title: Does supplementation with green tea extract improve insulin resistance in obese type 2 diabetics? A randomized, double-blind, and placebo-controlled clinical trial. Cinnamon supplementation does not improve glycemic control in postmenopausal type 2 diabetes patients. Antioxidant intakes and food sources in Greek adults. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Serum fructosamine versus glycosylated hemoglobin as an index of glycemic control, hospitalization, and infection in diabetic hemodialysis patients. Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds The effect of an extract of green and black tea on glucose control in adults with type 2 diabetes mellitus: double-blind randomized study. Chronic Ingestion of Flavan-3-ols and Isoflavones Improves Insulin Sensitivity and Lipoprotein Status and Attenuates Estimated 10-Year CVD Risk in Medicated Postmenopausal Women With Type 2 Diabetes Effects of a flaxseed-derived lignan supplement on C-reactive protein, IL-6 and retinol-binding protein 4 in type 2 diabetic patients. Cinnamon extract improves fasting blood glucose and glycosylated hemoglobin level in Chinese patients with type 2 diabetes. Herbal tea in the treatment of diabetes mellitus. Effect of acacia polyphenol on glucose homeostasis in subjects with impaired glucose tolerance: A randomized multicenter feeding trial Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients Effects of a Flaxseed-Derived Lignan Supplement in Type 2 Diabetic Patients: A Randomized, Double-Blind, Cross-Over Trial Dual association between polyphenol intake and breast cancer risk according to alcohol consumption level: a prospective cohort study Association between serum fructosamine and mortality in elderly women: the study of osteoporotic fractures. A double blind randomised placebo controlled cross over study of a herbal preparation containing Salacia reticulata in the treatment of type 2 diabetes. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: the PREDIMED study. Study of curcumin and genistein interactions with human serum albumin. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian traditional medicine. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Association of Hemoglobin A1c with Cardiovascular Disease and Mortality in Adults: The European Prospective Investigation into Cancer in Norfolk Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects.
abstract: BACKGROUND Green tea is one of the most popular beverages in the world . It is believed to have beneficial effects in the prevention and treatment of many diseases , one of which is type 2 diabetes . The aim of the study is to examine the effect of a decaffeinated green tea extract ( GTE ) providing a daily dose of 856 mg of epigallocatechin gallate ( EGCG ) on obese individuals with type 2 diabetes . MATERIAL S AND METHODS The clinical trial was a r and omized , double-blind , placebo-controlled clinical trial conducted from December 2007 through November 2008 . The subjects were r and omly assigned to either receive 1,500 mg of a decaffeinated GTE or placebo daily for 16 weeks . Sixty-eight of 80 subjects , ages 20 - 65 years with BMI > 25 kg/m2 and type 2 diabetes for more than one year , completed this study .  Homeostasis model assessment for insulin resistance ( HOMA-IR ) was used as the major outcome measurement . At baseline and after 16 weeks of treatment , anthropometric measurements , fasting glucose , hemoglobin A1C percent ( HbA1C ) , hormone peptides , and plasma lipoproteins were measured from both groups . RESULTS No statistically significant differences were detected between the decaffeinated GTE and placebo groups in any measured variable . A statistically significant within-group 0.4-percent reduction in HbA1C ( from 8.4 to 8.0 % ) was observed after GTE treatment compared to baseline . Within-group comparison also revealed that the GTE group had significant reductions in waist circumference ( WC ) , HOMA-IR index , and insulin level , and a significant increase in the level of ghrelin . Within-group comparison of those in the placebo group showed a significant increase in the level of ghrelin . CONCLUSIONS This study found no statistical difference in any measured variable between the decaffeinated GTE and placebo groups ; however , there were some statistically significant within-group changes detected . More research is required to determine whether a decaffeinated GTE st and ardized for EGCG content will provide any clinical benefits in obese individuals with type 2 diabetes . Clinical Trial Registration NO : NCT00567905 In vitro and in vivo animal studies have reported strong insulin-like or insulin-potentiating effects after cinnamon administration . Recently , a human intervention study showed that cinnamon supplementation ( 1 g/d ) strongly reduced fasting blood glucose concentration ( 30 % ) and improved the blood lipid profile in patients with type 2 diabetes . The objective of this study was to investigate the effects of cinnamon supplementation on insulin sensitivity and /or glucose tolerance and blood lipid profile in patients with type 2 diabetes . Therefore , a total of 25 postmenopausal patients with type 2 diabetes ( aged 62.9 + /- 1.5 y , BMI 30.4 + /- 0.9 kg/m2 ) participated in a 6-wk intervention during which they were supplemented with either cinnamon ( Cinnamomum cassia , 1.5 g/d ) or a placebo . Before and after 2 and 6 wk of supplementation , arterialized blood sample s were obtained and oral glucose tolerance tests were performed . Blood lipid profiles and multiple indices of whole-body insulin sensitivity were determined . There were no time x treatment interactions for whole-body insulin sensitivity or oral glucose tolerance . The blood lipid profile of fasting subjects did not change after cinnamon supplementation . We conclude that cinnamon supplementation ( 1.5 g/d ) does not improve whole-body insulin sensitivity or oral glucose tolerance and does not modulate blood lipid profile in postmenopausal patients with type 2 diabetes . More research on the proposed health benefits of cinnamon supplementation is warranted before health cl aims should be made Antioxidants are compounds physiologically produced or provided through the diet with a potential to inhibit the oxidation of important biological molecules , such as proteins , lipids , and DNA . The contemporary Greek diet is still strongly influenced by Mediterranean dietary traditions . The traditional Mediterranean diet ( MD ) is a plant-based