Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats. Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial Administration of resveratrol for 5 wk has no effect on glucagon-like peptide 1 secretion, gastric emptying, or glycemic control in type 2 diabetes: a randomized controlled trial. Resveratrol supplementation decreases blood glucose without changing the circulating CD14+CD16+ monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Effects of Resveratrol on Polycystic Ovary Syndrome: A Double-blind, Randomized, Placebo-controlled Trial. Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial
OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P < 0.005 ) . Intriguingly , a correlation was found between plasma levels of a metabolite of resveratrol  ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a  resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes OBJECTIVES The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with Type 2 diabetes mellitus ( T2DM ) . BACKGROUND Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity . Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues . METHODS Ten subjects with T2DM were r and omized in a double-blind fashion to receive 3 g resveratrol or placebo daily for 12 weeks . Secondary outcomes include measures of AMPK , p-AMPK and GLUT4 expression levels , energy expenditure , physical activity levels , distribution of abdominal adipose tissue and skeletal muscle fiber type composition , body weight , HbA1c , plasma lipid subfraction , adiponectin levels , and insulin sensitivity . RESULTS There was a significant increase in both SIRT1 expression ( 2.01 vs. 0.86 arbitrary units [ AU ] , p = .016 ) and p-AMPK to AMPK expression ratio ( 2.04 vs. 0.79 AU , p = .032 ) in the resveratrol group compared with the placebo group . Although the percentage of absolute change ( 8.6 vs. -13.9 % , p = .033 ) and percentage of predicted resting metabolic rate ( RMR ; 7.8 vs. -13.9 % , p = .013 ) were increased following resveratrol , there was a significant reduction in average daily activity ( -38 vs. 43.2 % , p = .028 ) and step counts ( -39.5 vs. 11.8 % , p = .047 ) when compared with placebo . CONCLUSIONS In patients with T2DM , treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression . These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P < .05 ) , systolic blood pressure ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P < .05 ) , total cholesterol ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P < .05 ) , and total protein ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P < .05 ) in T2DM . No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes Background : Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus ( T2DM ) . We conducted a r and omized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM . We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness ( CVR ) to hypercapnia . We now report the effects of resveratrol on neurovascular coupling capacity ( CVR to cognitive stimuli ) , cognitive performance and correlations with plasma resveratrol concentrations . Methods : Thirty-six T2DM adults aged 40–80 years were r and omized to consume single doses of resveratrol ( 0 , 75 , 150 and 300 mg ) at weekly intervals . Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity ( BFV ) during a cognitive test battery . The battery consisted of dual-tasking ( finger tapping with both Trail Making task and Serial Subtraction 3 task ) and a computerized multi-tasking test that required attending to four tasks simultaneously . CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV . Results : Compared to placebo , 75 mg resveratrol significantly improved neurovascular coupling capacity , which correlated with plasma total resveratrol levels . Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol . Conclusion : a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM . Evaluation of benefits of chronic resveratrol supplementation is now warranted The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients .  In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets .  Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies . However , there are few interventional studies in human patients with atherosclerogenic diseases . The cardio-ankle vascular index ( CAVI ) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis . The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind , r and omized , placebo-controlled study , 50 patients with T2DM received supplement of a 100 mg resveratrol tablet ( total resveratrol : oligo-stilbene 27.97 mg/100 mg/day ) or placebo daily for 12 weeks . CAVI was assessed at baseline and the end of study . Body weight ( BW ) , blood pressure ( BP ) , glucose and lipid metabolic parameters , and diacron-reactive oxygen metabolites ( d-ROMs ; an oxidative stress marker ) were also measured . Resveratrol supplementation decreased systolic BP ( -5.5 ± 13.0 mmHg ) , d-ROMs ( -25.6 ± 41.8 U.CARR ) , and CAVI ( -0.4 ± 0.7 ) significantly ( P < 0.05 ) and decreased BW ( -0.8 ± 2.1 kg , P = 0.083 ) and body mass index ( -0.5 ± 0.8 kg/m2 , P = 0.092 ) slightly compared to baseline , while there were no significant changes in the placebo group . Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group . Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion , 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM . Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes . However , a large-scale cohort study is required to vali date the present findings Objective Resveratrol supplementation improves metabolic health in healthy obese men , but not in patients with type 2 diabetes ( T2D ) when given as add-on therapy . Therefore , we examined whether resveratrol can enhance metabolic health in men at risk of developing T2D . Additionally , we examined if resveratrol can stimulate brown adipose tissue ( BAT ) . Methods Thirteen male first degree relatives ( FDR ) of patients with T2D received resveratrol ( 150 mg/day ) and placebo for 30 days in a r and omized , placebo controlled , cross-over trial . Results Resveratrol significantly improved ex vivo muscle mitochondrial function on a fatty acid-derived substrate . However , resveratrol did not improve insulin sensitivity , expressed as the rate of glucose disposal during a two-step hyperinsulinemic-euglycemic clamp . Also , intrahepatic and intramyocellular lipid content , substrate utilization , energy metabolism , and cold-stimulated 18F-FDG glucose uptake in BAT ( n = 8) remained unaffected by resveratrol . In vitro experiments in adipocytes derived from human BAT confirmed the lack of effect on BAT . Conclusions Resveratrol stimulates muscle mitochondrial function in FDR males , which is in concordance with previous results . However , no other metabolic benefits of resveratrol were found in this group . This could be attributed to subject characteristics causing alterations in metabolism of resveratrol and thereby affecting resveratrol 's effectiveness . Clinical Trials.gov ID NCT02129595 The aim of this study was to investigate the impact of resveratrol supplementation along with non-surgical periodontal treatment on blood glucose , insulin , insulin resistance , triglyceride ( TG ) , and periodontal markers in patients with type 2 diabetes with periodontal disease . In this double-blind clinical trial study , 43 patients with diabetes with chronic periodontitis were participated . Subjects were r and omly allocated to intervention and control groups . The intervention and control groups received either 480 mg/day of resveratrol or placebo capsules ( two pills ) for 4 weeks . Fasting blood glucose , insulin , insulin resistance ( homeostasis model assessment of insulin resistance ) , TGs , and pocket depth were measured in all subjects ' pre-intervention and post-intervention . The mean serum levels of fasting insulin and insulin resistance ( homeostasis model assessment of insulin resistance ) were significantly lower in the intervention group compared with control group ( 10.42 ± 0.28 and 10.92 ± 0.9 ; 3.66 ± 0.97 and 4.49 ± 1.56 , respectively ) . There was a significant difference in the mean pocket depth between intervention and control groups ( 2.35 ± 0.6 and 3.38 ± 0.5 , respectively ) following intervention . No significant differences were observed in the mean levels of fasting blood glucose and TGs between two groups ' post-intervention . It is recommended that resveratrol supplementation may be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease . Copyright © 2016 John Wiley & Sons , Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol  significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol  improves insulin sensitivity in humans , which might be due to a resveratrol-induced  decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia . The aim of this study was to determine whether resveratrol , a polyphenol antioxidant compound , when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older , obese , diabetic rats . Diabetes was induced in 6-month old , obese , male Wistar rats via a single intravenous dose of streptozotocin ( 65 mg/kg ) . R and omly selected animals were administered resveratrol ( 2 mg/kg ) via oral gavage daily for 8 weeks . Body weights , blood glucose levels , food intake and water consumption were monitored , and assessment s of vascular reactivity , tactile allodynia and left ventricular function were performed . Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats ( P<0·05 ) . There were no significant changes in st and ardised vasorelaxation responses , plasma glucose concentrations , water consumption , body weight , left ventricular hypertrophy , kidney hypertrophy , heart rate or left ventricular compliance with resveratrol administration . Resveratrol-mediated improvements in vascular and nerve function in old , obese , diabetic rats were associated with its reported antioxidant effects . Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus ( i.e. hyperglycaemia , polydypsia and a failure to thrive ) . This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus Objectives Patients with type 2 diabetes ( T2DM ) are at increased fracture risk . Resveratrol has shown beneficial effects on bone health in few studies . The aim of this trial was to investigate the effects of resveratrol on bone mineral density ( BMD ) and on calcium metabolism biomarkers in T2DM patients . Methods In this double-blind r and omized placebo-controlled trial 192 T2DM out patients were r and omized to receive resveratrol 500 mg/day ( Resv500 arm ) , resveratrol 40 mg/day ( Resv40 arm ) or placebo for 6 months . BMD , bone mineral content ( BMC ) , serum calcium , phosphorus , alkaline phosphatase , and 25-hydroxy vitamin D were measured at baseline and after 6 months . Results At follow-up , calcium concentrations increased in all patients , while within-group variations in alkaline phosphatase were higher in both resveratrol arms , and 25-hydroxy vitamin D increased in the Resv500 arm only , without between-group differences . Whole-body BMD significantly decreased in the placebo group , while whole-body BMC decreased in both the placebo and Resv40 arms . No significant changes in BMD and BMC values occurred in the Resv500 arm . The adjusted mean differences of change from baseline were significantly different in the Resv500 arm vs placebo for whole-body BMD ( 0.01 vs −0.03 g/cm2 , p = 0.001 ) , whole-body BMC ( 4.04 vs −58.8 g , p < 0.001 ) , whole-body T-score ( 0.15 vs −0.26 ) , and serum phosphorus ( 0.07 vs −0.01 µmol/L , p = 0.002 ) . In subgroup analyses , in Resv500 treated- patients BMD values increased to higher levels in those with lower calcium and 25-hydroxy vitamin D values , and in alcohol drinkers . Conclusions Supplementation with 500 mg resveratrol prevented bone density loss in patients with T2DM , in particular , in those with unfavorable conditions at baseline BACKGROUND Resveratrol has been reported to lower glycemia in rodent models of type 2 diabetes associated with the stimulation of glucagon-like peptide 1 ( GLP-1 ) , which is known to slow gastric emptying , stimulate insulin secretion , and suppress glucagon secretion and energy intake . OBJECTIVE We evaluated the effects of 5 wk of resveratrol treatment on GLP-1 secretion , gastric emptying , and glycemic control in type 2 diabetes . DESIGN Fourteen patients with diet-controlled type-2 diabetes [ mean ± SEM glycated hemoglobin ( HbA1c ) : 6.4 ± 0.2 % ( 46.4 ± 2.2 mmol/mol ) ] received resveratrol ( 500 mg twice daily ) or a placebo over two 5-wk intervention periods with a 5-wk washout period in between in a double-blind , r and omized , crossover design . Before and after each intervention period ( 4 visits ) , body weight and HbA1c were measured , and patients were evaluated after an overnight fast with a st and ardized mashed-potato meal labeled with 100 μg (13)C-octanoic acid to measure blood glucose and plasma GLP-1 concentrations and gastric emptying ( breath test ) over 240 min . Daily energy intake was estimated from 3-d food diaries during the week before each visit . RESULTS Fasting and postpr and ial blood glucose and plasma total GLP-1 as well as gastric emptying were similar at each assessment , and the change in each variable from weeks 0 to 5 did not differ between resveratrol and placebo groups . Similarly , changes in HbA1c , daily energy intake , and body weight after 5 wk did not differ between the 2 treatments . CONCLUSIONS In patients with diet-controlled type 2 diabetes , 5 wk of twice-daily 500 mg-resveratrol supplementation had no effect on GLP-1 secretion , glycemic control , gastric emptying , body weight , or energy intake . Our observations do not support the use of resveratrol for improving glycemic control . This trial was registered at www.anzctr.org.au as ACTRN12613000717752 Chronic low- grade inflammation is the hallmark of type 2 diabetes ( T2D ) . Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects , clinical trials addressing these effects in patients with T2D are limited . Therefore , in the present study , we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a r and omized , double-blind , placebo-controlled clinical trial . A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks . Percentage of CD14+CD16 + monocytes , plasma levels of inflammatory cytokines ( tumor necrosis factor α , interleukin [ IL ] 1β , IL-6 , and monocyte chemoattractant protein-1 ) , the expression levels of genes involved in the inflammatory responses ( toll-like receptor 2 , toll-like receptor 4 , and nuclear factor κB ) , lipopolysaccharide-stimulated cytokine ( tumor necrosis factor α , IL-1β , and IL-6 ) secretion from peripheral blood mononuclear cells , and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study . Compared with the placebo group , we could not detect any significant difference in the percentage of CD14+CD16 + monocytes , lipopolysaccharide-induced cytokine secretion , plasma levels of inflammatory cytokines , and the expression of inflammatory genes in resveratrol group . Moreover , we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure . In conclusion , 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers CONTEXT Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy affecting women of reproductive age . Hyper and rogenism is the central feature of PCOS . Studies on isolated ovarian theca-interstitial cells suggest that resveratrol , a natural polyphenol , reduces and rogen production . OBJECTIVE This study was design ed to evaluate endocrine and metabolic effects of resveratrol on PCOS . DESIGN AND SETTING This was a r and omized ( 1:1 ) double-blind , placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital . PATIENTS AND OTHER PARTICIPANTS Subjects with PCOS were identified according to the Rotterdam criteria . Thirty-four subjects were enrolled and 30 subjects completed the trial . Evaluations were performed at baseline and repeated after 3 months of treatment . INTERVENTION Resveratrol ( 1,500 mg