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      A randomised controlled trial of increasing fruit and vegetable intake and how this influences the carotenoid concentration and activities of PON-1 and LCAT in HDL from subjects with type 2 diabetes

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          Abstract

          Background

          High density lipoproteins (HDL) have many cardioprotective roles; however, in subjects with type 2 diabetes (T2D) these cardioprotective properties are diminished. Conversely, increased fruit and vegetable (F&V) intake may reduce cardiovascular disease risk, although direct trial evidence of a mechanism by which this occurs in subjects with T2D is lacking. Therefore, the aim of this study was to examine if increased F&V consumption influenced the carotenoid content and enzymes associated with the antioxidant properties of HDL in subjects with T2D.

          Methods

          Eighty obese subjects with T2D were randomised to a 1- or ≥6-portion/day F&V diet for 8-weeks. Fasting serum was collected pre- and post-intervention. HDL was subfractionated into HDL 2 and HDL 3 by rapid ultracentrifugation. Carotenoids were measured in serum, HDL 2 and HDL 3 by high performance liquid chromatography. The activity of paraoxonase-1 (PON-1) was measured in serum, HDL 2 and HDL 3 by a spectrophotometric assay, while the activity of lecithin cholesterol acyltransferase (LCAT) was measured in serum, HDL 2 and HDL 3 by a fluorometric assay.

          Results

          In the ≥6- vs. 1-portion post-intervention comparisons, carotenoids increased in serum, HDL 2 and particularly HDL 3, (α-carotene, p = 0.008; β-cryptoxanthin, p = 0.042; lutein, p = 0.012; lycopene, p = 0.016), as did the activities of PON-1 and LCAT in HDL 3 (p = 0.006 and 0.044, respectively).

          Conclusion

          To our knowledge, this is the first study in subjects with T2D to demonstrate that increased F&V intake augmented the carotenoid content and influenced enzymes associated with the antioxidant properties of HDL. We suggest that these changes would enhance the cardioprotective properties of this lipoprotein.

          Clinical trial registration

          ISRCTN21676269

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          Most cited references26

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          Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors.

          Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation. To generate reliable reference intervals for plasma malondialdehyde (P-MDA), a reference sample group was established in Funen, Denmark. The group consisted of 213 individuals (107 men, 106 women), ages 20-79 years. P-MDA was measured in EDTA-treated plasma after derivatization by thiobarbituric acid (TBA) and separation on HPLC. UV detection was performed at 532 nm. A reference interval was calculated as recommended by IFCC with REFVAL 3.42. The estimated reference limits (0.025 and 0.975 fractals) for the group were 0.36 and 1.24 mumol/L. The data were analyzed for gender- and age-related differences. Analysis of variance showed no interaction between gender and age, but separate analyses showed an independent effect of gender (P = 0.03), but not of age (P = 0.11). Daily smokers had a slightly higher average concentration of P-MDA than nonsmokers (P = 0.05), and P-MDA correlated with daily exposure to cigarette smoke (r = 0.162; P = 0.03). A positive correlation was also demonstrated between P-MDA and weekly alcohol consumption (r = 0.153; P = 0.03). Within-subject and day-to-day variations of P-MDA indicated that the potential of P-MDA as a biomarker for individuals is questionable. However, on a group basis, the present data support that P-MDA may be a potential biomarker for oxidative stress.
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            Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice.

            Dietary supplementation with nutrients rich in antioxidants is associated with inhibition of atherogenic modifications to LDL, macrophage foam cell formation, and atherosclerosis. Pomegranates are a source of polyphenols and other antioxidants. We analyzed, in healthy male volunteers and in atherosclerotic apolipoprotein E-deficient (E(0)) mice, the effect of pomegranate juice consumption on lipoprotein oxidation, aggregation, and retention; macrophage atherogenicity; platelet aggregation; and atherosclerosis. Potent antioxidative effects of pomegranate juice against lipid peroxidation in whole plasma and in isolated lipoproteins (HDL and LDL) were assessed in humans and in E(0) mice after pomegranate juice consumption for
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              Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

              Background Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Methods Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. Results Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. Conclusions These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition.
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                Author and article information

                Journal
                Cardiovasc Diabetol
                Cardiovasc Diabetol
                Cardiovascular Diabetology
                BioMed Central
                1475-2840
                2014
                14 January 2014
                : 13
                : 16
                Affiliations
                [1 ]Centre for Public Health, Queen’s University Belfast, Pathology Building, Grosvenor Road, Belfast BT12 6BJ, UK
                [2 ]Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast BT12 6BA, UK
                Article
                1475-2840-13-16
                10.1186/1475-2840-13-16
                3898240
                24423117
                2a39a746-abe6-45e0-bad6-7387ee8c9349
                Copyright © 2014 Daniels et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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
                : 19 November 2013
                : 9 January 2014
                Categories
                Original Investigation

                Endocrinology & Diabetes
                paraoxonase-1,lecithin cholesterol acyltransferase,carotenoids,type-2 diabetes,fruit and vegetables,high density lipoprotein

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