Evolution of the lipid trial protocol of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review Effects of Probiotic and Prebiotic Supplementation on Leptin, Adiponectin, and Glycemic Parameters in Non-alcoholic Fatty Liver Disease: A Randomized Clinical Trial Dietary fiber, glycemic index, glycemic load and renal cell carcinoma risk. Sitagliptin added to treatment with ongoing pioglitazone for up to 52 weeks improves glycemic control in Japanese patients with type 2 diabetes Sitagliptin added to voglibose monotherapy improves glycemic control in patients with type 2 diabetes Comparison of orlistat treatment and placebo in obese type 2 diabetic patients Full-mouth disinfection as a therapeutic protocol for type-2 diabetic subjects with chronic periodontitis: twelve-month clinical outcomes: a randomized controlled clinical trial. Effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor-1 and fibrinogen in hyperlipidaemic patients. Microvascular endothelial function in subjects with Type 2 diabetes and the effect of lipid-lowering therapy. Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE). N-3 fatty acid supplementation decreases plasma homocysteine in diabetic dyslipidemia treated with statin-fibrate combination. Effect of multi-strain probiotics (multi-strain microbial cell preparation) on glycemic control and other diabetes-related outcomes in people with type 2 diabetes: a randomized controlled trial Effects of vitamin D-fortified low fat yogurt on glycemic status, anthropometric indexes, inflammation, and bone turnover in diabetic postmenopausal women: A randomised controlled clinical trial. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Dietary fiber, whole grains, carbohydrate, glycemic index, and glycemic load in relation to risk of prostate cancer Glycemic control improvement through treatment of depression using antidepressant drugs in patients with diabetes mellitus type 1. Effects of high performance inulin supplementation on glycemic status and lipid profile in women with type 2 diabetes: a randomized, placebo-controlled clinical trial. Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. Phase 3 trials suggest ways to improve current hematologic cancer therapies. Atorvastatin versus Four Statin–Fibrate Combinations in Patients with Familial Combined Hyperlipidaemia Treatment for 6 months with fish oil-derived n-3 polyunsaturated fatty acids has neutral effects on glycemic control but improves dyslipidemia in type 2 diabetic patients with abdominal obesity: a randomized, double-blind, placebo-controlled trial Efficacy of Lactobacillus casei Shirota for patients with irritable bowel syndrome
The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) lipid trial aims to test whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) plus a fibrate is more efficacious in reducing cardiovascular events than a statin plus placebo in patients with type 2 diabetes mellitus with defined glycemic control . This is a blinded component in a 5,518-patient subset of the ACCORD cohort . These participants were r and omized to either be ( 1 ) treated with simvastatin ( titrated to 40 mg/day if necessary to achieve a goal low-density lipoprotein [ LDL ] cholesterol level of < 2.59 mmol/L [ 100 mg/dL ] ) plus placebo or ( 2 ) treated to the same goal LDL cholesterol level with the statin plus active fenofibrate 160 mg/day or its bioequivalent ( or 54 mg/day if the estimated glomerular filtration rate ranges from 30 to < 50 mL/min per 1.73 m2 ) . Setting an upper limit of LDL cholesterol qualifying for r and omization excluded patients who would not likely achieve the LDL cholesterol goal . Recruitment for ACCORD began in January 2001 , and follow-up is scheduled to end in June 2009 . Since recruitment began , several clinical trials and consensus statements have been published that led to changes in the details of the lipid treatment algorithm and protocol . This report describes the design of the lipid protocol and modifications to the protocol during the course of the study in response to and in anticipation of these developments . The current protocol is design ed to provide an ethically justifiable test of combined statin plus fibrate treatment consistent with the highest level of safety and lipid treatment st and ards of care Background Diabetic retinopathy ( DR ) is a common microvascular complication of diabetes mellitus , and more than 75 % of patients who have had diabetes for more than 20 years will have some degree of DR . This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age . The current mainstay of treatment is laser photocoagulation , which causes impairment of vision and discomfort to patients . Thus , finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable . Objective To assess the efficacy and safety of the drugs in the statin and /or fibrate groups for the prevention and treatment of DR . Methods In this systematic review , we will select r and omized controlled trials of fibrates or statins used for the treatment or prevention of DR . Our search strategy will include free text terms and controlled vocabulary ( eg , MeSH , Emtree ) for , “ diabetic retinopathy ” , “ statins ” , “ fibrates ” , “ hypolipidemic agents ” , and for drugs from both groups . Data bases that will be used include Medical Literature Analysis and Retrieval System/ PubMed , Embase , Cochrane Central Register of Controlled Trials , Latin American and Caribbean Center on Health Sciences Information , Clinical trials.gov , World Health Organization International Clinical Trials Registry Platform , and OpenGrey , and we will not have language or date limits . Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration ’s tool . We will report structured summaries of the included studies and , if possible , conduct meta-analyses . Results This is a protocol for a systematic review , therefore results are not available . We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion . Conclusions Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients . Both macrovascular and microvascular events in diabetic patients appear to have a common pathway , starting with endothelial injury . Thus , prevention and treatment of microvascular events may benefit from the same interventions . In the review for which we have written this protocol , we will assess whether the use of lipid-lowering oral drugs of the statin and /or fibrate groups may prevent and /or retard progression of DR , with the added benefit of preserving visual acuity . Trial Registration PROSPERO BACKGROUND According to previous studies , probiotic and prebiotic supplementation have desirable effects on glycemic parameters . Thus far , the effect of supplementation on the glycemic parameters and adipokines in non-alcoholic fatty liver disease ( NAFLD ) has not been assessed . Therefore , the aim of this study was to determine the effects of supplementation with probiotic and prebiotic on adiokines and glycemic parameters in the patients with NAFLD . METHODS In the present r and omized , double-blind , placebo-controlled trial , 89 patients with NAFLD were r and omly divided into three groups to receive one probiotic capsule + 16 g/d maltodextrin ( probiotic group ) or 16 g/d oligofructose powder + one placebo capsule ( prebiotic group ) , and one placebo capsule + 16 g/d maltodextrin ( control group ) for 12 weeks . All the subjects in the study were advised to follow the weight loss diet and physical activity recommendations during the intervention . Fasting blood sample s were taken at baseline and after the intervention to measure leptin , adiponectin , insulin , and fasting blood sugar . RESULTS At the end of the study , serum concentrations of leptin , insulin , and HOMA-IR decreased significantly in the probiotic and prebiotic groups compared with the control group . Despite the changes within the groups , serum concentrations of adiponectin did not change significantly between the three groups . Also , fasting blood sugar did not change between the groups , but decreased in the prebiotic group . Quantitative insulin-sensitivity check index ( QUICKI ) increased significantly in probiotic and prebiotic groups compared with the control group . CONCLUSION Probiotic and prebiotic supplementation along with lifestyle intervention has a favorable impact on glycemic parameters and leptin levels compared with lifestyle intervention alone Several epidemiological studies have investigated the potential association between dietary fiber , glycemic index ( GI ) or glycemic load ( GL ) , and renal cell carcinoma ( RCC ) risk with inconsistent results . The aim of this study was to systematic ally evaluate this issue with a meta- analysis approach . A comprehensive literature search up to March 2018 was performed in PubMed and Web of Science data bases . Summary relative risks ( RRs ) and 95 % confidence intervals ( CIs ) were estimated with a r and om-effects model . Twelve studies were finally included in this study ( eight for fiber analysis , five for GI and five for GL ) . A significant positive association was observed between GI and the risk of RCC ( summary RR 1.16 , 95 % CI 1.02 - 1.32 ) , and no significant heterogeneity was detected among studies ( I2 = 22.8 % , P = 0.262 ) . A significant inverse association was found between fiber intake and the risk of RCC ( summary RR 0.82 , 95 % CI 0.72 - 0.92 ) , and no significant heterogeneity was observed across studies ( I2 = 27.6 % , P = 0.218 ) . GL was not significantly associated with RCC risk ( summary RR 1.14 , 95 % CI 0.81 - 1.60 ) , and significant heterogeneity was found across studies ( I2 = 78.6 % , P < 0.001 ) . In conclusion , this systematic review and meta- analysis suggests that dietary GI and fiber may be associated with the risk of RCC . Further large prospect i ve cohort studies are still warranted to confirm our preliminary findings Abstract Aims / Introduction : Patients with type 2 diabetes mellitus often require treatment with more than one oral antihyperglycemic agent to achieve their glycemic goal . The present study was carried out to assess the efficacy and safety of sitagliptin as add‐on therapy in Japanese patients with type 2 diabetes mellitus inadequately controlled ( HbA1c ≥ 6.9 % and < 10.4 % ) on pioglitazone monotherapy ( 15–45 mg/day ) . Material s and Methods : In the initial 12‐week , double‐blind treatment period , patients were r and omized ( 1:1 ) to sitagliptin 50 mg/day ( n = 66 ) or placebo ( n = 68 ) , followed by a 40‐week open‐label treatment period in which all patients received sitagliptin 50 mg/day that could have been increased to 100 mg/day for patients meeting predefined glycemic parameters . Results : After 12 weeks , mean changes from baseline in HbA1c ( the primary end‐point ) , fasting plasma glucose and 2‐h post‐meal glucose were −0.8 % , −0.9 mmol/L and −2.7 mmol/L , respectively , in the sitagliptin group compared with placebo ( all P < 0.001 ) . The incidence of adverse experiences during the double‐blind treatment period was similar in both