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      Effects of a hydroalcoholic extract of Juglans regia (walnut) leaves on blood glucose and major cardiovascular risk factors in type 2 diabetic patients: a double-blind, placebo-controlled clinical trial

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          Abstract

          Background

          We aimed to evaluate the effects of a hydroalcoholic extract of Juglans regia L. leaves on blood glucose level and cardiovascular risk factors in type 2 diabetic patients.

          Methods

          In this randomized, double-blind, placebo-controlled, parallel-group (2 arms) clinical trial, 50 diabetic patients were divided into two groups: treatment group (receive the capsules containing 100 mg  J. regia leaf extract) and control group (receive the capsules containing placebo, microcrystallin cellulose). Baseline participant data were matched between the two arms of the study. We administered the prepared capsules to the patients twice daily for 8 weeks. Blood glucose level, glycosylated hemoglobin (HbA1c) level, body weight, body mass index, blood pressure, lipid profile, serum insulin, and insulin resistance were compared between the two groups before and after the intervention. P < 0.05 was considered significant.

          Results

          After excluding eleven patients, 20 received J. regia leaf extract and 20 patients received placebo. The J. regia leaf extract did not significantly change the blood glucose and insulin resistance condition. However, in this group, body weight, body mass index, and systolic blood pressure significantly decreased compared with the baseline measurements ( P = 0.028, P = 0.030, and P = 0.005, respectively). The lipid profile did not change significantly compared with the baseline measurements. In the control group, postprandial glucose and HbA1c levels significantly decreased after the intervention (P = 0.030 and P = 0.028, respectively). The other variables were not significantly different in this group. At the end of the study, the variables were not significantly different between the two groups.

          Conclusion

          In this double-blind study, 200 mg/d of J. regia leaf extract had no significant effect on blood glucose level and HOMA-IR score in patients with type 2 diabetes. However, the J. regia leaf extract was effective in reducing body weight and blood pressure. An accidental finding of our study was that microcrystalline cellulose, a widely used placebo in clinical trials, led to a reduction in blood glucose level.

          Trial registration

          Iranian Registry of Clinical Trials (IRCT: 138901203180 N2, 2010/6/6); retrospectively registered.

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          Most cited references19

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          The assessment of insulin resistance in man.

          Insulin resistance exists when a normal concentration of insulin produces a less than normal biological response. The ability to measure insulin resistance is important in order to understand the aetiopathology of Type 2 diabetes, to examine the epidemiology and to assess the effects of intervention. We assess and compare methods of measurement and have undertaken a literature review from 1966 to 2001. Quantitative estimates of insulin resistance can be obtained using model assessments, clamps or insulin infusion sensitivity tests. There is considerable variation in the complexity and labour intensity of the various methods. The most well-established methods are the euglycaemic clamp, minimal model assessment and homeostatic model assessment (HOMA). No single test is appropriate under all circumstances. There are a number of well-established tests used to measure insulin resistance: the choice of method depends on the size and type of study to be undertaken. Although the so-called 'gold-standard' test, the euglycaemic clamp, is useful for intensive physiological studies on small numbers of subjects, a simpler tool such as HOMA is more appropriate for large epidemiological studies. It is important to be aware that most techniques measure stimulated insulin resistance whereas HOMA gives an estimate of basal insulin resistance. Caution should be exercised when making comparisons between studies due to variations in infusion protocols, sampling procedures and hormone assays used in different studies.
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            Polyphenols and prevention of cardiovascular diseases.

            Polyphenols are the most abundant dietary antioxidants and research on their role in the prevention of degenerative diseases has developed quickly over these last few years. This paper reviews the recent studies on the prevention of cardiovascular diseases by polyphenols, focusing on human studies. A large number of recent intervention studies have shown that several biomarkers of cardiovascular risk are influenced by the consumption of polyphenol-rich foods. Effects on biomarkers of oxidative stress, lipemia and inflammation appear so far inconclusive. More consistent effects have been observed on endothelial function and haemostasis and support a reduction of risk by polyphenols in agreement with the few epidemiological studies already published. All clinical studies have used foods or beverages containing a mixture of different polyphenols and the exact nature of the most active compounds remains largely unknown. Absorption, metabolism and elimination vary widely between polyphenols. These data on bioavailability should be taken into account to improve the experimental design and the interpretation of the observed effects. Future intervention studies should include a detailed assessment of the bioavailability of polyphenols. Beyond clinical trials carried out with polyphenol-rich foods, more studies with pure polyphenols will also be needed to establish their role in the prevention of cardiovascular diseases.
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              Effects of Walnut Consumption on Endothelial Function in Type 2 Diabetic Subjects

