Efficacy of Turmeric as Adjuvant Therapy in Type 2 Diabetic Patients Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients 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 Effect of Ginkgo biloba and Camellia sinensis Extracts on Psychological State and Glycemic Control in Patients with Type 2 Diabetes Mellitus Molecular detection of exercise-induced free radicals following ascorbate prophylaxis in type 1 diabetes mellitus: a randomised controlled trial The Therapeutic Potential of Resistant Starch in Modulation of Insulin Resistance, Endotoxemia, Oxidative Stress and Antioxidant Biomarkers in Women with Type 2 Diabetes: A Randomized Controlled Clinical Trial The effects of non-surgical periodontal treatment on glycemic control, oxidative stress balance and quality of life in patients with type 2 diabetes: A randomized clinical trial The effects of aerobic exercise training at two different intensities in obesity and type 2 diabetes: implications for oxidative stress, low-grade inflammation and nitric oxide production Very low-dose fluvastatin-valsartan combination decreases parameters of inflammation and oxidative stress in patients with type 1 diabetes mellitus. Bilberry juice modulates plasma concentration of NF-κB related inflammatory markers in subjects at increased risk of CVD Systemic Cytokines in Type 2 Diabetes Mellitus and Chronic Periodontitis. Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Coffee polyphenol consumption improves postprandial hyperglycemia associated with impaired vascular endothelial function in healthy male adults. Antioxidant Effects of Zinc Supplementation in Tunisians with Type 2 Diabetes Mellitus Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. An anthocyanin/polyphenolic‐rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats. Diet, Inflammation, and Glycemic Control in Type 2 Diabetes: An Integrative Review of the Literature Effect of non-surgical periodontal treatment on visfatin concentrations in serum and gingival crevicular fluid of patients with chronic periodontitis and type 2 diabetes mellitus. Ineffectiveness of allopurinol in reduction of oxidative stress in diabetic patients; a randomized, double-blind placebo-controlled clinical trial. Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans. Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate Effects of coenzyme Q10 supplementation on serum values of adiponectin, leptin, 8-isoprostane and malondialdehyde in women with type 2 diabetes
Abstract It is known that there is a significant interplay of insulin resistance , oxidative stress , dyslipidemia , and inflammation in type 2 diabetes mellitus ( T2DM ) . The study was undertaken to investigate the effect of turmeric as an adjuvant to anti-diabetic therapy . Sixty diabetic subjects on metformin therapy  were recruited and r and omized into two groups ( 30 each ) . Group I received st and ard metformin treatment while group II was on st and ard metformin therapy with turmeric ( 2 g ) supplements for 4 weeks . The biochemical parameters were assessed at the time of recruitment for study and after 4 weeks of treatment . Turmeric supplementation in metformin treated type 2 diabetic patient significantly decreased fasting glucose ( 95 ± 11.4 mg/dl , P < 0.001 ) and HbA1c levels ( 7.4 ± 0.9 % , P < 0.05 ) . Turmeric administered group showed reduction in lipid peroxidation , MDA ( 0.51 ± 0.11 µmol/l , P < 0.05 ) and enhanced total antioxidant status ( 511 ± 70 µmol/l , P < 0.05 ) . Turmeric also exhibited beneficial effects on dyslipidemia LDL cholesterol ( 113.2 ± 15.3 mg/dl , P < 0.01 ) , non HDL cholesterol ( 138.3 ± 12.1 mg/dl , P < 0.05 ) and LDL/HDL ratio ( 3.01 ± 0.61 , P < 0.01 ) and reduced inflammatory marker , hsCRP ( 3.4 ± 2.0 mg/dl , P < 0.05 ) . Turmeric supplementation as an adjuvant to T2DM on metformin treatment had a beneficial effect on blood glucose , oxidative stress and inflammation 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 OBJECTIVE To assess the clinical efficacy of nutritional amounts of grape polyphenols ( PPs ) in counteracting the metabolic alterations of high-fructose diet , including oxidative stress and insulin resistance ( IR ) , in healthy volunteers with high metabolic risk . RESEARCH DESIGN AND METHODS Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients ( 18 men and 20 women ) were r and omized in a double-blind controlled trial between a grape PP ( 2 g/day ) and a placebo ( PCB ) group . Subjects were investigated at baseline and after 8 and 9 weeks of supplementation , the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose . The primary end point was the protective effect of  grape PPs  on fructose-induced IR . RESULTS In the PCB group , fructose induced 1 ) a 20 % decrease in hepatic insulin sensitivity index ( P < 0.05 ) and an 11 % decrease in glucose infusion rate ( P < 0.05 ) as evaluated during a two-step hyperinsulinemic-euglycemic clamp , 2 ) an increase in systemic ( urinary F2-isoprostanes ) and muscle ( thiobarbituric acid – reactive substances and protein carbonylation ) oxidative stress ( P < 0.05 ) , and 3 ) a downregulation of mitochondrial genes and decreased mitochondrial respiration ( P < 0.05 ) . All the deleterious effects of fructose were fully blunted by grape PP supplementation . Antioxidative defenses , inflammatory markers , and main adipokines were affected neither by fructose nor by grape PPs . CONCLUSIONS A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR . The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition 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 Interest in finding natural antioxidants for use in food or medical material s to prevent free radical imbalance has increased considerably over the past years . The aim of this research was to evaluate changes in glycemic control and psychological state of patients with type 2 diabetes mellitus ( T2DM ) after use of antioxidant plant preparations .  