treatment groups , and the incidences of hypoglycemia and gastrointestinal adverse experiences were low . In the open‐label period , improvements in glycemic parameters with sitagliptin treatment were maintained and sitagliptin was generally well tolerated . Conclusions : Sitagliptin as add‐on therapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus inadequately controlled on pioglitazone monotherapy . This trial was registered with Clinical Trials.gov ( no. NCT00372060 ) . ( J Diabetes Invest , doi : 10.1111/j.2040‐1124.2011.00120.x , 2011 Abstract Aims / Introduction Type 2 diabetes mellitus is a progressive disease that frequently requires patients to use more than one oral antihyperglycemic agent to achieve adequate glycemic control . The present multicenter , r and omized study assessed the efficacy and safety of the addition of sitagliptin to ongoing voglibose monotherapy ( 0.2–0.3 mg three times daily ) in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control ( glycated hemoglobin ≥6.9 % and < 10.5 % ) . Material s and Methods The present study had an initial 12‐week , double‐blind treatment period in which patients were r and omized ( 1:1 ) to sitagliptin 50 mg/day ( n = 70 )  or placebo ( n = 63 ) , followed by a 40‐week , open‐label treatment period during which all patients received sitagliptin 50 mg/day , that could have been increased to 100 mg/day for patients meeting predefined glycemic criteria . Results After 12 weeks , treatment with sitagliptin result ed in placebo‐subtracted mean changes from baseline in glycated hemoglobin ( the primary end‐point ) , fasting plasma glucose and 2‐h postmeal glucose of –0.9 % , –22.5 mg/dL and –51.3 mg/dL , respectively ( all , P < 0.001 ) . During the double‐blind period , adverse experiences were reported with similar frequency in both treatment groups , and the occurrences of hypoglycemia and gastrointestinal adverse experiences were low . In the open‐label period , sustained improvements in glycemic parameters were observed with sitagliptin treatment , and sitagliptin was generally well tolerated . Conclusions Sitagliptin added on to ongoing voglibose monotherapy provided significant improvements in glycemic parameters and was well tolerated in Japanese patients with type 2 diabetes mellitus who had inadequate glycemic control . This trial was registered with Clinical Trails.gov ( no. NCT00837577 ) Aim : To evaluate the effects of 1-year treatment with orlistat compared with placebo on different inflammatory parameters in type 2 obese diabetic patients . Material s and methods : Two hundred and fifty-four type 2 diabetic patients were r and omized to take orlistat 120 mg three times a day or placebo for 12 months . We evaluated at baseline and after 3 , 6 , 9 and 12 months : leptin , tumor necrosis factor (TNF)-α , adiponectin ( ADN ) , vaspin and high-sensitivity C-reactive protein ( HS-CRP ) , body weight , waist circumference , body mass index ( BMI ) , lipid profile , glycemic profile , fasting plasma insulin ( FPI ) and homeostasis model assessment insulin resistance index ( HOMA-IR ) . Results : Regarding inflammatory parameters , there was a significant improvement of ADN and TNF-α , and a faster decrease of leptin and HS-CRP in the orlistat group compared with the control group . We also recorded a significant reduction of body weight and BMI with orlistat , but not with placebo . A faster improvement of glycemic profile and FPI was obtained with orlistat compared with the controls . Also , there was a significant reduction of lipid profile  with orlistat , not reached with placebo . Conclusions : Orlistat was more effective than placebo in ameliorating inflammatory parameters such as ADN and TNF-α , and anthropometric parameters AIM The aim of this r and omized controlled clinical trial was to evaluate the clinical effects of chlorhexidine ( CHX ) application in a full-mouth disinfection ( FMD ) protocol in poorly controlled type-2 diabetic subjects with generalized chronic periodontitis . MATERIAL AND METHODS Thirty-eight subjects were r and omly assigned into FMD group ( n=19 ) : full-mouth scaling and root planing ( FMSRP ) within 24 h + local application of CHX gel + CHX rinses for 60 days or Control group ( n = 19 ) : FMSRP within 24 h + local application of placebo gel + placebo rinses for 60 days . Clinical parameters , glycated haemoglobin and fasting plasma glucose were assessed at baseline , 3 , 6 and 12 months post-therapies . RESULTS All clinical parameters improved significantly at 3 , 6 and 12 months post-therapies for both groups ( p < 0.05 ) . There were no significant differences between groups for any clinical parameters , and glycemic condition at any time-point ( p > 0.05 ) . CONCLUSIONS The treatments did not differ with respect to clinical parameters , including the primary outcome variable ( i.e. changes in clinical attachment level in deep pockets ) , for up to 12 months post-treatments Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects . A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent . We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator ( t-PA ) , plasminogen activator inhibitor-1 ( PAI-1 ) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen . Although both fibrates effectively lowered triglyceride and cholesterol levels , no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment . However , both fibrates influenced plasma fibrinogen levels , albeit in a different way . Fibrinogen antigen levels were elevated by 17.6 % ( p < 0.05 ) and 24.3 % ( p < 0.001 ) with gemfibrozil after six and twelve weeks , respectively , whereas with ciprofibrate there was no effect . Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point , no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment . However , after twelve weeks , gemfibrozil enhanced functional fibrinogen levels by 7.2 % ( p < 0.05 ) as assessed by the Clauss mechanical assay , but decreased functional fibrinogen levels by 12.5 % ( p < 0.0001 ) when a Clauss assay based on turbidity was used . After six or twelve weeks of ciprofibrate treatment , functional fibrinogen levels were decreased by 10.1 % ( p < 0.001 ) and 10.5 % ( p < 0.0001 ) , respectively on the basis of Clauss mechanical and by 14.2 % ( p < 0.001 ) and 28.2 % ( p < 0.0001 ) , respectively with the Clauss turbidimetric assay . A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen ( determined by either of the two Clauss assays ) to fibrinogen antigen . Taken together , our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates , by differences in treatment period and /or by the different outcomes of various assay systems . Interestingly , the two fibrates tested both reduced the functionality of fibrinogen AIMS Abnormalities of microvascular and endothelial function are present in subjects with Type 2 diabetes . Although statin therapy improves cardiovascular risk in diabetes , dyslipidaemia in diabetes may be more responsive to combined statin and fibrate therapy . We examined the effect of cerivastatin and fenofibrate on microvascular function in subjects with Type 2 diabetes with no clinical evidence of cardiovascular disease and near normal lipid levels . METHODS Age- , sex- , lipid- and blood pressure-matched subjects with Type 2 diabetes were r and omized in double-blind fashion to one of four treatment groups : group 1 placebo/placebo ( n=12 ) , group 2 fenofibrate/placebo ( n=10 ) , group 3 cerivastatin/placebo ( n=20 ) and group 4 cerivastatin/fenofibrate ( n=11 ) . The subjects were recruited from the Lipid in Diabetes Study .  Microvascular function was assessed by skin blood flow response to iontophoresis of acetylcholine and sodium nitroprusside and by skin maximum hyperaemia to local heating . Measurements were carried out at baseline and 3 months later . RESULTS Although all lipid parameters improved in groups 2 - 4 after 3 months ' therapy , no difference was detected in skin blood flow to iontophoresis or maximum hyperaemia in any of the groups . Highly sensitive c-reactive protein ( Hs-CRP ) did not change with therapy . CONCLUSIONS In conclusion , we were unable to demonstrate any improvement in microvascular endothelial function in non-hyperlipidaemic Type 2 diabetic subjects treated with single or combination lipid-lowering therapy Diabetic retinopathy ( DR ) is a major microvascular complication of diabetes mellitus . The Action to Control Cardiovascular Risk in Diabetes Eye Study ( ACCORD-EYE ) , a prospect i ve study of a subset of patients in the r and omized controlled clinical ACCORD trial , is being conducted at enrollment and after 4 years of follow-up to assess the progression of DR with st and ardized comprehensive eye exams and fundus photography of 7 st and ard stereoscopic fields . This study aims to assess the effects of the ACCORD medical treatment strategies of tight control of glycemia and blood pressure and management of dyslipidemia on the course of DR in patients with type 2 diabetes . Photographs will be evaluated at a central ized location using the modified Early Treatment Diabetic Retinopathy Study ( ETDRS ) classification . The primary outcome of ACCORD-EYE , which will measure the development and progression of DR , is a composite of ( 1 ) progression of DR ( > or = 3 steps on the ETDRS scale ) , ( 2 ) photocoagulation for DR , or ( 3 ) vitrectomy for DR . Specifically , the following questions will be addressed : ( 1 ) Does a therapeutic strategy targeting a glycosylated hemoglobin ( HbA(1c ) ) level < 6.0 % reduce development and progression of DR more than one targeting an HbA(1c ) level of 7.0%-7.9 % ( target median level , 7.5 % ) ? ( 2 ) In the context of good glycemic control , does a strategy using a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels and a statin to maintain the level of low-density lipoprotein ( LDL ) cholesterol at < 2.59 mmol/L ( 100 mg/dL ) reduce development and progression of DR compared with one using placebo and a statin to treat LDL cholesterol ? ( 3 ) In the context of good glycemic control , does a strategy targeting a systolic blood pressure level < 120 mm Hg reduce development and progression of DR compared with one targeting a level < 140 mm Hg ? Secondary outcome variables include various levels of loss of visual acuity at 4 years versus baseline , cataract extraction , and the development or progression of diabetic macular edema . Methods to measure DR progression have been incorporated into ACCORD , and complete baseline data have been collected on 3,537 participants . These data will provide valuable information regarding the effects of medical treatment on the prevention and progression of DR The aim of this study was to study the effect of adding polyunsaturated fatty acid ( PUFA ) n-3 or placebo ( containing oleic acid ) to a combined statin-fibrate treatment on plasma lipoproteins , lipoperoxidation , glucose homeostasis , total homocysteine ( tHcy ) and microalbuminuria ( MA ) in patients with diabetic dyslipidemia ( DDL ) . Twenty-four patients , who did not