diet with apparently beneficial health properties , to which a high antioxidant content may contribute . To explore this issue in detail , a data base of the content of > 200  Greek foods and recipes for a wide spectrum of antioxidant compounds and indices ( flavonoids , proanthocyannidins , other antioxidant microcomponents , and total antioxidant capacity ) was developed . The data base enabled the estimation of antioxidant intakes in Greece using the population -based European Prospect i ve Investigation into Cancer and Nutrition study , in which > 28,000 Greeks participate . The results of this work suggest that the contemporary MD in the Greek population is a rich source of a variety of antioxidants . These data can be used in studies about the relationship between antioxidant intake and chronic diseases in the Greek population 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 Diabetes is the most common cause of end-stage renal disease and an important risk factor for morbidity and mortality in dialysis patients . Glycemic control , utilizing serial measurement of glycosylated hemoglobin ( HbA1c ) , is generally recommended to limit end-organ damage , including cardiovascular morbidity and mortality . We , along with others , have previously suggested that HbA1c may not be a reliable measure of glycemic control in dialysis patients , and have therefore explored the use of serum fructosamine ( SF ) as an alternative marker . The objective of this study was to compare HbA1c levels with SF in monitoring glycemic control and associated morbidity ( infection and hospitalization ) in diabetic patients in a large urban hemodialysis ( HD ) center . We enrolled 100 diabetic HD patients and followed them up prospect ively for 3 years . Data on demographics , as well as biochemical and clinical data , including hospitalizations and infections , were recorded . The mean age was 63 years . In all 54 % were women and the majority were African Americans ( 72 % ) . As expected , HbA1c and albumin-corrected fructosamine ( AlbF ) levels were highly correlated and both were significantly associated with serum glucose . AlbF , however , was more highly correlated with mean glucose values when less than 150 mg/dl and was a more useful predictor of morbidity . By univariate logistic regression and by Poisson regression analysis , AlbF , but not HbA1c , was a significant predictor of hospitalization . Additionally , in patients dialyzed by arteriovenous ( AV ) access ( that is , excluding those dialyzed via vascular catheters ) , AlbF , but not HbA1c , was a significant predictor of infection . In conclusion , AlbF is as reliable a marker as HbA1c for glycemic control in diabetic patients on HD , and may be advantageous for patients with serum glucose in a desirable therapeutic range ( < 150 mg/dl ) . In addition , AlbF , but not HbA1c , is associated with morbidity ( hospitalizations and infections ) in diabetic patients on HD Aims /hypothesisThere is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes . Here , we investigate the relationship between HbA1c and the risks of vascular complications and death in such patients . Methods Eleven thous and one hundred and forty patients were r and omised to intensive or st and ard glucose control in the Action in Diabetes and Vascular disease : Preterax and Diamicron Modified Release Controlled Evaluation ( ADVANCE ) trial . Glycaemic exposure was assessed as the mean of HbA1c measurements during follow-up and prior to the first event . Adjusted risks for each HbA1c decile were estimated using Cox models . Possible differences in the association between HbA1c and risks at different levels of HbA1c were explored using linear spline models . Results There was a non-linear relationship between mean HbA1c during follow-up and the risks of macrovascular events , microvascular events and death . Within the range of HbA1c studied ( 5.5–10.5 % ) , there was evidence of ‘ thresholds ’ , such that below HbA1c levels of 7.0 % for macrovascular events and death , and 6.5 % for microvascular events , there was no significant change in risks ( all p > 0.8 ) . Above these thresholds , the risks increased significantly : every 1 % higher HbA1c level was associated with a 38 % higher risk of a macrovascular event , a 40 % higher risk of a microvascular event and a 38 % higher risk of death ( all p < 0.0001 ) . Conclusions /interpretationIn patients with type 2 diabetes , HbA1c levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0 % and microvascular events down to a threshold of 6.5 % . There was no evidence of lower risks below these levels but neither was there clear evidence of harm . Trial Registration : Clinical Trial.gov NCT00145925 Funding : Servier and the National Health and Medical Research Council of Australia ( project grant ID 211086 and programme grant IDs 358395 and 571281 Recent evidence suggests that tea from Camellia sinensis ( eg , green , oolong , and black tea ) may have a hypoglycemic effect . We evaluated the ability of an extract of green and black tea to improve glucose control over a 3-month period . A double-blind , placebo-controlled , r and omized multiple-dose ( 0 , 375 , or 750 mg per day for 3 months ) study in adults with type 2 diabetes mellitus not taking insulin was performed . The primary end point was change in glycosylated hemoglobin at 3 months . The 49 subjects who completed this study were predominantly white with an average age of 65 years and a median duration of diabetes of 6 years , and 80 % of them reported using hypoglycemic medication .  