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Pistachio consumption modulates DNA oxidation and genes related to telomere maintenance: a crossover randomized clinical trial.

Canudas, S., P. Hernández-Alonso, S. Galié, J. Muralidharan, L. Morell-Azanza, G. Zalba, J. García-Gavilán, A. Martí, J. Salas-Salvadó, M. Bulló, 2019. Pistachio consumption modulates DNA oxidation and genes related to telomere maintenance: a crossover randomized clinical trial. Am J Clin Nutr. 109:1738–1745.

Background: Telomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D), increasing the probability of β cell senescence and leading to reduced cell mass and decreased insulin secretion. Nutrition and lifestyle are known factors modulating the aging process and insulin resistance/secretion, determining the risk of T2D. Objectives: The aim of this study was to evaluate the effects of pistachio intake on telomere length and other cellular aging-related parameters of glucose and insulin metabolism. Methods: Forty-nine prediabetic subjects were included in a randomized crossover clinical trial. Subjects consumed a pistachio supplemented diet (PD, 50 E% [energy percentage] carbohydrates and 33 E% fat, including 57 g pistachios/d) and an isocaloric control diet (CD, 55 E% carbohydrates and 30 E% fat) for 4 mo each, separated by a 2-wk washout period. DNA oxidation was evaluated by DNA damage (via 8- hydroxydeoxyguanosine). Leucocyte telomere length and gene expression related to either oxidation, telomere maintenance or glucose, and insulin metabolism were analyzed by multiplexed quantitative reverse transcriptase-polymerase chain reaction after the dietary intervention. Results: Compared with the CD, the PD reduced oxidative damage to DNA (mean: −3.5%; 95% CI: −8.07%, 1.05%; P = 0.009). Gene expression of 2 telomere-related genes (TERT and WRAP53) was significantly upregulated (164% and 53%) after the PD compared with the CD (P = 0.043 and P = 0.001, respectively). Interestingly, changes in TERT expression were negatively correlated to changes in fasting plasma glucose concentrations and in the homeostatic model assessment of insulin resistance. Conclusions: Chronic pistachio consumption reduces oxidative damage to DNA and increases the gene expression of some telomere-associated genes. Lessening oxidative damage to DNA and telomerase expression through diet may represent an intriguing way to promote healthspan in humans, reversing certain deleterious metabolic consequences of prediabetes. This study was registered at clinicaltrials.gov as NCT01441921.

Nut consumption in relation to cardiovascular disease incidence and mortality among patients with diabetes mellitus.

Liu, G., M. Guasch-Ferre, Y. Hu, Y. Li, F.B. Hu, E.B. Rimm, J.E. Manson, K. Rexrode, Q. Sun, 2019. Nut consumption in relation to cardiovascular disease incidence and mortality among patients with diabetes mellitus. Circulation Research. doi.org/10.1161/CIRCRESAHA.118.314316

Rationale: The evidence regarding the potential health benefits of nut consumption among individuals with type 2 diabetes is limited. Objective: To examine intake of total and specific types of nuts, including tree nuts and peanuts, in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, and all-cause and cause-specific mortality among individuals with diabetes. Methods and Results: This prospective analysis included 16,217 men and women with diabetes at baseline or diagnosed during follow-up (Nurses’ Health Study: 1980-2014, Health Professionals Follow-Up Study: 1986-2014). Nut consumption was assessed using a validated food frequency questionnaire and updated every 2-4 years. During 223,682 and 254,923 person-years of follow-up, there were 3,336 incident CVD cases and 5,682 deaths. Higher total nut consumption was associated with a lower risk of CVD incidence and mortality. The multivariate-adjusted hazard ratios (95% confidence intervals) for participants who consumed 5 or more servings of total nuts per week (1 serving=28g), compared with those who consumed less than 1 serving per month, were 0.83 (0.71-0.98; P trend=0.01) for total CVD incidence, 0.80 (0.67-0.96; P trend=0.005) for CHD incidence, 0.66 (0.52-0.84; P trend<0.001) for CVD mortality, and 0.69 (0.61-0.77; P trend<0.001) for all-cause mortality. Total nut consumption was not significantly associated with risk of stroke incidence or cancer mortality. For specific types of nuts, higher tree nut consumption was associated with lower risk of total CVD, CHD incidence, and mortality due to CVD, cancer, and all causes, while peanut consumption was associated with lower all-cause mortality only (all P trend<0.001). In addition, compared with participants who did not change the consumption of total nuts from pre- to post-diabetes diagnosis, participants who increased consumption of total nuts after diabetes diagnosis had an 11% lower risk of CVD, a 15% lower CHD risk, a 25% lower CVD mortality, and a 27% lower all-cause mortality. The associations persisted in subgroup analyses stratified by sex/cohort, body mass index at diabetes diagnosis, smoking status, diabetes duration, nut consumption before diabetes diagnosis, or diet quality. Conclusions: Higher consumption of nuts, especially tree nuts, is associated with lower CVD incidence and mortality among participants with diabetes. These data provide novel evidence that supports the recommendation of incorporating nuts into healthy dietary patterns for the prevention of CVD complications and premature deaths among individuals with diabetes.

Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial.

Al Wattar, B.H., J. Dodds, A. Placzek, L. Beresford, E. Spyreli, A. Moore, A. Moore, F.J. Gonzalez Carreras, F. Austin, N. Murugesu, T.J. Roseboom, M. Bes-Rastrollo, G.A. Hitman, R. Hooper, K.S. Khan, S. Thangaratinam, for the ESTEEM study group, 2019. Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial. PLoS Med 16(7): e1002857. https://doi.org/10.1371/journal. pmed.1002857

Background: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in highrisk women. Methods and findings: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58– 1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53–0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study’s limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. Conclusions: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes.

The effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials.

Tindall, A.M., E.A. Johnston, P.M. Kris-Etherton, K.S. Petersen, 2019. The effect of nuts on markers of glycemic control: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 109:297–314.

Background: Observational evidence suggests higher nut consumption is associated with better glycemic control; however, it is unclear if this association is causal. Objectives: We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effect of tree nuts and peanuts on markers of glycemic control in adults. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted. A total of 1063 potentially eligible articles were screened in duplicate. From these articles, 40 were eligible for inclusion and data from these articles were extracted in duplicate. The weighted mean difference (WMD) between the nut intervention and control arms was determined for fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR) using the DerSimonian and Laird random-effects method. For outcomes where a limited number of studies were published, a qualitative synthesis was presented. Results: A total of 40 randomized controlled trials including 2832 unique participants, with a median duration of 3 mo (range: 1–12 mo), were included. Overall consumption of tree nuts or peanuts had a favorable effect on HOMA-IR (WMD: −0.23; 95% CI: −0.40, −0.06; I2=51.7%) and fasting insulin (WMD: −0.40μIU/mL;95% CI: −0.73, −0.07μ IU/mL; I2 = 49.4%). There was no significant effect of nut consumption on fasting blood glucose (WMD: −0.52 mg/dL;95% CI: −1.43,0.38mg/dL; I2 =53.4%) o rHbA1c (WMD: 0.02%; 95% CI: −0.01%, 0.04%; I2 =51.0%). Conclusions: Consumption of peanuts or tree nuts significantly decreased HOMA-IR and fasting insulin; there was no effect of nut consumption on HbA1c or fasting glucose. The results suggest that nut consumption may improve insulin sensitivity. In the future, well-designed clinical trials are required to elucidate the mechanisms that account for these observed effects.