fulfill the recommended target lipid values with combined hypolipidemic therapy ( pravastatin 20 mg+micronized fenofibrate 200 mg daily ) , were supplemented with 3.6 g PUFA n-3 daily for 3 months or placebo ( olive oil ) for the next 3 months . The concentrations of plasma lipids , fatty acid ( FA ) profiles of phosphatidylcholine ( PC ) , cholesteryl esters ( CE ) and triglycerides ( TG ) , tHcy levels , concentrations of conjugated dienes ( CD ) in low-density lipoprotein ( LDL ) , and MA were determined in baseline state , after the PUFA n-3 and placebo treatment period . Supplementation with PUFA n-3 led to a significant decrease in plasma tHcy ( -29 % , P < .01 ) and TG ( -28 % , P < .05 ) levels , as well as to a significant decrease in MA ( -24 % , P < .05 ) . The decrease in MA correlated significantly with the increase in total PUFA n-3 ( r = -.509 , P < or = .05 ) and docosahexaenoic acid ( r = -.52 , P < .01 ) in TG . The concentrations of CD in LDL increased significantly ( + 15 % , P < .05 ) . The supplementation with PUFA n-3 to the combined statin-fibrate treatment in patients with DDL decreased the TG and tHcy levels as well as MA . It could lead to decreased risk of atherothrombosis and delay of diabetic nephropathy onset and progression Aim Evidence of a possible connection between gut microbiota and several physiological processes linked to type 2 diabetes is increasing . However , the effect of multi-strain probiotics in people with type 2 diabetes remains unclear . This study investigated the effect of multi-strain microbial cell preparation — also refers to multi-strain probiotics — on glycemic control and other diabetes-related outcomes in people with type 2 diabetes . Design A r and omized , double-blind , parallel-group , controlled clinical trial . Setting Diabetes clinic of a teaching hospital in Kuala Lumpur , Malaysia . Participants A total of 136 participants with type 2 diabetes , aged 30–70 years , were recruited and r and omly assigned to receive either probiotics ( n = 68 ) or placebo ( n = 68 ) for 12 weeks . Outcomes Primary outcomes were glycemic control-related parameters , and secondary outcomes were anthropomorphic variables , lipid profile , blood pressure and high-sensitivity C-reactive protein . The Lactobacillus and Bifidobacterium quantities were measured before and after intervention as an indicator of successful passage of the supplement through gastrointestinal tract . Statistical analysis Intention-to-treat ( ITT ) analysis was performed on all participants , while per- protocol ( PP ) analysis was performed on those participants who had successfully completed the trial with good compliance rate . Results With respect to primary outcomes , glycated hemoglobin decreased by 0.14 % in the probiotics and increased by 0.02 % in the placebo group in PP analysis ( p < 0.05 , small effect size of 0.050 ) , while these changes were not significant in ITT analysis . Fasting insulin increased by 1.8 µU/mL in placebo group and decreased by 2.9 µU/mL in probiotics group in PP analysis . These changes were significant between groups at both analyses ( p < 0.05 , medium effect size of 0.062 in PP analysis and small effect size of 0.033 in ITT analysis ) . Secondary outcomes did not change  significantly . Probiotics successfully passed through the gastrointestinal tract . Conclusion Probiotics modestly improved HbA1c and fasting insulin in people with type 2 diabetes BACKGROUND & AIMS Low levels of serum 25-hydroxy vitamin D ( 25(OH)D ) are common in type 2 diabetic patients and cause several complications particularly , in postmenopausal women due to their senile and physiological conditions . This study aim ed to assess the effects of vitamin D-fortified low fat yogurt on glycemic status , anthropometric indexes , inflammation , and bone turnover in diabetic postmenopausal women . METHODS In a r and omized , placebo-controlled , double-blind parallel-group clinical trial , 59 postmenopausal women with type 2 diabetes received fortified yogurt ( FY ; 2000 IU vitamin D in 100 g/day ) or plain yogurt  ( PY ) for 12 weeks . Glycemic markers , anthropometric indexes , inflammatory , and bone turnover markers were assessed at baseline and after 12 weeks . RESULTS After intervention , in FY group ( vs PY group ) , were observed : significant increase in serum 25(OH)D and decrease of PTH ( stable values in PY ) ; significant improvement in serum fasting insulin , HOMA-IR , HOMA-B , QUICKI , and no changes in serum fasting glucose and HbA1c ( significant worsening of all indexes in PY ) ; significant improvement in WC , WHR , FM , and no change in weight and BMI ( stable values in PY ) ; significant increase of omentin ( stable in PY ) and decrease of sNTX ( significant increase in PY ) . Final values of glycemic markers ( except HbA1c ) , omentin , and bone turnover markers significantly improved in FY group compared to PY group . Regarding final values of serum 25(OH)D in FY group , subjects were classified in insufficient and sufficient categories . Glycemic status improved more significantly in the insufficient rather than sufficient category ; whereas the other parameters had more amelioration in the sufficient category . CONCLUSIONS Daily consumption of 2000 IU vitamin D-fortified yogurt for 12 weeks improved glycemic markers ( except HbA1c ) , anthropometric indexes , inflammation , and bone turnover markers in postmenopausal women with type 2 diabetes . TRIAL REGISTRATION www.i rct .ir ( I RCT 2013110515294N1 ) Most patients