After 3 months , the mean changes in glycosylated hemoglobin were + 0.4 ( 95 % confidence interval , 0.2 - 0.6 ) , + 0.3 ( 0.1 - 0.5 ) , and + 0.5 ( 0.1 - 0.9 ) in the placebo , 375-mg , and 750-mg arms , respectively . The changes were not significantly different between study arms . We did not find a hypoglycemic effect of extract of green and black tea in adults with type 2 diabetes mellitus OBJECTIVE 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 . RESEARCH DESIGN AND METHODS 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 r and omized 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 . RESULTS 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 result ed 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 Prospect i ve 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 , HbA1c , or glucose was observed . CONCLUSIONS One-year intervention with flavan-3-ols and isoflavones improved biomarkers of CVD risk , highlighting the additional benefit of flavonoids to st and ard drug therapy in managing CVD risk in postmenopausal type 2 diabetic patients Elevated C-reactive protein ( CRP ) , IL-6 and retinol-binding protein 4 ( RBP4 ) levels are associated with insulin resistance and diabetes mellitus . Phytoestrogens ( including lignans and isoflavones ) may enhance the management of diabetes and are hypothesized to act through inflammation pathways . The present study explored the effects of flaxseed-derived lignan on inflammatory factors and RBP4 concentrations in type 2 diabetics , who have higher levels of these biomarkers . Seventy community-dwelling diabetic patients ( twenty-six men and forty-four post-menopausal women ) with mild hypercholesterolaemia completed a r and omized , double-blind , placebo-controlled , cross-over trial of supplementation with flaxseed-derived lignan capsules ( 360 mg/d ) or placebo for 12 weeks , separated by an 8-week wash-out period . The participants maintained their habitual diets and levels of physical activity . Baseline to follow-up concentrations of CRP increased significantly within the placebo group ( 1.42 ( sem 0.19 ) v. 1.96 ( sem 0.22 ) mg/l , P < 0.001 ) , but were comparatively unchanged in the lignan-supplemented group ( 1.67 ( sem 0.19 ) v. 1.90 ( sem 0.26 ) mg/l , P = 0.94 ) ; a significant difference was observed between treatments ( - 0.45 ( 95 % CI - 0.76 , - 0.08 ) mg/l , P = 0.021 ) . This effect was confined to women ( P = 0.016 ) , but not observed in men ( P = 0.49 ) . No between-treatment differences were found with regard to IL-6 or RBP4 ; though IL-6 concentrations increased significantly from baseline to follow-up in both groups ( P = 0.004 and P < 0.001 following lignan and placebo treatments , respectively ) . The study suggests that lignan might modulate CRP levels in type 2 diabetics . These results need to be confirmed by further large clinical trials of longer duration For thous and s of years , cinnamon has been used as a traditional treatment in China . However , there are no studies to date that investigate whether cinnamon supplements are able to aid in the treatment of type 2 diabetes in Chinese subjects . We hypothesized cinnamon should be effective in improving blood glucose control in Chinese patients with type 2 diabetes . To address this hypothesis , we performed a r and omized , double-blinded clinical study to analyze the effect of cinnamon extract on glycosylated hemoglobin A(1c ) and fasting blood glucose levels in Chinese patients with type 2 diabetes . A total of 66 patients with type 2 diabetes were recruited and r and omly divided into 3 groups : placebo and low-dose and high-dose supplementation with cinnamon extract at 120 and 360 mg/d , respectively . Patients in all 3 groups took gliclazide during the entire 3 months of the study . Both hemoglobin A(1c ) and fasting blood glucose levels were significantly reduced in patients in the low- and high-dose groups , whereas they were not changed in the placebo group . The blood triglyceride levels were also significantly reduced in the low-dose group . The blood levels of total cholesterol , high-density lipoprotein cholesterol , low-density lipoprotein cholesterol , and liver transaminase remained unchanged in the 3 groups . In conclusion , our study indicates that cinnamon supplementation is able to significantly improve blood glucose control in Chinese patients with type 2 diabetes OBJECTIVE To evaluate the effects of a native herbal tea in patients with type 2 diabetes . DESIGN R and omized , placebo-controlled , single-blind study . SETTING The Metabolic Centre at the University of Alberta Hospitals . SUBJECTS Forty volunteers with type 2 diabetes . INTERVENTIONS After a 1 month " run-in " period , subjects drank 250 mL/d of either the herbal tea or a placebo tea for 10 days , and were followed up for a further 4 weeks . OUTCOME MEASURES A responder analysis defined as a 10 % change in mean blood glucose levels based on 4 capillary glucose readings daily . Secondary end points included changes in HbA1c , fructosamine and response to a meal challenge using Ensure . RESULTS The responder analysis showed no benefit from the herbal tea .  Fructosamine levels before and after tea therapy decreased significantly in both study groups . Mean HbA1c levels and incremental areas under the glucose curve ( AUC ) in the meal challenge did not change in either study group . These data were reanalysed in hyperglycemic subjects with HbA1c levels greater than 120 % of normal . The responder analysis and HbA1c levels did not change in either group . Mean ( and st and ard deviation ) fructosamine levels , before and after tea therapy , were significantly lower in the herbal tea group than in the placebo tea group ( 361 [ 98 ] versus 338 [ 100 ] micromol/L , p < 0.01 compared with 338 [ 60 ] versus 323 [ 49 ] micromol/L , p = 0.08 ) . In the hyperglycemic subgroup the mean AUC during the meal challenge , before versus after tea therapy , was 776 ( 369 ) versus 639 ( 331 ) mmol/L ( p = 0.22 ) in the herbal tea group and 433 ( 125 ) versus 420 ( 173 ) mmol/L ( p = 0.90 ) in the placebo group . CONCLUSIONS Although the responder analysis failed to show an effect of the herbal tea , the data suggest there may be a short-term benefit from the tea in subjects with poor glycemic control Numerous in vitro and animal studies , as well as clinical trials have indicated that plant-derived polyphenols exert beneficial effects on glucose intolerance or type 2 diabetes .  