Fifty-six patients with T2DM were r and omly allocated to receive st and ardized Ginkgo biloba L. leaves dry extract , green tea dry extract , or placebo capsules .  Diabetes glycemic control measured as glycated hemoglobin ( HbA1c ) level , antioxidant state and psychological data were evaluated at baseline , after 9 and 18 months of using either antioxidant preparations or placebo . The level of perceived stress lowered significantly after 9 months ( p=0.038 ) and 18 months ( p=0.030 ) , and the psychological aspect of quality of life significantly improved after 18 months ( p=0.019 ) of use of G. biloba extract . No significant differences were detected after using green tea extract . In patients using placebo , significant lowering of HbA1c level was observed after 18 months ( p=0.017 ) . In conclusion , antioxidant G. biloba leaf extract exhibited a mild effect on psychological state and a trend of improving glycemic control in patients with type 2 diabetes mellitus Abstract Aims /hypothesis Patients with type 1 diabetes mellitus are more susceptible than healthy individuals to exercise-induced oxidative stress and vascular endothelial dysfunction , which has important implication s for the progression of disease . Thus , in the present study , we design ed a r and omised double-blind , placebo-controlled trial to test the original hypothesis that oral prophylaxis with vitamin C attenuates rest and exercise-induced free radical-mediated lipid peroxidation in type 1 diabetes mellitus . Methods All data were collected from hospitalised diabetic patients . The electron paramagnetic resonance spectroscopic detection of spin-trapped α-phenyl-tert-butylnitrone ( PBN ) adducts was combined with the use of supporting markers of lipid peroxidation and non-enzymatic antioxidants to assess exercise-induced oxidative stress in male patients with type 1 diabetes ( HbA1c 7.9 ± 1 % , n = 12 ) and healthy controls ( HbA1c 4.6 ± 0.5 % , n = 14 ) . Following participant r and omisation using numbers in a sealed envelope , venous blood sample s were obtained at rest , after a maximal exercise challenge and before and 2 h after oral ingestion of 1 g ascorbate or placebo . Participants and lead investigators were blinded to the administration of either placebo or ascorbate treatments . Primary outcome was the difference in changes in free radicals following ascorbate ingestion . Results Six diabetic patients and seven healthy control participants were r and omised to each of the placebo and ascorbate groups . Diabetic patients ( n = 12 ) exhibited an elevated concentration of PBN adducts ( p < 0.05 vs healthy , n = 14 ) , which were confirmed as secondary , lipid-derived oxygen-centred alkoxyl ( RO · ) radicals ( anitrogen = 1.37 mT and aβhydrogen = 0.18 mT ) . Lipid hydroperoxides were also selectively elevated and associated with a depression of retinol and lycopene ( p < 0.05 vs healthy ) . Vitamin C supplementation  increased plasma vitamin C concentration to a similar degree in both groups ( p < 0.05 vs pre-supplementation ) and attenuated the exercise-induced oxidative stress response ( p < 0.05 vs healthy).There were no selective treatment differences between groups in the primary outcome variable . Conclusions /interpretationThese findings are the first to suggest that oral vitamin C supplementation provides an effective prophylaxis against exercise-induced free radical-mediated lipid peroxidation in human diabetic blood . Clinical trials registration number : IS RCT N96164937 Funding : No external funding Aims : This trial aims to determine the effects of resistant starch ( RS ) subtype 2 ( RS2 ) on glycemic status , metabolic endotoxemia and markers of oxidative stress . Methods : A r and omized , controlled , parallel-group clinical trial group of 56 females with type 2 diabetes mellitus ( T2DM ) was divided to 2 groups . The intervention group ( n = 28 ) and control group ( n = 28 ) received 10 g/day RS2 or placebo for 8 weeks , respectively . Fasting blood sample s were taken to determine glycemic status , endotoxin , high sensitivity C-reactive protein ( hs-CRP ) , malondialdehyde ( MDA ) , total antioxidant capacity ( TAC ) , antioxidant enzymes concentrations as well as uric acid at baseline and after the intervention . Results : After 8 weeks , RS2 caused a significant decrease in the levels of MDA ( -34.10 % ) , glycosylated hemoglobin ( -9.40 % ) , insulin ( -29.36 % ) , homeostasis model of insulin resistance ( -32.85 % ) and endotoxin ( -25.00 % ) , a significant increase in TAC ( 18.10 % ) and glutathione peroxidase ( 11.60 % ) as compared with control . No significant changes were observed in fasting plasma glucose , quantitative insulin sensitivity check index , hs-CRP , superoxide dismutase , catalase and uric acid in the RS2 group as compared with the control group . Conclusion : Supplementation with RS2 may be improved glycemic status , endotoxemia and markers of oxidative stress in patients with T2DM Aim The purpose of this study was to investigate the effects of non-surgical periodontal treatment on hemoglobinA1c ( HbA1c ) levels , oxidative stress balance and quality of life ( QOL ) in patients with type 2 diabetes mellitus ( T2DM ) compared to no periodontal treatment ( simple oral hygiene instructions only ) . Methods The design was a 6-month , single-masked , single center , r and omized clinical trial . Patients had both T2DM and chronic periodontitis . Forty participants were enrolled between April 2014 and March 2016 at the Nephrology , Diabetology and Endocrinology Department of Okayama University Hospital . The periodontal treatment group ( n = 20 ) received non-surgical periodontal therapy , including scaling and root planing plus oral hygiene instructions , and consecutive supportive periodontal therapy at 3 and 6 months . The control group ( n = 17 ) received only oral hygiene instructions without treatment during the experimental period . The primary study outcome was the change in HbA1c levels from baseline to 3 months . Secondary outcomes included changes in oxidative stress balance ( Oxidative-INDEX ) , the Diabetes Therapy-Related QOL and clinical periodontal parameters from baseline to 3 months and baseline to 6 months . Results Changes in HbA1c in the periodontal treatment group were not significantly different with those in the control group at 3 and 6 months . Systemic oxidative stress balance and QOL significantly improved in the periodontal treatment group compared to the control group at 3 months . In the subgroup analysis ( moderately poor control of diabetes ) , the decrease in HbA1c levels in the periodontal treatment group was greater than that in the control group at 3 months but not significant . Conclusions In T2DM patients , non-surgical periodontal treatment improved systemic oxidative stress balance and QOL , but did not decrease HbA1c levels at 3 months follow-up . Trial registration Current Controlled Trials UMIN-ICDR UMIN 000013278 ( Registered April 1 , 2014 ) Aims To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide ( tNOx ) availability and iNOS/nNOS expression , oxidative stress ( OS ) and inflammation in obese humans with or without type 2 diabetes mellitus ( T2DM ) . Methods Twenty-five sedentary , obese ( BMI > 30 kg/m2 ) males ( 52.8 ± 7.2 years ) ; 12 controls versus 13 T2DM were r and omly allocated to four groups that exercised for 30 min , three times per week either at low ( Fat-Max ; 30–40 % VO2max ) or moderate ( Tvent ; 55–65 % VO2max ) intensity . Before and after training , blood and muscle sample s ( v. lateralis ) were collected . Results Baseline erythrocyte glutathione was lower ( 21.8 ± 2.8 vs. 32.7 ± 4.4 nmol/ml ) and plasma protein oxidative damage and IL-6 were higher in T2DM ( 141.7 ± 52.1 vs. 75.5 ± 41.6 nmol/ml ) . Plasma catalase increased in T2DM after Tvent training ( from 0.98 ± 0.22 to 1.96 ± 0.3 nmol/min/ml ) . T2DM groups demonstrated evidence of oxidative damage in response to training ( elevated protein carbonyls ) . Baseline serum tNOx were higher in controls than T2DM ( 18.68 ± 2.78 vs. 12.34 ± 3.56 μmol/l ) . Training at Tvent increased muscle nNOS and tNOx in the control group only . Pre-training muscle nNOS was higher in controls than in T2DMs , while the opposite was found for iNOS . No differences were found after training for plasma inflammatory markers . Conclusion Exercise training did not change body composition or aerobic fitness , but improved OS markers , especially when performed at Tvent . Non-diabetics responded to Tvent training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM , perhaps due to higher insulin resistance ( unchanged after intervention ) AIMS Previously we revealed the effectiveness of a new therapeutic approach with a short-term , very-low dose fluvastatin-valsartan combination on the improvement of arterial function in type 1 diabetes mellitus patients ( T1DM ) . In this study we explored whether this approach influences inflammation and oxidative stress and explored any association of these effects with arterial function improvement . METHODS This was a supplementary analysis of the two previous double blind r and omized studies ( included 44 T1DM patients ) . Treatment group received very-low dose fluvastatin-valsartan , the control group received placebo . Blood sample s were collected and inflammation parameters : high-sensitivity CRP ( hsCRP ) , interleukin 6 ( IL-6 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) and oxidative stress parameter total antioxidant status ( TAS ) were measured . RESULTS Treatment decreased hsCRP values ( by 56.5 % , P<0.05 ) and IL-6 values ( by 33.6 % , P<0.05 ) and increased TAS values ( by 21.1 % ; P<0.05 ) after 30days of treatment . High sensitivity CRP and TAS remained decreased 3months after treatment discontinuation . Importantly , the anti-inflammatory and anti-oxidative action significantly correlated with arterial function improvement . CONCLUSIONS The approach consisting of short-term ( 30days ) treatment with a very low-dose fluvastatin-valsartan combination acts anti-inflammatory and anti-oxidative in T1DM patients . These observations along with the improvement of arterial function support the assumption that this approach could have an important clinical benefit in T1DM patients Purpose Bilberries are abundant in