with type 2 diabetes mellitus develop cardiovascular disease ( CVD ) , with substantial loss of life expectancy . Nonfatal CVD contributes greatly to excess healthcare costs and decreased quality of life in patients with diabetes . The current epidemic of obesity has raised expectations that CVD associated with type 2 diabetes will become an even greater public health challenge . Despite the importance of this health problem , there is a lack of definitive data on the effects of the intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes . The Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial is a r and omized , multicenter , double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for CVD events because of existing CVD or additional risk factors . ACCORD is testing the effects of 3 medical treatment strategies to reduce CVD morbidity and mortality . All participants are in the glycemia trial , which is testing the hypothesis that a therapeutic strategy that targets a glycosylated hemoglobin ( HbA1c ) level of < 6.0 % will reduce the rate of CVD events more than a strategy that targets an HbA1c level of 7.0%-7.9 % . The lipid trial includes 5,518 of the participants , who receive either fenofibrate or placebo in a double-masked fashion to test the hypothesis of whether , in the context of good glycemic control , a therapeutic strategy that uses a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels together with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor ( statin ) to lower low-density lipoprotein cholesterol will reduce the rate of CVD events compared with a strategy that uses a statin plus a placebo . The blood pressure trial includes the remaining 4,733 participants and tests the hypothesis that a therapeutic strategy that targets a systolic blood pressure of < 120 mm Hg in the context of good glycemic control will reduce the rate of CVD events compared with a strategy that targets a systolic blood pressure of < 140 mm Hg . The primary outcome measure for all 3 research questions is the first occurrence of a major CVD event , specifically nonfatal myocardial infa rct ion , nonfatal stroke , or cardiovascular death . Upon the expected completion of participant follow-up in 2009 , the ACCORD trial should document for the first time the benefits and risks of intensive glucose control , intensive blood pressure control , and the combination of fibrate and statin drugs in managing blood lipids in high-risk patients with type 2 diabetes Background The relationships between dietary fiber , whole grains , carbohydrate , glycemic index ( GI ) , glycemic load ( GL ) , and prostate cancer risk are unclear . We conducted a systematic review and meta- analysis to investigate these associations . Methods Relevant studies were identified by a search of PubMed data base and EMBASE data base up to April 2015 . A r and om effects model was used to calculate the summary relative risks ( RRs ) and their corresponding 95 % confidence intervals ( CIs ) . Results Twenty-seven epidemiological studies ( 18 case – control studies and nine cohort studies ) were included in the final analysis .  The pooled RRs of prostate cancer were 0.94 ( 95 % CI 0.85–1.05 , P=0.285 ) , 1.13 ( 95 % CI 0.98–1.30 , P=0.095 ) , 0.96 ( 95 % CI 0.81–1.14 , P=0.672 ) , 1.06 ( 95 % CI 0.96–1.18 , P=0.254 ) , and 1.04 ( 95 % CI 0.91–1.18 , P=0.590 ) for dietary fiber , whole grains , carbohydrate , GI , and GL , respectively . There was no evidence of significant publication bias based on the Begg ’s test and Egger ’s test . Conclusion The findings of this meta- analysis indicate that , based on available information , dietary fiber , whole grains , carbohydrate , GI , and GL are not associated with the risk of prostate cancer OBJECTIVE Depression is a common disorder among diabetic patients and affects negatively the treatment of their basic disease . The aim of the study was to assess , whether antidepressant medication could positively influence glycemic control of diabetes type 1 in depressive or anxious patients . METHODS A six-month , double-blinded , r and omized , placebo-controlled study was performed to investigate the reaction of type 1diabetic patients ( n=21 ) to treatment of depression and anxiety symptoms using antidepressant drug sertraline . The patients were given sertraline ( 100 mg/day ) or placebo . The evolution of mental change was assessed using Zung Self-Rating Depression Scale ( SDS ) , Hamilton Anxiety Rating Scale ( HAMA ) and Hamilton Depression Rating Scale ( HAMD ) along with development of somatic parameters commonly assessed in diabetic patients , especially glycosylated hemoglobin , insulin dose and body weight . The level of active substance in serum of the patients was also measured . RESULTS Mental state improved at the level of statistical significance of p<0.001 in both patients using antidepressant and placebo . From somatic parameters , body weight and systolic blood pressure increased statistically significantly also in both groups of patients . CONCLUSIONS The mental state of most patients who successfully completed the study improved regardless of the fact if they were using antidepressant or placebo . No statistically significant connections between the mental and somatic changes were found . This finding points out to the placebo effect of the medication , to the importance of a contact with patients , but also to the need to concentrate on their mental state BACKGROUND Type 2 diabetes mellitus , as a noncommunicable disease , is