This clinical study aim ed to investigate the effects of acacia polyphenol ( AP ) on glucose and insulin responses to an oral glucose tolerance test ( OGTT ) in non-diabetic subjects with impaired glucose tolerance ( IGT ) . A r and omized , double-blind , placebo-controlled trial was conducted in a total of 34 enrolled subjects . The subjects were r and omly assigned to the AP-containing dietary supplement ( AP supplement ; in a daily dose of 250 mg as AP ; n=17 ) or placebo ( n=17 ) and the intervention was continued for 8 weeks . Prior to the start of the intervention ( baseline ) and after 4 and 8 weeks of intervention , plasma glucose and insulin were measured during a two-hour OGTT . Compared with the baseline , plasma glucose and insulin levels at 90 and /or 120 min , as well as the total area under the curve values during the OGTT ( AUC0→2h ) for glucose and insulin , were significantly reduced in the AP group , but not in the placebo group after intervention for 8 weeks . The decline from baseline in plasma glucose and insulin at 90 or 120 min of the OGTT for the AP group was significantly greater compared with that of the placebo group after 8 weeks of intervention . No AP supplement-related adverse side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the study period . The AP supplement may have the potential to improve glucose homeostasis in subjects with IGT 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 Background Flaxseed consumption has been shown to improve blood lipids in humans and flaxseed-derived lignan has been shown to enhance glycemic control in animals . The study aim ed to investigate the effect of a flaxseed-derived lignan supplement on glycemic control , lipid profiles and insulin sensitivity in type 2 diabetic patients . Methodology /Principal Findings This was a r and omized , double-blind , placebo-controlled , cross-over trial and it was conducted between April and December 2006 in Shanghai , China . Seventy-three type 2 diabetic patients with mild hypercholesterolemia were enrolled into the study . Patients were r and omized to supplementation with flaxseed-derived lignan capsules ( 360 mg lignan per day ) or placebo for 12 weeks , separated by an 8-week wash-out period . HbA1c , lipid profiles , insulin resistance index and inflammatory factors were measured . Sixty-eight completed the study and were included in the analyses . The lignan supplement significantly improved glycemic control as measured by HbA1c ( -0.10±0.65 % vs. 0.09±0.52 % , P = 0.001 ) compared to placebo ; however , no significant changes were observed in fasting glucose and insulin concentrations , insulin resistance and blood lipid profiles . Urinary excretion of lignan metabolites ( enterodiol and enterolactone ) was significantly higher after the lignan supplement intervention compared to baseline ( 14.2±18.1 vs. 1.2±2.4 µg/mL , P<0.001 ) . Data also suggested minimal competition between lignan and isoflavones for bioavailability when measured by the excretion concentrations . Conclusions / Significance Daily lignan supplementation result ed in modest , yet statistically significant improvements in glycemic control in type 2 diabetic patients without apparently affecting fasting glucose , lipid profiles and insulin sensitivity . Further studies are needed to vali date these findings and explore the efficacy of lignans on type 2 diabetes . Trial Registration Clinical Trials.gov Studies of the association between polyphenols dietary intake and  breast cancer risk have been limited due to the lack of detailed food composition tables . In addition , none has examined this association according to alcohol intake , despite the facts that alcohol is an established risk factor for breast cancer and that the contribution of alcoholic beverages to polyphenol intake varies according to the level of alcohol consumption . Our objectives were ( 1 ) to estimate the associations between breast cancer risk and a wide range of dietary polyphenols using the recently published Phenol-Explorer data base ; and ( 2 ) to evaluate if/how alcohol intake modulates these relationships . 4,141 women from the SU.VI.MAX prospect i ve cohort were followed from 1994 to 2007 ( median followup : 12.6 years ) ; 152 developed a first incident invasive primary breast cancer .  Dietary intakes  were assessed by repeated 24-h records . The Phenol-Explorer data base was used to estimate polyphenol intake . Multivariable Cox proportional hazards models were used to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) for quartiles of polyphenol intake . Analyses were stratified by median alcohol intake ( < vs. ≥6.5 g/d ) . In non-to-low alcohol drinkers , intakes of some classes of polyphenols were associated with decreased breast cancer risk : hydroxybenzoic acids ( HRQ4vsQ1 = 0.38 , 95 % CI : 0.17–0.86 , Ptrend = 0.005 ) , flavonoids ( 0.35 , 0.17–0.75 , Ptrend = 0.02 ) , flavonols ( 0.36 , 0.18–0.74 , Ptrend = 0.002 ) , catechins ( 0.48 , 0.22–1.05 , Ptrend = 0.02 ) , theaflavins ( 0.42 , 0.19–0.93 , Ptrend = 0.02 ) , and proanthocyanidins ( 0.39 , 0.18–0.84 , Ptrend = 0.02 ) . In contrast , in women with higher alcohol use  , intakes of hydroxybenzoic acids ( 2.28 , 1.16–4.49 , Ptrend = 0.04 ) , flavonoids ( 2.46 , 1.23–4.92 , Ptrend = 0.01 ) , anthocyanins ( 2.94 , 1.32–6.53 , Ptrend = 0.01 ) , catechins ( 2.28 , 1.19–4.36 , Ptrend = 0.02 ) , and proanthocyanidins ( 2.98 , 1.40–6.33 , Ptrend = 0.006 ) were associated with increased breast cancer risk . In conclusion , this prospect i ve study suggests that several classes of polyphenols could potentially contribute to breast cancer prevention among non-to-low alcohol drinkers , but some may increase breast cancer risk among women with higher alcohol intake Serum fructosamine levels can be used to estimate long-term serum glucose values and can be measured in frozen serum . The authors examined whether fructosamine levels were associated with mortality in a cohort of 9,704 white women ( > or = 65 years of age ) recruited from September 1986 to October 1988 at four clinical centers in the United States . A r and om sample of women who had died during a mean of 6 years of follow-up ( n = 55 ) was compared with r and omly  selected controls  ( n = 276 , 54 of whom had died ) .  Fructosamine assays  were performed blinded to vital status . Hazard ratios with 95 % confidence intervals were adjusted for age , clinical center , smoking , hypertension , and serum albumin and cholesterol levels . Each st and ard deviation ( 46 micromol ) increase in fructosamine level was associated with a 1.3-fold ( 95 % confidence interval ( CI ) 1.0 - 1.6 , p = 0.04 ) increased rate of all-cause mortality , including a 1.5-fold ( 95 % CI 1.0 - 2.1 , p = 0.03 ) increase in cardiovascular disease mortality . Elevated fructosamine levels ( > 285 micromol/liter ) were associated with a 4.3-fold ( 95 % CI 1.6 - 12 , p = 0.004 ) increased rate of cardiovascular mortality ; in women without a history of diabetes , the hazard ratio was 4.6 ( 95 % CI 1.3 - 16 , p = 0.02 ) . Fructosamine level , or another indicator of glycemia , should be included when the risk of cardiovascular disease among older patients is evaluated We conducted a r and omised single centre double blind cross over clinical trial to investigate the effects of a herbal tea containing Salacia reticulata ( Kothala Himbutu tea ) in patients with type II diabetes mellitus . Fifty-one patients