polyphenols . Dietary polyphenols have been associated with strategies for prevention and treatment of chronic inflammatory diseases . We investigated the effect of bilberry juice on serum and plasma biomarkers of inflammation and antioxidant status in subjects with elevated levels of at least one risk factor for cardiovascular disease ( CVD ) . Methods In a r and omized controlled trial , participants consumed either bilberry juice ( n = 31 ) or water ( n = 31 ) for 4 weeks . Results Supplementation with bilberry juice result ed in significant decreases in plasma concentrations of C-reactive protein ( CRP ) , interleukin (IL)-6 , IL-15 , and monokine induced by INF-γ ( MIG ) . Unexpectedly , an increase in the plasma concentration of tumor nuclear factor-α ( TNF-α ) was observed in the bilberry group . CRP , IL-6 , IL15 , MIG , and TNF-α are all target genes of nuclear factor- kappa B ( NF-κB ) , —a transcription factor that is crucial in orchestrating inflammatory responses . Plasma quercetin and p-coumaric acid increased in the bilberry group , otherwise no differences were observed for clinical parameters , oxidative stress or antioxidant status . Furthermore , we studied the effect of polyphenols from bilberries on lipopolysaccharide (LPS)-induced NF-κB activation in a monocytic cell line . We observed that quercetin , epicatechin , and resveratrol inhibited NF-κB activation . Conclusions These findings suggest that supplementation with bilberry polyphenols may modulate the inflammation processes . Further testing of bilberry supplementation as a potential strategy in prevention and treatment of chronic inflammatory diseases is warranted BACKGROUND Cytokine dysregulation plays an important role in Type 2 Diabetes Mellitus ( T2DM ) and Chronic Periodontitis ( CP ) with a commonality in pathogenic mechanisms . CP is considered the sixth complication of diabetes and may have an increased influence on systemic levels of cytokines in individuals with T2DM . OBJECTIVE This study investigated two pro- , and two presumed anti-inflammatory cytokines and their ratios in the serum of healthy individuals , in chronic periodontitis with and without T2DM with , and without CP and in CP alone aim ed at evaluating the systemic inflammatory burden of a local oral infection . METHODS Eighty participants were divided equally into four groups as healthy volunteers ( H ) and patients having T2DM with , and without CP ( T2DM+CP , and T2DM ) and only CP ( CP ) . Serum sample s were collected to measure glycated hemoglobin ( HbA1c ) , R and om Blood Sugar ( RBS ) and also Tumor Necrosis Factor (TNF)-α , Interleukin (IL)-4 , -6 - 10 were assessed using commercially available ELISA kits . RESULTS The cytokines were detected in all groups . Significant differences were observed between groups for all the clinical , biochemical parameters and cytokines . Cytokine levels and the ratios showed significant correlations . The ratios of the cytokines differed significantly amongst groups , were highest in T2DM+CP . CONCLUSION In this study , the cytokine ratios provided a qualitative profile along with the absolute levels in T2DM with periodontitis , indicative of an intensified systemic inflammatory state AIM To examine the role of placental protein tyrosine nitration and p38-Mitogen-Activated Protein Kinase α ( p38-MAPKα ) , Extra Cellular-Signal Regulated Kinase ( ERK ) and c-Jun NH2-Terminal Kinase ( JNK ) activity , in the pathogenesis of type 1 diabetic pre-eclampsia , and the putative modulation of these indices by maternal vitamin C and E supplementation . METHODS Placental sample s were obtained from a sub-cohort of the DAPIT trial : a r and omised placebo-controlled trial of antioxidant supplementation to reduce pre-eclampsia in type 1 diabetic pregnancy . Placenta from placebo-treated : normotensive ( NT ) [ n=17 ] , gestational hypertension ( GH ) [ n=7 ] and pre-eclampsia ( PE ) [ n=6 ] and vitamin-treated : NT ( n=20 ) , GH ( n=4 ) and PE ( n=3 ) was analysed . Protein tyrosine nitration was assessed by immunohistochemistry in paraffin-embedded tissue . Catalytic activities of placental p38-MAPKα , ERK and JNK were measured by enzyme-linked immunosorbent assay ( ELISA ) . RESULTS Nitrotyrosine immunostaining was present in placebo-treated NT , GH and PE placentae , with no significant difference observed between the groups . There was a non-significant trend towards decreased p38-MAPKα activity in PE vs NT control placentae . ERK and JNK were similar among the three outcome placebo groups and vitamin supplementation did not significantly alter their activity . CONCLUSION Nitrotyrosine immunopositivity in normotensive diabetic placentae indicates some degree of tyrosine nitration in uncomplicated diabetic pregnancy , possibly due to inherent oxidative stress and peroxynitrite production . Our results suggest that p38-MAPKα , ERK and JNK are not directly involved in the pathogenesis of type 1 diabetic pre-eclampsia and are not modulated by vitamin-supplementation BACKGROUND AND OBJECTIVES Increased inflammation and oxidative stress may be caused by proteins and lipids modified by cytotoxic advanced glycation end products ( AGEs ) in food . Restricting food containing elevated AGEs improves these risk factors in diabetic CKD . Because diet adherence can be problematic , this study aim ed to remove cytotoxic AGEs from food already ingested and to determine whether sevelamer carbonate sequesters cytotoxic AGEs in the gut , preventing their uptake and thereby reducing AGE-induced abnormalities . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This single-center , r and omized , 2-month , open-label , intention-to-treat , crossover study compared sevelamer carbonate with calcium carbonate  treatment in stage 2 - 4 diabetic CKD . Participants received 2 months of treatment with one drug , had a 1-week washout , and then received the opposite drug for 2 months . RESULTS Sevelamer carbonate  reduced HbA1c , serum methylglyoxal , serum (ε)N-carboxymethyl-lysine , triglycerides , and 8-isoprostanes . Total cholesterol and fibroblast growth factor 23 were reduced by sevelamer carbonate , relative to calcium carbonate  . AGE receptor 1 and sirtuin 1 mRNA were increased and PMNC TNFα levels were decreased by sevelamer carbonate , but not calcium carbonate . Medications and caloric and AGE intake remained unchanged . Sevelamer carbonate reversibly bound AGE-BSA at intestinal , but not stomach , pH. CONCLUSIONS Sevelamer carbonate significantly reduces HbA1c , fibroblast growth factor 23 , lipids , and markers of inflammation and oxidative stress , and markedly increases antioxidant markers , independently of phosphorus in patients with diabetes and early kidney disease . These novel actions of sevelamer carbonate on metabolic and inflammatory abnormalities in type 2 diabetes mellitus may affect progression of early diabetic CKD Epidemiological studies indicate that habitual coffee consumption lowers the risk of diabetes and cardiovascular diseases . Postpr and ial hyperglycemia is a direct and independent risk factor for cardiovascular diseases . We previously demonstrated that coffee polyphenol ingestion increased secretion of Glucagon-like peptide 1 ( GLP-1 ) , which has been shown to exhibit anti-diabetic and cardiovascular effects . We hypothesized coffee polyphenol consumption may improve postpr and ial hyperglycemia and vascular endothelial function by increasing GLP-1 release and /or reducing oxidative stress . To examine this hypothesis , we conducted a r and omized , acute , crossover , intervention study in healthy male adults , measuring blood parameters and flow-mediated dilation ( FMD ) after ingestion of a meal with or without coffee polyphenol extract ( CPE ) .  Nineteen subjects consumed a test meal with either a placebo- or CPE-containing beverage .  Blood biomarkers and FMD were measured at fasting and up to 180 minutes postpr and ially . The CPE beverage led to a significantly lower peak postpr and ial increase in blood glucose and diacron-reactive oxygen metabolite , and significantly higher postpr and ial FMD than the placebo beverage . Postpr and ial blood GLP-1 increase tended to be higher after ingestion of the CPE beverage , compared with placebo . Subclass analysis revealed that the CPE beverage significantly improved postpr and ial blood GLP-1 response and reduced blood glucose increase in the subjects with a lower insulinogenic index . Correlation analysis showed postpr and ial FMD was negatively associated with blood glucose increase after ingestion of the CPE beverage . In conclusion , these results suggest that coffee polyphenol consumption improves postpr and ial hyperglycemia and vascular endothelial function , which is associated with increased GLP-1 secretion and decreased oxidative stress in healthy humans Objective : To determine the effects of zinc ( Zn ) supplementation on oxidative stress in persons with type 2 diabetes mellitus ( type 2 DM ) . Design : Tunisian adult subjects with HbA1c > 7.5 % were supplemented for six months with 30 mg/day of Zn as Zn gluconate or placebo . The effects of supplementation on plasma zinc ( Zn ) , copper ( Cu ) , urinary Zn , plasma thiobarbituric acid reactive substances ( TBARS ) , Cu-Zn superoxide dismutase ( SOD ) and glutathione peroxidase activities ( GPX ) in red blood cells , blood lipids and lipoproteins , HbA1c and fasting glucose were measured at the beginning of the study and after three and six months . Results : At the beginning of the study , more than 30 % of the subjects exhibited plasma Zn values less than the normal minimum of 10.7 μmol/L , whereas levels of plasma Cu and antioxidant RBC Cu-Zn SOD and GPx enzyme activities were in the normal ranges . Oxidative stress , monitored by plasma TBARS , was increased in individuals with diabetes compared with healthy Tunisian subjects ( 3.32 ± 0.05 μmol/L vs. 2.08 ± 0.04 μmol/L ) and an inverse correlation was found between Zn plasma levels and plasma TBARS . After three and six months of Zn supplementation , all of the subjects exhibited plasma Zn values greater than 10.7 μmol/L. There was a decrease of plasma TBARS in Zn supplemented group after six months ( 15 % ) with no significant changes in the placebo group . Supplementation did not alter significantly HbA1c nor glucose homeostasis . No adverse effects of Zn supplementation were observed on Cu status or HDL cholesterol . Conclusions : These data suggest the potential beneficial antioxidant effects of Zn supplementation in persons with type 2 DM . These results are particularly important in light of the deleterious consequences of oxidative stress in persons with diabetes BACKGROUND Diabetes and periodontitis are complex chronic diseases with an established bidirectional relationship . There is long-established evidence that hyperglycaemia in