***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 The red grape constituent resveratrol possesses cancer chemopreventive properties in rodents . The hypothesis was tested that , in healthy humans , p.o . administration of resveratrol is safe and results in measurable plasma levels of resveratrol . A phase I study of oral resveratrol ( single doses of 0.5 , 1 , 2.5 , or 5 g ) was conducted in 10 healthy volunteers per dose level .  Resveratrol and its metabolites were identified in plasma and urine by high-performance liquid chromatography-t and em mass spectrometry and quantitated by high-performance liquid chromatography-UV . Consumption of resveratrol did not cause serious adverse events . Resveratrol and six metabolites were recovered from plasma and urine . Peak plasma levels of resveratrol at the highest dose were 539 ± 384 ng/mL ( 2.4 μmol/L , mean ± SD ; n = 10 ) , which occurred 1.5 h post-dose . Peak levels of two monoglucuronides and resveratrol-3-sulfate were 3- to 8-fold higher . The area under the plasma concentration curve ( AUC ) values for resveratrol-3-sulfate and resveratrol monoglucuronides were up to 23 times greater than those of resveratrol . Urinary excretion of resveratrol and its metabolites was rapid , with 77 % of all urinary agent-derived species excreted within 4 h after the lowest dose . Cancer chemopreventive effects of resveratrol in cells in vitro require levels of at least 5 μmol/L. The results presented here intimate that consumption of high-dose resveratrol might be insufficient to elicit systemic levels commensurate with cancer chemopreventive efficacy . However , the high systemic levels of resveratrol conjugate metabolites suggest that their cancer chemopreventive properties warrant investigation . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1246–52 BACKGROUND The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables Background —The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes . We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease ( CAD ) . Methods and Results —A total of 418 subjects with type 2 diabetes were r and omly assigned to 200 mg micronized fenofibrate daily or placebo . The mean follow-up time was 39.6 months . LDL peak particle diameter ( LDL size ) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study . Progression of CAD was measured with quantitative coronary angiography . LDL size increased significantly more in the fenofibrate group than in the placebo group ( 0.98±1.04 versus 0.32±0.92 nm , P < 0.001 ) . In the combined group , small LDL size was significantly associated with progression of CAD measured as the increase of percentage diameter stenosis ( r = −0.16 , P = 0.002 ) and decreases in minimum ( r = −0.11 , P = 0.030 ) and mean ( r = −0.10 , P = 0.045 ) lumen diameter . High on-treatment LDL cholesterol , apolipoprotein B , and triglyceride concentrations were also associated with the progression of CAD . In regression analyses , small LDL size added to the effect of LDL cholesterol and apolipoprotein B on the progression of CAD . Similar associations were observed in the fenofibrate group , whereas in the placebo group , lipoprotein variables were not significantly correlated with the progression of CAD . Conclusions —Changes in LDL size and plasma lipid levels account for part of the antiatherogenic effect of fenofibrate in type 2 diabetes 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 Objective . The effect of a proprietary formulation of trans-resveratrol ( t-RSV ) on manifestations of diabetic foot syndrome ( DFS ) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers . Method . Placebo-controlled , examiner-blinded , parallel-group r and omized controlled pilot clinical trial ( ACTRN Clinical Trial Registry number 12610000629033 ) involving 24 patients with DFS ( 15 males and 9 females , average age of 56.4 ± 9.1 years ) divided into the  placebo and RSV-treatment groups was performed . 50 mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period . Results . Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo . RSV-treated patients also had a marginally improved performance in the foot pressure test . A statistically significant decline in the plasma fibrinogen level , but not CRP , was also found in the RSV-treated patients . Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment , since they have been seen on both the RSV and placebo groups , revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS . Conclusion . t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic 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 Not all patients with type 2 diabetes develop renal dysfunction . Identifying those at risk is problematic because even microalbuminuria , often used clinical ly as an indicator of future renal dysfunction , does not always precede worsening renal function . We sought to identify clinical risk factors at diagnosis of type 2 diabetes associated with later development of renal dysfunction . Of 5,102 U.K. Prospect i ve Diabetes Study ( UKPDS ) participants , prospect i ve analyses were undertaken in those without albuminuria ( n = 4,031 ) or with normal plasma creatinine ( n = 5,032 ) at diagnosis .  Stepwise proportional hazards multivariate regression was used to assess association of putative baseline risk factors with subsequent development of albuminuria ( microalbuminuria or macroalbuminuria ) or renal impairment ( Cockcroft-Gault estimated creatinine clearance < 60 ml/min or doubling of plasma creatinine ) . Over a median of 15 years of follow-up 1,544 ( 38 % ) of 4,031 patients developed albuminuria and 1,449 ( 29 % ) of 5,032 developed renal impairment . Of 4,006 patients with the requisite data for 
    Output:
    
Statistically significant ( p < 0.05 ) positive effects , indicating that resveratrol supplementation was more effective than placebo/control , were identified for systolic blood pressure , hemoglobin A1c , and creatinine , but not for fasting glucose , homeostatic model assessment of insulin resistance , diastolic blood pressure , insulin , triglycerides , LDL , or HDL cholesterol .
No major adverse events were reported and side effects of resveratrol were not different than placebo/control .
Though limitations in sample size and treatment duration preclude definitive changes in clinical practice , significant improvements in multiple cardiometabolic biomarkers and an excellent safety profile support resveratrol as a leading c and i date as an adjunct to pharmacological management of T2DM