with type II diabetes mellitus for longer than 6 months and with evidence of stable glycaemic control over the preceding 6 months ( as assessed by HbA1C ) participated in the study . They were r and omised to receive a st and ard preparation of Kothala Himbutu tea for 3 months followed by placebo in similar tea bags for a further 3 months ( n = 28 ) or in reverse order ( n = 23 ) . All patients received detailed advice on diet , exercise and lifestyle modification . HbA1C was measured at recruitment , at 3 months and on completion of the study at 6 months . Liver and renal functions were assessed biochemically at baseline , at 3 and 6 months and adverse events were recorded . There were no significant differences between the two groups in age , body mass index , male/female ratio , glycaemic control and baseline laboratory tests . All patients completed both arms of the trial . The HbA1C at the end of drug treatment was significantly lower than after treatment with placebo ( 6.29 + /- S.D. 1.02 versus 6.65 + /- S.D. 1.04 ; P = 0.008 ) . A statistically significant fall in HBA1c was seen with the active drug compared to a rise in HbA1C with the placebo group ( 0 . 54 + /- S.D. 0.93 ) versus -0.3 + /-S.D. 1.05 ; P < 0.001 . The daily mean dose of Glibenclamide fell by 1.89 ( S.D. 6.2 ) mg in the drug treated group but rose by 2.25 mg in the placebo treated group ( P = 0.07 ) . The differences in the metformin dose were not significantly significant in the two groups . We conclude that Kothala Himbutu tea is an effective and safe treatment for type 2 diabetes Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease ( CVD ) . We investigated the clinical effectiveness of Pycnogenol , a flavonoid-rich dietary supplement , in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes . Forty-eight individuals were enrolled in a r and omized , double-blind , placebo-controlled trial with parallel-group design . Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme ( ACE ) inhibitors .  Subjects were r and omly assigned to receive either Pycnogenol pill ( 125 mg daily ) or matched placebo for 12 weeks . According to the values of blood pressure ( BP ) measured at 2-week intervals , the pretrial ACE inhibitor dosage was left unchanged , reduced by 50 % , or brought back to the pretrial dosage until a stable BP was obtained . Fasting plasma glucose , low-density lipoprotein ( LDL ) cholesterol , glycosylated hemoglobin ( HbA1c ) , serum endothelin-1 , and urinary albumin were evaluated monthly . Pycnogenol treatment achieved BP control in 58.3 % of subjects at the end of the 12 weeks with 50 % reduction in individual pretrial dose of ACE-inhibitors ( P < .05 ) . Plasma endothelin-1 decreased by 3.9 pg/mL in Pycnogenol-treated group vs 0.5 pg/mL increase in control group ( P < .001 ) . Mean HbA1c dropped by 0.8 % in Pycnogenol-treated group ( P < .05 ) , whereas it decreased by 0.1 % in control group . Fasting plasma glucose declined by 23.7 mg/dL in Pycnogenol-treated group vs 5.7 mg/dL in control group ( P < .0001 ) . Low-density lipoprotein cholesterol improved significantly in Pycnogenol-treated group , declining by 12.7 mg/dL ( P < .001 ) . A significant decrease in urinary albumin level was observed at week 8 compared with the control group ( P < .05 ) . However , this reduction was not significant at 12th week . After 12 weeks of supplementation , Pycnogenol result ed in improved diabetes control , lowered CVD risk factors , and reduced antihypertensive medicine use vs controls Oxidative stress is increased postpr and ially and during long-term hyperglycemia in type 2 diabetic patients who present with poor response to glibenclamide . This study was design ed to evaluate the effects of the antioxidant flavonoid silymarin in improving long-term and postpr and ial glycemic and weight control in type 2 diabetic patients treated with glibenclamide .  Using a r and omized , double-blind , placebo-controlled design , 59 type 2 diabetic patients , previously maintained on 10 mg/day glibenclamide and diet control , with poor glycemic control , were r and omized into three groups : the first two groups were treated with either 200 mg/day silymarin or placebo as adjuncts to glibenclamide , and the third group was maintained on glibenclamide alone for 120 days . Fasting and 4-hour postpr and ial plasma glucose , glycated hemoglobin ( HbA(1c ) ) , and body mass index ( BMI ) were evaluated at baseline and after 120 days . Compared with placebo , silymarin treatment significantly reduced both fasting and postpr and ial plasma glucose excursions , in addition to significantly reducing HbA(1c ) levels and BMI after 120 days . No significantly different effects were observed for placebo compared to glibenclamide alone . In conclusion , adjunct use of silymarin with glibenclamide improves the glycemic control targeted by glibenclamide , during both fasting and postpr and ially , an effect that may be related to increased insulin sensitivity in peripheral tissues BACKGROUND AND AIMS Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality . A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better underst and ing of this association . The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED ( PREvención con DIeta MEDiterránea ) cohort using individual food consumption records . METHODS AND RESULTS The PREDIMED study is a large , parallel-group , multicentre , r and omised , controlled 5-year feeding trial aim ed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease . A total of 7200 participants , aged 55 - 80 years , completed a vali date d 1-year food frequency question naire ( FFQ ) at baseline .  Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer data base on polyphenol content in foods . The mean total polyphenol intake was 820 ± 323 mg day⁻¹ ( 443 ± 218 mg day⁻¹ of flavonoids and 304 ± 156 mg day⁻¹ of phenolic acids ) . Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol . The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries . CONCLUSION In Mediterranean countries , such as Spain , the main dietary source of polyphenols is coffee and fruits , but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil Curcumin , the yellow pigment from the rhizoma of Curcuma longa , is a widely studied polyphenolic compound which has a variety of biological activity as anti-inflammatory and antioxidative agent . Genistein one of the flavonoids found in soybean and chickpeas inhibits DNA str and breaks acting as a direct scavenger of reactive oxygen species . Human serum albumin ( HSA ) with high affinity binding sites is a major transporter for delivering several endogenous compounds and drugs in vivo . The aim of this study was to examine the interactions of curcumin and genistein with human serum albumin at physiological conditions , using constant protein concentration and various pigment contents .  