              OBJECTIVE To determine the effects of daily walnut consumption on endothelial function, cardiovascular biomarkers, and anthropometric measures in type 2 diabetic individuals. RESEARCH DESIGN AND METHODS This study was a randomized, controlled, single-blind, crossover trial. Twenty-four participants with type 2 diabetes (mean age 58 years; 14 women and 10 men) were randomly assigned to one of the two possible sequence permutations to receive an ad libitum diet enriched with 56 g (366 kcal) walnuts/day and an ad libitum diet without walnuts for 8 weeks. Subjects underwent endothelial function testing (measured as flow-mediated dilatation [FMD]) and assessment of cardiovascular biomarkers before and after each 8-week treatment phase. The primary outcome measure was the change in FMD after 8 weeks. Secondary outcome measures included changes in plasma lipids, A1C, fasting glucose, insulin sensitivity, and anthropometric measures. RESULTS Endothelial function significantly improved after consumption of a walnut-enriched ad libitum diet compared with that after consumption of an ad libitum diet without walnuts (2.2 ± 1.7 vs. 1.2 ± 1.6%; P = 0.04). The walnut-enriched diet increased fasting serum glucose and lowered serum total cholesterol and LDL cholesterol from baseline (10.0 ± 20.5 mg/dl, P = 0.04; −9.7 ± 14.5 mg/dl, P < 0.01; and −7.7 ± 10 mg/dl, P < 0.01, respectively), although these changes were not significant compared with those for an ad libitum diet without walnuts. There were no significant changes in anthropometric measures, plasma A1C, and insulin sensitivity. CONCLUSIONS A walnut-enriched ad libitum diet improves endothelium-dependent vasodilatation in type 2 diabetic individuals, suggesting a potential reduction in overall cardiac risk.
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                Author and article information

                Contributors
                mprabie@yahoo.com
                zadeh20@gmail.com
                majsaeedi@gmail.com
                doctor_bahar2000@yahoo.com
                zr_akha@yahoo.com
                00981133378789 , kashi_zahra@yahoo.com
                Journal
                BMC Complement Altern Med
                BMC Complement Altern Med
                BMC Complementary and Alternative Medicine
                BioMed Central (London )
                1472-6882
                4 July 2018
                4 July 2018
                2018
                : 18
                : 206
                Affiliations
                [1 ]World Federation of Acupunture-Moxibustion Societies (WFAS), Scientific Studies Institute of Nadali Esmaeili, Acupuncture Center, Sari, Iran
                [2 ]ISNI 0000 0001 2227 0923, GRID grid.411623.3, Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, , Mazandaran University of Medical Sciences, ; Sari, Iran
                [3 ]ISNI 0000 0001 2227 0923, GRID grid.411623.3, Diabetes Research Center, , Mazandaran University of Medical Sciences, ; Sari, Iran
                [4 ]ISNI 0000 0001 2227 0923, GRID grid.411623.3, Traditional and Complementary Medicine Research Center, Addiction Institute, , Mazandaran University of Medical Sciences, ; Sari, Iran
                Author information
                http://orcid.org/0000-0002-4683-1323
                Article
                2268
                10.1186/s12906-018-2268-8
                6031195
                29973195
                14a7738f-eb8e-40fe-a50e-47f55f1b2a43
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 29 March 2018
                : 22 June 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004160, Mazandaran University of Medical Sciences;
                Award ID: CT-P-92-5670
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Complementary & Alternative medicine
                diabetes mellitus,juglans regia,walnut leaves,herbal medicine,weight,blood glucose,blood pressure,cardiovascular,microcrystalline cellulose,avicel

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