diabetes is associated with adverse periodontal outcomes . However , given the ubiquity of periodontal diseases and the emerging global diabetes epidemic , the complications of which contribute to significant morbidity and premature mortality , it is timely to review the role of periodontitis in diabetes . AIMS To report the epidemiological evidence from cross-sectional , prospect i ve and intervention studies for the impact of periodontal disease on diabetes incidence , control and complications and to identify potential underpinning mechanisms . EPIDEMIOLOGY Over the last 20 years , consistent and robust evidence has emerged that severe periodontitis adversely affects glycaemic control in diabetes and glycaemia in non-diabetes subjects . In diabetes patients , there is a direct and dose-dependent relationship between periodontitis severity and diabetes complications . Emerging evidence supports an increased risk for diabetes onset in patients with severe periodontitis . BIOLOGICAL MECHANISMS Type 2 diabetes is preceded by systemic inflammation , leading to reduced pancreatic β-cell function , apoptosis and insulin resistance . Increasing evidence supports elevated systemic inflammation ( acute-phase and oxidative stress biomarkers ) result ing from the entry of periodontal organisms and their virulence factors into the circulation , providing biological plausibility for the effects of periodontitis on diabetes . AGE ( Advanced Glycation Endproducts)-RAGE ( Receptor for AGEs ) interactions and oxidative-stress-mediated pathways provide plausible mechanistic links in the diabetes to periodontitis direction . INTERVENTIONS R and omized controlled trials ( RCTs ) consistently demonstrate that mechanical periodontal therapy associates with approximately a 0.4 % reduction in HbA1C at 3 months , a clinical impact equivalent to adding a second drug to a pharmacological regime for diabetes . RCTs are needed with larger numbers of subjects and longer term follow-up , and if results are substantiated , adjunctive periodontal therapies subsequently need to be evaluated . There is no current evidence to support adjunctive use of antimicrobials for periodontal management of diabetes patients . GUIDELINES Given the current evidence , it is timely to provide guidelines for periodontal care in diabetes patients for medical and dental professionals and recommendations for patients /the public BACKGROUND AND OBJECTIVES The primary goals were to re-examine whether sevelamer carbonate ( SC ) reduces advanced glycation end products ( AGEs ) ( methylglyoxal and carboxymethyllysine [ CML ] ) , increases antioxidant defenses , reduces pro-oxidants , and improves hemoglobin A1c ( HbA1c ) in patients with type 2 diabetes mellitus ( T2DM ) and diabetic kidney disease ( DKD ) . Secondary goals examined albuminuria , age , race , sex , and metformin prescription . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This two-center , r and omized , intention-to-treat , open-label study evaluated 117 patients with T2DM ( HbA1c > 6.5 % ) and stages 2 - 4 DKD ( urinary albumin/creatinine ratio ≥200 mg/g ) treated with SC ( 1600 mg ) or calcium carbonate ( 1200 mg ) , three times a day , without changing medications or diet . Statistical analyses used linear mixed models adjusted for r and omization levels . Preselected subgroup analyses of sex , race , age , and metformin were conducted . RESULTS  SC lowered serum methylglyoxal ( 95 % confidence interval [ CI ] , -0.72 to -0.29 ; P<0.001 ) , serum CML ( 95 % CI , -5.08 to -1.35 ; P≤0.001 ) , and intracellular CML ( 95 % CI , -1.63 to -0.28 ; P=0.01 ) . SC increased anti-inflammatory defenses , including nuclear factor like-2 ( 95 % CI , 0.58 to 1.29 ; P=0.001 ) , AGE receptor 1 ( 95 % CI , 0.23 to 0.96 ; P=0.001 ) , NAD-dependent deacetylase sirtuin-1 ( 95 % CI , 0.20 to 0.86 ; P=0.002 ) , and estrogen receptor α ( 95 % CI , 1.38 to 2.73 ; P ≤0.001 ) . SC also decreased proinflammatory factors such as TNF receptor 1 ( 95 % CI , -1.56 to -0.72 ; P≤0.001 ) and the receptor for AGEs ( 95 % CI , -0.58 to 1.53 ; P≤0.001 ) . There were no differences in HbA1c , GFR , or albuminuria in the overall group . Subanalyses showed that  SC lowered HbA1c in women ( 95 % CI , -1.71 to -0.27 ; P=0.01 , interaction P=0.002 ) , and reduced albuminuria in those aged < 65 years ( 95 % CI , -1.15 to -0.07 ; P=0.03 , interaction P=0.02 ) and non-Caucasians ( 95 % CI , -1.11 to -0.22 ; P=0.003 , interaction P≤0.001 ) , whereas albuminuria increased after SC and calcium carbonate in Caucasians . CONCLUSIONS SC reduced circulating and cellular AGEs , increased antioxidants , and decreased pro-oxidants , but did not change HbA1c or the albumin/creatinine ratio overall in patients with T2DM and DKD . Because subanalyses revealed that SC may reduce HbA1c and albuminuria in some patients with T2DM with DKD , further studies may be warranted Oxidative cell damage is involved in the pathogenesis of atherosclerosis , cancer , diabetes and other diseases . Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols , might reduce oxidative cell damage . Therefore , an intervention study was performed with a red mixed berry juice [ trolox equivalent antioxidative capacity ( TEAC ) : 19.1 mmol/L trolox ] and a corresponding polyphenol‐depleted juice ( polyphenols largely removed , TEAC 2.4 mmol/L trolox ) , serving as control . After a 3‐week run‐in period , 18 male prob and s daily consumed 700 mL juice , and 9 consumed control juice , in a 4‐week intervention , followed by a 3‐week wash‐out . Sample s were collected weekly to analyze DNA damage ( comet assay ) , lipid peroxidation ( plasma malondialdehyde : HPLC/fluorescence ; urinary isoprostanes : GC‐MS ) , blood glutathione ( photometrically ) , DNA‐binding activity of nuclear factor‐κB ( ELISA ) and plasma carotenoid/α‐tocopherol levels ( HPLC‐DAD ) . During intervention with the fruit juice , a decrease of oxidative DNA damage ( p<5 × 10–4 ) and an increase of reduced glutathione ( p<5 × 10–4 ) and of glutathione status ( p<0.05 ) were observed , which returned to the run‐in levels in the subsequent wash‐out phase . The other biomarkers were not significantly modulated by the juice supplement . Intervention with the control juice did not result in reduction of oxidative damage . In conclusion , the fruit juice clearly reduces oxidative cell damage in healthy prob and 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 Type 2 diabetes ( T2D ) is a growing national health problem affecting 35 % of adults ≥20 years of age in the United States . Recently , diabetes has been categorized as an inflammatory disease , sharing many of the adverse outcomes as those reported from cardiovascular disease . Medical nutrition therapy is recommended for the treatment of diabetes ; however , these recommendations have not been up date d to target the inflammatory component , which can be affected by diet and lifestyle . To assess the current state of evidence for which dietary programs contain the most anti-inflammatory and glycemic control properties for patients with T2D , we conducted an integrative review of the literature . A comprehensive search of the PubMed , CINAHL , Scopus , and Web of Science data bases from January 2000 to May 2012 yielded 786 articles . The final 16 studies met the selection criteria including r and omized control trials , quasiexperimental , or cross-sectional studies that compared varying diets and measured inflammatory markers . The Mediterranean and DASH diets along with several low-fat diets were associated with lower inflammatory markers . The Mediterranean diet demonstrated the most clinical ly significant reduction in glycosylated hemoglobin ( HbA1c ) . Information on best dietary guidelines for inflammation and glycemic control in individuals with T2D is lacking . Continued research is warranted BACKGROUND This study aims to assess visfatin concentrations in serum and gingival crevicular fluid ( GCF ) and investigate this relationship in patients with type 2 diabetes mellitus ( T2DM ) and chronic periodontitis ( CP ) before and after non-surgical periodontal treatment .  METHODS Fifty-four patients with T2DM and CP were recruited . The patients were r and omly divided into two groups : treatment and control . Serum and GCF visfatin concentrations and glycated hemoglobin ( HbA1c ) levels  were measured by enzyme-linked immunosorbent assay at different time points ( at baseline and 3 and 6 months after non-surgical periodontal treatment ) . RESULTS Serum and GCF visfatin concentrations showed no significant differences between the groups at baseline ( t test , P > 0.05 ) . A significant decline of visfatin in the treatment group was found in serum and GCF 3 months after non-surgical periodontal treatment ( t test , P < 0.01 ) . Baseline and 3-month HbA1c levels were not significantly different , but at 6 months , a statistically significant difference was detected ( t test , P > 0.05 ) . CONCLUSIONS The data suggest that non-surgical periodontal treatment is helpful for glucose control , an effect that may be associated with reduced visfatin in patients with T2DM and periodontitis . Furthermore , the data suggest that visfatin may be considered an inflammatory marker for periodontal diseases The objective of this r and omized , double-blind placebo-controlled clinical trial was to evaluate the value of allopurinol treatment on reduction of oxidative stress in patients with diabetes type II patients . Forty-one diabetic type II subjects were r and omly assigned to two groups . One group ( n = 20 ) received 100 mg allopurinol three times a day for 14 days and the other group ( n = 21 ) received a placebo .  Blood and saliva sample s were collected before and after intervention for analysis of lipid peroxidation level and total antioxidant power as indices of oxidative stress . At the beginning of the study , the groups were similar based upon age , duration of diabetes , fasting glucose , and HbA1c . Both allopurinol and placebo were effective in reduction of lipid peroxidation and total antioxidant power whether in saliva or plasma in a similar extent . HbA1c and FBS levels did not change through the study neither in case or placebo group . It is concluded that allopurinol therapy is not more effective than placebo in reduction of oxidative stress in diabetic patients . The same trend of changes in blood and saliva shown for oxidative stress indices was interesting and suggests a chance for saliva to be valuable in diagnosis of oxidative stress . However , to elaborate the exact role of allopurinol in diabetes , further large r and omized clinical trials are needed BACKGROUND AND AIMS Epidemiological studies have demonstrated an association between high-polyphenol intake and reduced incidence of atherosclerosis . The healthy effects of cocoa-polyphenols may