FTIR , UV-Visible , CD  and  fluorescence spectroscopic methods were used to analyse drug binding mode , the binding constant and the effects of pigment complexation on HSA stability and conformation . Structural analysis showed that curcumin and genistein bind HSA via polypeptide polar groups with overall binding constants of K(curcumin)=5.5 (+/-0.8)x10(4)M(-1 ) and K(genistein)=2.4 (+/-0.40)x10(4)M(-1 ) . The number of bound pigment ( n ) is 1.33 for curcumin and 1.49 for genistein . The HSA conformation was altered by pigment complexation with reduction of alpha-helix and increase of r and om coil and turn structures suggesting a partial protein unfolding OBJECTIVES Our goal was to test feasibility and efficacy of a dietary intervention based on daily intake of flavanol-containing cocoa for improving vascular function of medicated diabetic patients . BACKGROUND Even in fully medicated diabetic patients , overall prognosis is unfavorable due to deteriorated cardiovascular function . Based on epidemiological data , diets rich in flavanols are associated with a reduced cardiovascular risk . METHODS In a feasibility study with 10 diabetic patients , we assessed vascular function as flow-mediated dilation ( FMD ) of the brachial artery , plasma levels of flavanol metabolites , and tolerability after an acute , single-dose ingestion of cocoa , containing increasing concentrations of flavanols ( 75 , 371 , and 963 mg ) . In a subsequent efficacy study , changes in vascular function in 41 medicated diabetic patients were assessed after a 30-day , thrice-daily dietary intervention with either flavanol-rich cocoa ( 321 mg flavanols per dose ) or a nutrient-matched control ( 25 mg flavanols per dose ) . Both studies were undertaken in a r and omized , double-masked fashion . Primary and secondary outcome measures included changes in FMD and plasma flavanol metabolites , respectively . RESULTS A single ingestion of flavanol-containing cocoa was dose-dependently associated with significant acute increases in circulating flavanols and FMD ( at 2 h : from 3.7 + /- 0.2 % to 5.5 + /- 0.4 % , p < 0.001 ) . A 30-day , thrice-daily consumption of flavanol-containing cocoa increased baseline FMD by 30 % ( p < 0.0001 ) , while acute increases of FMD upon ingestion of flavanol-containing cocoa continued to be manifest throughout the study . Treatment was well tolerated without evidence of tachyphylaxia . Endothelium-independent responses , blood pressure , heart rate , and glycemic control were unaffected . CONCLUSIONS Diets rich in flavanols reverse vascular dysfunction in diabetes , highlighting therapeutic potentials in cardiovascular disease AIM OF THE STUDY The aim of this r and omized and double blinded pilot clinical trial was to investigate the anti-diabetic efficacy of the Rauvolfia-Citrus ( RC ) tea in humans . We have earlier shown that a combination of calorie-restriction and chronic administration of the RC tea to the genetic diabetic ( BKS-db ) mice result ed in the normalization of blood sugar , reduction in lipid accumulated in the mice eyes and prevention of the degeneration of the otherwise brittle BKS-db pancreas . The tea is made by boiling foliage of Rauvolfia vomitoria and fruits of Citrus aurantium and is used to treat diabetes in Nigerian folk medicine . MATERIAL S AND METHODS The RC tea was produced using the Nigerian traditional recipe and tested in the traditional dosage on 23 Danish type 2 diabetes ( T2D ) patients . The participants were divided into two equivalent groups after stratification by sex , age and BMI , in a 4-month double-blinded , placebo-controlled and r and omized clinical trial . Most of the study subjects ( 19/23 ) were using oral anti-diabetic agents ( OADs ) . Mean disease duration was 6±4.6 years , mean age was 64±7 years and mean BMI was 28.7±3.8 kg/m(2 ) . Prior to starting the treatment , the participants received individual dietician consultations . RESULTS At the end of the 4-month treatment period , the treated group showed an 11 % decrease in 2-h postpr and ial plasma glucose relative to the 3 % increase in the placebo group ( p=0.004 ) . The improvement in blood glucose clearance with RC tea treatment was reflected in a 6 % reduction in HbA(1c ) ( p=0.02 ) and in a 10 % reduction in fasting plasma glucose ( p=0.02 ) , when comparing the post 4-month treatment to pre-treatment baseline values . Though the basal levels of phosphorylated acetyl CoA carboxylase enzyme in skeletal muscle were significantly reduced in the treated group ( p=0.04 ) , as compared to the placebo , only the pattern of reductions in the tissue fatty acids ( FAs ) differed in the two groups . While all types of FAs were reduced in placebo , only saturated ( SFA ) and monounsaturated ( MUFA ) FAs were reduced with treatment . Interestingly , a modest increase in the polyunsaturated FAs fraction was observed in the RC treated group . In addition , the reduction in SFA and MUFA with RC tea treatment came solely from the triglyceride fractions , as there was an increase in the skeletal muscle phospholipids . CONCLUSIONS Chronic administration of the RC tea to overweight T2D on OADs caused significant improvements in markers of glycaemic control and modifications to the fatty acid profile of skeletal muscle , without adverse effects or hypoglycaemia . Further exploration of the anti-diabetic effects of the RC tea is warranted Numerous studies have shown that resveratrol ( RES ) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited . Furthermore , the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood . Therefore , the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( P BMC s ) associated to the one-year daily intake of a RES enriched ( 8 mg ) grape extract ( GE-RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ) . We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES . We also examined the changes in several serobiochemical variables , inflammatory and fibrinolytic markers . Our results showed that supplementation with GE or GE-RES did not affect body weight , blood pressure , glucose , HbA1c or lipids , beyond the values regulated by gold st and ard medication in these patients . We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels . The expression of the pro-inflammatory cytokines CCL3 , IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in P BMC s from patients taking the GE-RES extract . Also , a group of miRs involved in the regulation of the inflammatory response : miR-21 , miR-181b , miR-663 , miR-30c2 , miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months . Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients Context Several studies suggest that blood glucose levels are associated with cardiovascular disease , even at blood glucose values that do not meet diagnostic criteria for diabetes . Contribution Among adult residents of Norfolk , United Kingdom , there was a continuous relationship between hemoglobin A1c levels and cardiovascular disease and total mortality . This relationship was apparent even among persons without diabetes . Implication s These observations justify the need for studies that address whether improvements in glycemic control might improve health outcomes in persons who do not have diabetes . The Editors Diabetes mellitus is of major and increasing global public health importance ( 1 ) . Persons with diabetes are at increased risk for premature disability and death associated with vascular , renal , retinal , and neuropathic complications . Raised fasting and postchallenge blood glucose levels in an oral glucose tolerance test are used to diagnose diabetes . The diagnostic threshold is based on the shape of the risk curve between glucose levels and specific microvascular complications of diabetes ( 2 - 6 ) . Diabetes also increases the risk for macrovascular diseases , such as coronary heart disease and stroke ( 7 ) . In contrast to microvascular disease , increasing evidence suggests that the relationship between blood glucose level and macrovascular disease is continuous and does not have an obvious threshold ( 2 , 8 , 9 ) . Hemoglobin A1c concentration is an indicator of average blood glucose concentrations over the preceding 3 months ; it is useful for characterizing dysglycemia in population studies because it is simpler to perform than the oral glucose tolerance test ( 10 ) . In a 3-year follow-up of men in a prospect i ve study , we previously reported that hemoglobin A1c concentrations were related to cardiovascular disease and all-cause mortality ( 11 ) . However , we had insufficient power to examine risk relationships at concentrations close to the diagnostic threshold of 7 % or to examine the relationship in women . We report the relation between hemoglobin A1c concentrations and fatal and nonfatal coronary heart disease , cardiovascular disease events , and all-cause mortality in men and women after an average of 6 years of follow-up . Methods The European Prospect i ve Investigation into Cancer in Norfolk ( EPICNorfolk ) is a prospect i ve population study of 25 623 men and women who were between 40 and 79 years of age and who resided in Norfolk , United Kingdom . Participants were recruited from general practice registers . Information on the recruitment process is available elsewhere ( 12 ) . Between 1993 and 1997 , participants completed a health and lifestyle question naire . Participants were asked whether a doctor had ever told them that they have any of the conditions contained in a list that included diabetes , heart attack , and stroke . People with known diabetes were defined as those who responded yes to the diabetes option of this question . Smoking history was derived from responses ( yes or no ) to the questions : Have you ever smoked as much as 1 cigarette a day for as long as a year ? and Do you smoke cigarettes now ? At a clinic , trained nurses performed a health examination for each participant . Body mass index was estimated as weight (kg)/height ( m2 ) , and waist-to-hip ratio was determined by measurements of the circumference of the waist and hips . Blood pressure was measured by using an Accutorr ( Data scope , Mahwah , New Jersey ) noninvasive  blood pressure  monitor after the participant had been seated for 5 minutes . The mean of 2 readings was used for analysis . Nonfasting blood sample s were taken ; sample s for assay were stored in a refrigerator at 4 C until transport within 1 week of sampling to the Department of Clinical Biochemistry , University of Cambridge . Starting in 1995 , hemoglobin A1c was measured on fresh EDTA blood sample s by using high-performance liquid chromatography ( BioRad Diamat Automated Glycosylated Haemoglobin Analyser , Hemel Hempstead , United Kingdom ) . We report results for follow-up to January 2003 , an average of about 6 years . All participants were flagged for death certification at the Office of National Statistics ; vital status was obtained for the entire cohort . Trained nosologists coded death certificates according to the International Classification of Diseases , Ninth or Tenth Revisions ( ICD-9 or ICD-10 ) . Cardiovascular death ( stroke , coronary heart disease , and other vascular causes ) was defined as those whose underlying cause of death was coded as ICD-9 400448 or ICD-10 I10I79 . Death from coronary heart disease was defined as those whose cause of death was coded as ICD-9 410414 or ICD-10 I22I25 . Participants admitted to a hospital were identified by their National Health Service number . Hospitals were linked to the East Norfolk Health Authority data base , which identifies all hospital contacts throughout Engl and and Wales for Norfolk residents . We used the same ICD diagnostic codes described in the preceding paragraphs to ascertain hospital episodes of cardiovascular disease and coronary heart disease in our cohort . Participants were identified as having a coronary heart disease event during follow-up if they had a hospital admission or died with coronary heart disease as the cause of death . Of the coronary heart disease events identified , 21 % ( 112 of 529 ) were fatal ; of the cardiovascular disease events , 23 % ( 197 of 806 ) were fatal . In men , 24 % ( 76 of 321 ) of deaths were attributed to heart disease and 29 % ( 117 of 321 ) were attributed to cardiovascular disease . In women , 18 % ( 36 of 200 ) of deaths were attributed to heart disease and 35 % ( 70 of 200 ) were attributed to cardiovascular causes . The Norwich Ethics Committee approved the study , and participants gave signed informed consent . Statistical Analysis These analyses , undertaken by using SPSS software , version 10.0 ( SPSS , Inc. , Chicago , Illinois ) , included 10 232 men and women age 45 to 79 years who completed the health and lifestyle question naire and had available hemoglobin A1c measurements . We divided the cohort into 7 categories on the basis of baseline data : known diabetes , high likelihood of previously undiagnosed diabetes ( no personal history of diabetes but a hemoglobin A1c concentration 7 % ) , and hemoglobin A1c concentrations in 0.5percentage point intervals ( < 5 % , 5 % to 5.4 % , 5.5 % to 5.9 % , 6.0 % to 6.4 % , and 6.5 % to 6.9 % ) . We examined risk factor distributions and then coronary heart disease , cardiovascular disease , and all-cause mortality rates by hemoglobin A1c and diabetes category . Age-adjusted odds ratios were calculated by using logistic regression models . We used a Cox proportional hazards model to determine the independent contribution of hemoglobin A1c to total mortality and cardiovascular and coronary heart disease after adjustment for age , body mass index , waist-to-hip ratio , systolic blood pressure , blood cholesterol concentrations , cigarette smoking , and history of heart attack or stroke . Participants with missing baseline data for 1 or more risk factors ( 130 men and 186 women ) were excluded from the multivariate analyses . Role of the Funding Sources The funding sources had no role in the design , conduct , and reporting of the study or in the decision to su bmi t the manuscript for publication . Results Table 1 presents characteristics of the participants according to hemoglobin A1c concentration and self-reported diabetes . Those with known diabetes had higher mean ( SD ) hemoglobin A1c concentrations ( 8.0 % 1.9 % ) than the rest of the study sample ( 5.3 % 0.7 % ) . They were older and had a higher body mass index , waist-to-hip ratio , and systolic blood pressure ; they were also more likely to report having had a previous heart attack or stroke . Participants with probable but previously undiagnosed diabetes ( hemoglobin A1c 7 % ) shared these characteristics . Mean risk factor levels rose with increasing concentration of hemoglobin A1c less than 7 % . Table 1 . Distribution of Variables by  Hemoglobin A1c Concentration and Known Diabetes in 4662 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 1997 ) Table 2 shows adjusted odds ratios for hemoglobin A1c concentrations , diabetes status , and outcomes .  Persons with known or undiagnosed diabetes had a greater risk for all-cause mortality and cardiovascular or coronary heart disease than those without diabetes . Risk for coronary heart or cardiovascular disease and total mortality increased throughout the whole range of hemoglobin A1c concentrations ; those with hemoglobin A1c concentrations less than 5 % had the lowest rates . For men , a gradient of increasing rates through the distribution was apparent for all end points . For women , odds ratios for cardiovascular or coronary heart disease did not increase significantly until the hemoglobin A1c concentration reached 6 % ; odds ratios were very high in women with concentrations greater than 7 % . Table 2 . Rates and Age-Adjusted Relative Risks for Total Coronary Heart Disease Events , Cardiovascular Disease Events , and All-cause Mortality by Category of Hemoglobin A1c Concentration and Known Diabetes in 4462 Men and 5570 Women Age 45 to 79 Years ( European Prospect i ve Investigation into Cancer in Norfolk , 1995 to 2003 ) Table 3 shows outcomes after adjustment for age alone and then after adjustment for age and other risk factors . In men , known diabetes predicted coronary heart and cardiovascular disease events and total mortality with approximate 2-fold relative risks . These relative risks were only slightly attenuated after adjustment for known risk factors . In women , known diabetes status predicted an approximate 5-fold increase in risk for coronary heart and 3-fold increase in risk for cardiovascular disease events ; these increases were attenuated after adjustment for known risk factors to 3-fold and 2-fold risk , respectively . In men and women , hemoglobin A1c concentrations predicted an increased risk for We have recently reported that ingestion of Ginkgo biloba extract ( EGb 761 ) ( a ) significantly reduced collagen-induced platelet aggregation and thromboxane B2 ( TXB2 ) production in both non-diabetic individuals as well as those with type 2 diabetes mellitus ( T2DM ) , ( b ) significantly reduced platelet malondialdehyde ( MDA ) , an index of lipid peroxidation , in non-diabetic subjects . In the present study we report that ingestion of EGb 761 ( 120 mg daily for 3 months ) , significantly decreased platelet MDA-thiobarbituric acid reacting substances ( TBARS ) ( 41 + /- 9 pmol/10(7 ) platelets versus 30 + /- 11 pmol/10(7 ) platelets ) ( p < 0.005 ) in T2DM subjects with normal cholesterol levels ( total cholesterol , 164 + /- 22 mg/dl ; age , 54 + /- 9 years ; BMI , 35.0 + /- 8.8 kg/m2 , n = 12 ) . In T2DM subjects with high cholesterol ( total cholesterol , 218 + /- 15 mg/dl ; age , 52 + /- 5 years ; BMI , 36.2 + /- 6.6 kg/m2 , n = 7 ) , EGb 761 ingestion reduced the platelet TBARS from 29 + /- 9 to 22 + /- 9 pmol/10(7 ) platelets ( p < 0.04 ) . Because ingestion of EGb 761 did not alter platelet counts it is concluded that EGb 761 , probably due to the flavonoid fraction , reduced the TBARS by inhibiting cyclooxygenase (COX)-1-mediated arachidonic acid oxygenation or by reducing the arachidonic acid pool . This is likely to lead to a reduction of platelet hyperactivity , a significant contributor to the development of cardiovascular disease in T2DM patients . Because of other reported beneficial properties of EGb 761 , such as stimulation of pancreatic beta-cell function in T2DM subjects with pancreatic exhaustion , it appears that T2DM subjects might benefit from ingesting EGb 761 as a dietary supplement
target: In conclusion , polyphenols can successfully reduce HbA1c in T2DM without any intervention at glycemia , and could contribute to the prevention of diabetes complications
background: ABSTRACT Polyphenols have been extensively studied for their antioxidant and anti-inflammatory properties .
  Recently , their antiglycative actions by oxidative stress modulation have been linked to the prevention of diabetes and associated complications .
  This article assesses the evidence for polyphenol interventions on glycohemoglobin ( HbA1c ) in non-diabetic , pre-diabetic , and type 2 diabetes mellitus ( T2DM ) subjects .