p.o . ) or placebo were administered daily . MAIN OUTCOME MEASURE Primary outcome was the change in the serum total T. RESULTS Resveratrol treatment led to a significant decrease of total T by 23.1 % ( P = .01 ) . In parallel , resveratrol induced a 22.2 % decrease of dehydroepi and rosterone sulfate ( P = .01 ) , a decrease of fasting insulin level by 31.8 % ( P = .007 ) and an increase of the Insulin Sensitivity Index ( Matsuda and DeFronzo ) by 66.3 % ( P = .04 ) . Levels of gonadotropins , the lipid profile as well as markers of inflammation and endothelial function were not significantly altered . CONCLUSIONS Resveratrol significantly reduced ovarian and adrenal and rogens . This effect may be , at least in part , related to an improvement of insulin sensitivity and a decline of insulin level Abstract Aims The anti-inflammatory effects of the polyphenol resveratrol in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Its role on pentraxin 3 ( PTX3 ) concentrations , a human acute phase protein , has never been evaluated . Our aim was to determine whether a two-dosage resveratrol supplementation ( 500 and 40 mg/day ) has an impact on PTX3 values in T2DM patients from a double-blind r and omized placebo-controlled trial .  Variations in total antioxidant status ( TAS ) were evaluated too . Methods A total of 192 T2DM patients were r and omized to receive resveratrol 500 mg/day ( Resv 500 arm ) , resveratrol 40 mg/day ( Resv 40 arm ) or placebo for 6 months . At baseline and at the trial end , PTX3 and TAS values were determined . Results A dose-dependent increase in PTX3 concentrations of 4.7 % ( Resv 40 arm ) and 26.3 % ( Resv 500 arm ) , and 8.0 % reduction after placebo were found . Adjusted mean differences of change versus placebo were 0.16 ( 95 % CI 0.01–0.32 ) and 0.25 ( 0.09–0.42 ) in the Resv 40 and Resv 500 arms , respectively . At subgroup analyses , lower diabetes duration , aspirin , alcohol use , younger age , female gender , smoking ( Resv 500 arm ) and female gender and aspirin use ( Resv 40 arm ) were associated with higher PTX3 increments . A dose-dependent increment in TAS values in the resveratrol arms ( 1.4 and 6.4 % for Resv 40 and Resv 500 , respectively ) , and a reduction in placebo arm ( −8.9 % ) were observed . Adjusted mean differences of change were 28.5 ( 95 % CI 10.1–46.8 ) and 44.8 ( 25.4–64.1 ) in the Resv 40 and Resv 500 arms , respectively . Conclusion Resveratrol supplementation  increased PTX3 and TAS levels in a dose-dependent manner in T2DM patients . At present , potential clinical implication s of these results remain unclear . Clinical Trials.gov IdentifierNCT02244879 Abstract Aims Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes ( T2D ) . In vitro and animal studies have shown that resveratrol exerts an antioxidant effect , but clinical trials addressing this effect in patients with T2D are limited . The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a r and omized , placebo-controlled , double-blind clinical trial . Methods A total of 48 patients with T2D r and omly were assigned to receive 800 mg/day resveratrol or placebo for 2 months . Plasma total antioxidant capacity , malondialdehyde concentration , protein carbonyl and total thiol contents , intracellular superoxide anion ( O2− · ) and hydrogen peroxide ( H2O2 ) in P BMC s , the expression of genes involved in oxidative stress responses ( Nrf2 , SOD , Cat , HO-1 , RAGE , NOS ) in P BMC s , and metabolic and anthropometric parameters were measured at the baseline and at the trial end . Results Compared with the placebo group , resveratrol reduced plasma protein carbonyl content and P BMC s O2− · level and significantly increased plasma total antioxidant capacity and total thiol content . Furthermore , the expression of Nrf2 and SOD was significantly increased after resveratrol consumption . Resveratrol had no significant effects on the metabolic and anthropometric parameters except for a significant reduction in weight , BMI , and blood pressure levels . Resveratrol was well tolerated , and no serious adverse event was occurred . Conclusions Our study demonstrated that 8 weeks of supplementation with 800 mg/day resveratrol has an antioxidant effect in the blood and P BMC s of patients with T2D . Clinical Trial Registry number and website I RCT registration number : I RCT 2015072523336N1 and http://en . search .i rct .ir/view/24752
The drug also reduced homeostasis model assessment of insulin resistance ( HOMA-IR ) index , systolic blood pressure , and diastolic blood pressure among participants with T2DM .
The changes in hemoglobin A1c ( HbA1c ) , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol were negligible .
Subgroup analysis comparing the resveratrol supplementation doses of < 100 mg/d versus ≥ 100 mg/d revealed a significant difference in fasting plasma glucose .
In particular , the latter dose presented more favorable results .
This meta- analysis provides evidence that supplementation of resveratrol may benefit management of T2DM
Although the regular consumption of resveratrol has been known to improve glucose homeostasis and reverse insulin resistance in type 2 diabetes mellitus ( T2DM ) , the reported results are inconsistent .
Thus , we aim ed to assess the effects of resveratrol on glycemic control and insulin sensitivity among patients with T2DM .