the main public health challenge in the 21st century . The prevalence of diabetes mellitus adjusted for the world population in Iran was 8 % until the year 2010.Lipid levels are considered as important parameters to be evaluated , as high serum lipid levels are often reported as a complication in patients with diabetes mellitus . It is cl aim ed that functional foods may improve complications of diabetes mellitus , so this study was design ed to evaluate the effects of high performance inulin on glycemic status and lipid profile of women with type 2 diabetes . METHODS The study was a r and omized controlled clinical trial . Forty-nine type 2 diabetic females ( fiber intake < 30g/d , 25 < BMI < 35 kg/m2 ) were divided into two groups . Patients in the intervention group ( n=24 ) received 10g/d inulin and patients in the control group ( n=25 ) received 10g/d maltodextrin for 8 weeks .  Glycemic status and lipid profile indices were measured pre and post intervention . Data were analyzed using SPSS software ( verision11.5 ) . Paired , unpaired t-test and ANCOVA were used to compare quantitative variables . RESULTS Supplementation with inulin caused a significant reduction in FBS ( 8.50 % ) , HbA1c ( 10.40 % ) , total cholesterol ( 12.90 % ) , triglyceride ( 23.60 % ) , LDL-c ( 35.30 % ) , LDL-c/HDL-c ratio ( 16.25 % ) and TC/HDL-c ratio ( 25.20 % ) and increased HDL-c ( 19.90 % ) . The changes for the control group parameters were not significant at the end of study . CONCLUSION Inulin may help to control diabetes and its complications via improving glycemic and lipid parameters IMPORTANCE Persons with type 2 diabetes mellitus ( T2DM ) are at increased risk for decline in cognitive function , reduced brain volume , and increased white matter lesions in the brain . Poor control of blood pressure ( BP ) and lipid levels are risk factors for T2DM-related cognitive decline , but the effect of intensive treatment on brain function and structure is unknown . OBJECTIVE To examine whether intensive therapy for hypertension and combination therapy with a statin plus a fibrate reduces the risk of decline in cognitive function and total brain volume ( TBV ) in patients with T2DM . DESIGN , SETTING , AND PARTICIPANTS A North American multicenter clinical trial including 2977 participants without baseline clinical evidence of cognitive impairment or dementia and with hemoglobin A1c ( HbA1c ) levels less than 7.5 % r and omized to a systolic BP goal of less than 120 vs less than 140 mm Hg ( n = 1439 ) or to a fibrate vs placebo in patients with low-density lipoprotein cholesterol levels less than 100 mg/dL ( n = 1538 ) . Participants were recruited from August 1 , 2003 , through October 31 , 2005 , with the final follow-up visit by June 30 , 2009 . MAIN OUTCOME MEASURES Cognition was assessed at baseline and 20 and 40 months . A subset of 503 participants underwent baseline and 40-month brain magnetic resonance imaging to assess for change in TBV and other structural measures of brain health . RESULTS Baseline mean HbA1c level was 8.3 % ; mean age , 62 years ; and mean duration of T2DM , 10 years . At 40 months , no differences in cognitive function were found in the intensive BP-lowering trial or in the fibrate trial . At 40 months , TBV had declined more in the intensive vs st and ard BP-lowering group ( difference , -4.4 [ 95 % CI , -7.8 to -1.1 ] cm(3 ) ; P = .01 ) . Fibrate therapy had no effect on TBV compared with placebo . CONCLUSIONS AND RELEVANCE In participants with long-st and ing T2DM and at high risk for cardiovascular events , intensive BP control and fibrate therapy in the presence of controlled low-density lipoprotein cholesterol levels did not produce a measurable effect on cognitive decline at 40 months of follow-up . Intensive BP control was associated with greater decline in TBV at 40 months relative to st and ard therapy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000620 be determined . That may change by early in the next decade , when results are expected from 3 large trials of combination therapies . Brown is leading the Niacin Plus Statin to Prevent Vascular Events ( AIM HIGH ) trial , r and omizing 6600 patients with established vascular disease and atherogenic dyslipidemia to either simvastatin or an extendedrelease combination therapy of niacin and simvastatin . These patients will be followed up for a median of 4 years to see if the combination therapy delays the time to a first major cardiovascular disease event . Another trial is the HPS2-THRIVE ( Treatment of HDL to Reduce the Incidence of Vascular Events ) study of 20 000 patients in the United Kingdom , China , and Sc and inavia to determine if combining niacin with a new drug ( MK-0524A ) that minimizes flushing can reduce cardiovascular disease risk in patients already effectively treating their low-density lipoprotein cholesterol ( LDL-C ) levels . The study is sponsored by Merck & Co Inc ( Whitehouse Station , NJ ) . The third study is an arm of the Action to Control Cardiovascular Risk in Diabetes ( ACCORD ) trial . A portion of the 10 251 study participants with type 2 diabetes mellitus are being followed up to determine if , in the context of good glycemic control , raising HDL-C and lowering triglyceride and LDL-C levels with a combination of a fibrate and a statin reduces the rate of cardiovascular events compared with statin therapy only for treatment of Background Statin – fibrate combinations are very effective in the treatment of familial combined hyperlipidaemia ( FCHL ) . Nonetheless , they have not been extensively used because of the fear of side effects . Thus , a therapeutic alternative is required for this lipid disorder . Objective To compare the long-term ( one-year ) efficacy of atorvastatin monotherapy with those of four statin – fibrate combinations in 675 FCHL patients . Methods Patients were r and omly assigned to atorvastatin monotherapy ( A 20 mg/day ) n=134 , or pravastatin ( P 20 mg/day)+gemfibrozil ( G 1200 mg/day ) n=135 , simvastatin ( S 20 mg/day)+G ( 1200 mg/day ) n=137 , P ( 20 mg/day)+ciciprofibrate ( C 100 mg/day ) n=135 , and S ( 20 mg/day)+C ( 100 mg/day ) n=134 . Results Twelve patients on statin – fibrate combinations were withdrawn from the study because of side effects : Three because of CK elevation , two because of myalgia and seven due to increase in serum transaminase levels . One patient on A was withdrawn because of persistent epigastric discomfort .  Atorvastatin  reduced low density lipoprotein cholesterol and apoprotein B more than all four combinations ( −45 % vs. maximum −40 % of S+C , and −39 % vs. maximum −32 % of the same combination , respectively , P < 0.001 for both ) , but had a lesser effect on triglycerides ( −38 % vs. maximum −53 % of S+C , P=0.0002 ) and high density lipoprotein cholesterol ( 6 % vs. maximum 21 % of S+G , P=0.0003 ) . The effect of A on plasma fibrinogen was analogous to that of G combinations ( −8 % vs. −9 % of P+G and −11 % of S+G , P = NS vs. baseline and among each other ) and inferior to that of the ciprofibrate combinations ( −8 % vs. −24 % of P+C , P=0.0002 and −26 % S+C , P=0.0001 ) . A had a lower treatment cost and better patient compliance , P=0.04 vs. C combinations and P=0.02 vs. G combinations . Conclusions The data suggest that statin – fibrate combinations have a beneficial effect on all lipid parameters . Atorvastatin monotherapy has a better effect on LDL-C and apoprotein B than statin – fibrate combinations , but a lesser effect on HDL-C , TG and in the case of ciprofibrate combinations , fibrinogen . The clinical significance of these findings should be tested in a large , long-term survival study Purpose This study aim ed to determine the effects of fish oil-derived n-3 PUFA on glycemic control and lipid profiles in type 2 diabetic patients with abdominal obesity . Methods In a r and omized , double-blind , placebo-controlled trial , 100 type 2 diabetic patients with abdominal obesity were r and omized into two groups including 4 g/day of fish oil ( 2.4 g n-3 PUFA ) or placebo ( corn oil ) for 6 months . Serum fatty acid , body composition , as well as markers of glucose regulation and lipid parameters were measured before and after intervention . Results Thirty-five men and 64 women aged 65.4 ± 5.3 years completed the intervention . Although body composition was unchanged , serum EPA and DHA were higher in the fish oil group than those in the placebo group ( P < 0.001 and P < 0.001 , respectively ) . Serum triglyceride ( TG ) decreased ( P = 0.007 ) , whereas high-density lipoprotein cholesterol ( HDL-C ) increased ( P = 0.006 ) in the fish oil group compared with the placebo group after 6 months . Serum total cholesterol , low-density lipoprotein cholesterol ( LDL-C ) , the ratio of LDL-C to HDL-C , and glycemic control ( measured by serum glucose , glycated hemoglobin , insulin , and homeostasis model assessment –insulin resistance ) were not significantly different between the two groups after 6 months . Conclusions This study showed that 6 months of fish oil supplement had no statistically significant effects on glycemic control , but improved TG and HDL-C in type 2 diabetic patients with abdominal obesity . Trial registration Chictr.org ChiCTR-TRC-14005084 Background and aims Meta-analyses point to a modest but significant effect of probiotics on symptoms in irritable bowel syndrome ( IBS ) . We aim ed to assess the effect of the probiotic Lactobacillus casei Shirota ( LcS ) on symptoms and quality of life in IBS patients in a r and omized , double-blind , placebo-controlled intervention study . Material s and methods IBS patients ( Rome II ) between 18 and 65 years of age were included . The study consisted of an 8-week intervention period in which the participants received probiotic ( LcS ) or placebo twice daily , followed by an 8-week follow-up period . Symptom diaries and quality of life were scored at weeks 0 , 8 and 16 . The primary outcome parameter was a decrease of at least 30 % in a composite mean symptom score ( MSS ) at week 8 on the basis of an intention-to-treat analysis . Results Thirty-nine individuals ( 67 % women ) were included in the probiotic group and 41 individuals ( 71 % women ) were included in the placebo group . After the intervention period , the mean relative improvement did not reach 30 % for MSS or any individual symptom score . After follow-up ( week 16 ) , a mean improvement of at least 30 % was achieved for MSS in the probiotic group , but no significant difference was found between both treatment groups ( mean±SD : 34±7 % ; 13±8 % , P=0.06 ) . Conclusion After probiotic treatment with LcS , no improvement of 30 % in MSS was observed after 8 weeks
Conclusion : This meta‐ analysis has shown that fibrate treatment  significantly decreases fasting plasma glucose , insulin levels , and HOMA‐IR indicating additional clinical therapeutic benefits .
Aims : The aim of this meta‐ analysis of r and omized placebo‐controlled clinical trials was to assess the effect of fibrates on glycemic parameters .