrit (étude randomisée, en double aveugle, contrôlée par placébo), et (3) mise en oeuvre de ce protocole sur les effets d’une prise unique de flavanols de cacao sur la réactivité vasculaire périphérique chez des patients diabétiques de type 2 [...

Effects of a single dose of cocoa flavanols on blood pressure in patients with type 2 diabetes compared to non-diabetic people

International audienc

Move, sit, sleep, repeat: 24-hour movement behaviors among adults with type 2 diabetes mellitus

SIG - Primary Choice: M. Disease prevention and management Age Category: Older adults 65+ yrs Subject Category: Physical activity and sedentary behavior Purpose: A healthy lifestyle is associated with beneficial health effects in managing type 2 diabetes mellitus (T2DM). Important lifestyle behaviors, i.e. sleep, sedentary behavior (SB), and physical activity (PA), impact T2DM disease-specific characteristics. These behaviors are often investigated separately. A recent shift in research emphasizes the importance of considering these behaviors as part of a 24-hour day. Therefore, the aim of this study is to explore these 24-hour movement behaviors (24h-MBs) in T2DM adults. Methods: This study currently includes data of 10 T2DM adults (mean age: 66.9y, 60% men; mean years T2DM: 9.2y) and 23 adults with normal glucose levels(NGL) (mean age: 59.35y, 40% men). Participants’ 24h-MBs were measured by actigraphy (Actigraph wGT3X+). All 24h-MBs were analyzed between adults with T2DM and NGL on an average day and on weekdays and weekend days separately. Independent Sample Ttests, Mann-Whitney U Tests, and One Sample T-tests were conducted. Results: Means for 24h-MBs on an average day in T2DM adults were 635.26 (±76.61) min/SB; 275.7 (±63.05) minutes of light PA (min/LPA); 9.51 (±9.24) minutes of moderate to vigorous PA (min/MVPA); 6475.76 (±2366.39) step counts; 96.87% (±0.97) sleep efficiency; 478.29 (±26.21) minutes Total Sleep Time (min/TST); 12.55 (±4.29) minutes Wake After Sleep Onset (min/WASO). Means for the NGL adults were 586.55 (±68.54); 314.48 (±70.49); 18.41 (±13.70); 8048.16 (±2804.57); 95.70 (±2.11); 468.45 (±40.82); 18.24 (±9.04), respectively. On an average day, T2DM adults spent significantly less time in min/MVPA and min/WASO compared to NGL adults (p=0.042; p=0.023). On an average weekend day, T2DM adults spent significantly more time in min/SB and less time in min/LPA compared to NGL adults (p=0.004; p=0.009). Both groups did not meet the current 24h-MB guidelines of 150 min of MVPA/week (both p<0.001 ) and a maximum of 8 hours of SB/day (both p<0.001). Meeting the sleep guideline did not significant differ. Conclusion: These preliminary results showed high levels of min/SB and low levels of min/MVPA in both groups, which were more pronounced in the T2DM group. Recruitment is ongoing which will result in additional analyses in a larger sample. Personal, cardiometabolic and environmental correlates will be explored in the following months

Effects of a single dose of cocoa flavanols on blood pressure in patients with type 2 diabetes compared to healthy people

International audienc

Evaluation of blood pressure lowering effects of cocoa flavanols in diabetes mellitus : a systematic review and meta-analysis

In healthy people, cocoa-derived flavanols (CF) improve blood pressure (BP). This meta-analysis investigates whether CF also affect BP in diabetic patients. PubMed, Web of Science, and Embase were consulted to retrieve eligible randomized controlled trials. A random-effects model and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE)-approach were used for analyses and quality of evidence respectively. Of 267 citations, 11 trials were identified, studying either type 2 diabetic populations only (subgroup A) or type 2 diabetic patients plus non-diabetic subjects with increased cardiovascular risk (subgroup B1) or type 1 plus type 2 diabetic patients (subgroup B2). Mid/long-term CF consumption decreased BP slightly, however, only reaching statistical significance for diastolic BP in subgroup B1 (-1.89 mmHg, 95% CI: -3.24, -0.54, I2 = 55%). Considerable heterogeneity between studies and low quality of evidence caused poor quality evidence of minimal effects of CF ingestion on BP in diabetic patients

Evaluation of blood pressure lowering effects of cocoa flavanols in diabetes mellitus: A systematic review and meta-analysis

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Acute Effects of Cocoa Flavanols on Blood Pressure and Peripheral Vascular Reactivity in Type 2 Diabetes Mellitus and Essential Hypertension: A Protocol for an Acute, Randomized, Double-Blinded, Placebo-Controlled Cross-Over Trial.

International audienceIntroduction: Patients with type 2 diabetes mellitus are at high risk to develop vascular complications resulting in high morbidity and mortality. Cocoa flavanols are promising nutraceuticals with possible beneficial vascular effects in humans. However, limited research is currently available on the vascular effects in a diabetic population with inconsistent results. Possible reasons for this inconsistency might be heterogeneity in the given intervention (dose per time and day, single dose vs. split-dose, placebo formula) and the studied population (blood pressure at baseline, duration of diabetes, use of vasoactive antihypertensive and antidiabetic drugs, sex). Therefore, we aimed to develop a randomized, double-blinded, placebo-controlled cross-over trial to investigate whether cocoa flavanols have an acute impact on blood pressure and vascular reactivity in patients with type 2 diabetes with and without arterial hypertension. Methods and Analysis: We will include participants in four groups: (i) patients with type 2 diabetes without arterial hypertension, (ii) patients with type 2 diabetes with arterial hypertension and 1 antihypertensive drug, (iii) non-diabetic participants with essential hypertension and 1 antihypertensive drug, and (iv) healthy controls. All participants will complete the same protocol on both testing days, consuming high-flavanol cocoa extract (790 mg flavanols) or placebo. Macrovascular endothelial function (flow-mediated dilation) and blood pressure will be measured before and after capsule ingestion. Forearm muscle vasoreactivity (near-infrared spectroscopy) and brachial artery blood flow (echo-doppler) will be assessed in response to a dynamic handgrip exercise test after capsule ingestion. Data will be analyzed with a random intercept model in mixed models. Clinical Trial Registration: www.Clinicaltrials.gov, identifier: NCT03722199