be due to their antioxidant and anti-inflammatory actions , although the exact mechanisms are unknown and depend on the matrix in which cocoa-polyphenols are delivered . Nuclear factor κB ( NF-κB ) is a key molecule in the pathophysiology of atherosclerosis involved in the regulation of adhesion molecules(AM ) and cytokine expression and its activation is the first step in triggering the inflammatory process . The aim of this study was to evaluate the effect of acute cocoa consumption in different matrices related to the bioavailability of cocoa-polyphenols in NF-κB activation and the expression of AM . METHODS AND RESULTS Eighteen healthy volunteers r and omly received 3 interventions : 40 g of cocoa powder with milk ( CM ) , with water ( CW ) , and only milk ( M ) . NF-κB activation in leukocytes and AM ( sICAM , sVCAM , E-selectin ) were measured before and 6h after each intervention . Consumption of CW significantly decreased NF-κB activation compared to baseline and to CM ( P < 0.05 , both ) , did not change after CM intervention , and significantly increased after M intervention ( P = 0.014 ) . sICAM-1 concentrations significantly decreased after 6h of CW and CM interventions ( P ≤ 0.026 ; both ) and E-selectin only decreased after CW intervention ( P = 0.028 ) . No significant changes were observed in sVCAM-1 concentrations . CONCLUSIONS The anti-inflammatory effect of cocoa intake may depend on the bioavailability of bioactive compounds and may be mediated at least in part by the modulation of NF-κB activation and downstream molecules reinforcing the link between cocoa intake and health Heading Abstract Aims /hypothesis . Patients with diabetes are characterised by endothelial dysfunction and cardiovascular mortality . In particular endothelium-derived nitric oxide has emerged as a first line mechanism against atherosclerosis . Hyperglycaemia causes oxygen radical stress but has also been associated with endothelial nitric oxide synthase uncoupling , both lead to decreased nitric oxide-availability . We recently showed that folate reverses eNOS uncoupling in vitro . Therefore we hypothesise that folate improves endothelial function in Type II ( non-insulin-dependent ) diabetes mellitus in vivo . Methods . Using forearm plethysmography , we evaluated the effect of local , intra-arterial administration of 5-methyltetrahydrofolate ( 5-MTHF , the active form of folic acid , 1 µg/100 ml FAV/min ) on forearm blood flow in 23 patients with Type II diabetes and 21 control subjects , matched for age , sex , blood pressure , body mass index , weight and smoking habits . Serotonin as a stimulator of nitric oxide-dependent vasodilation and sodium nitroprusside as a stimulator of endothelium-independent vasodilation were infused . Results . Serotonin-induced vasodilation was blunted ( 53±30 vs 102±66 M/C% , p<0.005 ) and nitroprusside-induced vasodilation was mildly reduced ( 275±146 vs 391±203 M/C% , p<0.05 ) in patients with Type II diabetes compared to control subjects . 5-MTHF  improved nitric oxide-mediated vasodilation ( from 53±30 to 88±59 M/C% , p<0.05 ) in patients with Type II diabetes mellitus . As expected , 5-MTHF had no effect on forearm blood flow in control subjects . Conclusion /interpretation . These data imply that folate can be used to improve nitric oxide status and to restore endothelial dysfunction in patients with Type II diabetes . Our results provide a strong rationale for the initiation of studies that investigate whether supplementation with folic acid prevents future cardiovascular events in this patient group Abstract Patients with type 2 diabetes mellitus ( T2DM ) have been known to be suffering from coenzyme Q10 ( CoQ10 ) deficiency which results in some complications in them . The purpose of this clinical trial study was to evaluate the effects of CoQ10 supplementation on serum values of adiponectin ( A ) , leptin ( L ) , 8-isoprostane , malondialdehyde ( MDA ) , the A/L ratio in women with T2DM . Sixty-eight women with T2DM were enrolled in the current study and were r and omly divided into drug ( n = 34 ) and placebo ( n = 34 ) groups who were consuming 100 mg CoQ10 and 100 mg cellulose acetate per day for 12 weeks , respectively . Measurements were performed at the beginning and after the intervention . Serum values of adiponectin ( p = .001 ) and the A/L ratio ( p = .001 ) were increased while values of leptin ( p = .041 ) , MDA ( p = .023 ) , 8-isoprostane ( p = .004 ) were decreased significantly in drug group after intervention . This study had shown that CoQ10 supplementation in women with T2DM was effective in elevation of adiponectin and the A/L ratio and reduction of leptin , MDA and 8-isoprostane which could result in improving insulin resistance and modulating oxidative stress situation . 摘要 患有2型糖尿病（T2DM）的患者伴有辅酶Q10（CoQ10）缺乏 , 这将导致一系列并发症。该临床试验研究的目的是评估补充CoQ10对2型糖尿病（T2DM）女性患者的脂联素（A ） , 瘦素（L ） , 8-异前列烷 , 丙二醛（MDA ） , A/L比值的影响。本研究纳入了68名T2DM女性 , 随机分为药物组（n = 34）和安慰剂组（n = 34 ） , 每天服用100mg辅酶Q10和100mg醋酸纤维素 , 共12周。在开始时和干预后对观察指标进行测量。干预后药物组患者的脂联素（p = .001）和A/L比（p = .001）的血清值增加 , 瘦素（p = .041 ） , MDA（p = .023 ） , 8-异前列烷（p = .004）显著下降。本研究表明补充CoQ10对T2DM女性有效 , 可提高脂联素和A/L比值 , 减少瘦素 , MDA和8-异前列烷 , 从而改善胰岛素抵抗 , 调节氧化应激状态
In conclusion , polyphenols can successfully reduce HbA1c in T2DM without any intervention at glycemia , and could contribute to the prevention of diabetes complications
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 .