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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.

Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial.

Jenkins, D.J.A., C.W.C. Kendall, B. Lamarche, M.S. Banach, K. Srichaikul, E. Vidgen, S. Mitchell, T. Parker, S. Nishi, B. Bashyam, R.J. de Souza, C. Ireland, S.C. Pichika, J. Beyene, J.L. Sievenpiper, R.G. Josse, 2018. Nuts as a replacement for carbohydrates in the diabetic diet: a reanalysis of a randomised controlled trial. Diabetologia. 61: 1734. https://doi.org/10.1007/s00125-018-4628-9

Aims/hypothesis: In line with current advice, we assessed the effect of replacing carbohydrate consumption with mixed nut consumption, as a source of unsaturated fat, on cardiovascular risk factors and HbA1c in type 2 diabetes. The data presented here are from a paper that was retracted at the authors’ request ( https://doi.org/10.2337/dc16-rt02) owing to lack of adjustment for repeated measures in the same individual. Our aim, therefore, was to fix the error and add new complementary data of interest, including information on clotting factors and LDL particle size. Methods: A total of 117 men and postmenopausal women with type 2 diabetes who were taking oral glucose-lowering agents and with HbA1c between 47.5 and 63.9 mmol/mol (6.5–8.0%) were randomised after stratification by sex and baseline HbA1c in a parallel design to one of three diets for 3 months: (1) ‘full-dose nut diet’ (n = 40): a diet with 2.0 MJ (477 kcal) per 8.4 MJ (2000 kcal) energy provided as mixed nuts (75 g/day); (2) ‘full-dose muffin diet’ (n = 39): a diet with 1.97 MJ (471 kcal) per 8.4 MJ (2000 kcal) energy provided as three whole-wheat muffins (188 g/day), with a similar protein content to the nuts, and the same carbohydrate-derived energy content as the monounsaturated fatty acid-derived energy content in the nuts; or (3) ‘half-dose nut diet’ (n = 38): a diet with 1.98 MJ (474 kcal) per 8.4 MJ (2000 kcal) energy provided as half portions of both the nuts and muffins. The primary outcome was change in HbA1c. The study was carried out in a hospital clinical research centre and concluded in 2008. Only the statistician, study physicians and analytical technicians could be blinded to the group assessment. Results: A total of 108 participants had post-intervention data available for analysis (full-dose nut group, n = 40; full-dose muffin group, n = 35; half-dose nut group, n = 33). Compared with the full-dose muffin diet, the full-dose nut diet provided 9.2% (95% CI 7.1, 11.3) greater total energy intake from monounsaturated fat. The full-dose nut diet (median intake, 75 g/day) also reduced HbA1c compared with the full-dose muffin diet by −2.0 mmol/mol (95% CI −3.8, −0.3 mmol/mol) (−0.19% [95% CI −0.35%, −0.02%]), (p = 0.026). Estimated cholesterol levels in LDL particles with a diameter <255 ångström [LDL-c<255Å]) and apolipoprotein B were also significantly decreased after the full-dose nut diet compared with the full-dose muffin diet. According to the dose response, the full-dose nut diet is predicted to reduce HbA1c (−2.0 mmol/mol [−0.18%]; p = 0.044), cholesterol (−0.25 mmol/l; p = 0.022), LDL-cholesterol (−0.23 mmol/l; p = 0.019), non-HDL-cholesterol (−0.26 mmol/l; p = 0.020), apolipoprotein B (−0.06 g/l, p = 0.013) and LDL-c<255Å (−0.42 mmol/l; p < 0.001). No serious study-related adverse events occurred, but one participant on the half-dose nut diet was hospitalised for atrial fibrillation after shovelling snow. Conclusions/interpretation: Nut intake as a replacement for carbohydrate consumption improves glycaemic control and lipid risk factors in individuals with type 2 diabetes.

The antioxidant activity of pistachios reduces cardiac tissue injury of acute ischemia/reperfusion (I/R) in diabetic Streptozotocin (STZ)-induced hyperglycaemic rats.

Di Paola, R., R. Fusco, E. Gugliandolo, R. D’Amico, M. Campolo, S. Latteri, A. Carughi, G. Mandalari, S. Cuzzocrea, 2018. The antioxidant activity of pistachios reduces cardiac tissue injury of acute ischemia/reperfusion (I/R) in diabetic Streptozotocin (STZ)-induced hyperglycaemic rats. Front Pharmacol. 9:51. doi: 10.3389/fphar.2018.00051. eCollection 2018.

Diabetes mellitus is an important risk factor for the development of heart pathology. Myocardial infarction is the cause of death occurring after prolonged ischemia of the coronary arteries. Restoration of blood flow is the first intervention against heart attack, although the process of restoring blood flow to the ischemic myocardium could cause additional injury. This phenomenon, termed myocardial ischemia-reperfusion (MI-R) injury, is characterized by the formation of oxygen radicals. Pistachios have significant glucose- and insulin-lowering effects and can improve the inflammatory contest by downregulating both the expression and the circulating levels of several metabolic risk markers. The monocyte/macrophage cell line J774 was used to assess the extent of protection by natural raw (NP) and roasted salted (RP) pistachios against lipopolysaccharide (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR) injection in the paw. This study evaluates the antioxidant properties of pistachios on the inflammatory process associated with myocardial ischemia/reperfusion injury (I/R) in diabetic rats. Rats were pre-treated with either NP or RP pistachios (30 mg/kg) 18 h prior to the experimental procedure. Results: Here, we demonstrated that treatment with NP reduced myocardial tissue injury, neutrophil infiltration, adhesion molecules (ICAM-1, P-selectin) expression, proinflammatory cytokines (TNF-α, IL-1β) production, nitrotyrosine and PAR formation, NF-κB expression and apoptosis (Bax, Bcl-2) activation. This data clearly shows modulation of the inflammatory process, associated with MI-R injury, following administration of pistachios.