Effects of a Mediterranean eating plan on the need for glucose-lowering medications in participants with type 2 diabetes: a subgroup analysis of the PREDIMED trial.

OBJECTIVE: To examine the effects of two Mediterranean eating plans (Med-EatPlans) versus a low-fat eating plan on the need for glucose-lowering medications. RESEARCH DESIGN AND METHODS: From the PREDIMED trial, we selected 3,230 participants with type 2 diabetes at baseline. These participants were randomly assigned to one of three eating plans: Med-EatPlan supplemented with extra virgin olive oil (EVOO), Med-EatPlan supplemented with mixed nuts, or a low-fat eating plan (control). In a subgroup (15%), the allocation was done in small clusters instead of using individual randomization, and the clustering effect was taken into account in the statistical analysis. In multivariable time-to-event survival models, we assessed two outcomes: 1) introduction of the first glucose-lowering medication (oral or injectable) among participants on lifestyle management at enrollment and 2) insulin initiation. RESULTS: After a median follow-up of 3.2 years, in multivariable analyses adjusting for baseline characteristics and propensity scores, the hazard ratios (HRs) of starting a first glucose-lowering medication were 0.78 (95% CI 0.62-0.98) for Med-EatPlan + EVOO and 0.89 (0.71-1.12) for Med-EatPlan + nuts, compared with the control eating plan. After a median follow-up of 5.1 years, the adjusted HRs of starting insulin treatment were 0.87 (0.68-1.11) for Med-EatPlan + EVOO and 0.89 (0.69-1.14) for Med-EatPlan + nuts compared with the control eating plan. CONCLUSIONS: Among participants with type 2 diabetes, a Med-EatPlan + EVOO may delay the introduction of new-onset glucose-lowering medications. The Med-EatPlan did not result in a significantly lower need for insulin.

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Effects of nut and seed consumption on markers of glucose metabolism in adults with prediabetes: a systematic review of randomized controlled trials.

The primary aim was to investigate the effects of nut and seed consumption on markers of glucose metabolism in adults with prediabetes. Studies with a randomized controlled trial (RCT) design, comparing the effects of a diet containing nuts or seeds against a diet without nuts or seeds in adults with prediabetes, were considered eligible. Primary outcome measures included fasting plasma glucose (FPG), 2-hour plasma glucose (PG) during oral glucose tolerance test (OGTT) and glycated haemoglobin (HbA1c) concentrations. Studies were identified by searching PubMed and Scopus electronic databases and by checking full texts and reference lists of relevant records. Risk of bias was assessed using the Cochrane Collaboration's tool. We included 5 RCTs involving 371 adults with prediabetes or at risk of diabetes; 3 RCTs investigated the effects of whole nut consumption and 2 the effects of ground flaxseed consumption. Consumption of 57 g/day pistachios or mean intake of 60 g/day almonds for 4 months improved FPG and fasting plasma insulin (FPI) concentrations, insulin resistance, cellular glucose uptake in lymphocytes and β-cell function. Consumption of 56 g/day walnuts for 6 months was not found to affect FPG or HbA1c concentrations. Consumption of 13 g/day flaxseed for 3 months improved FPG and FPI concentrations and insulin resistance. In a second study, however, flaxseed consumption was not found to affect markers of glucose metabolism. The risk of bias was generally low, thus the reported results could be reliable. Further investigation of nut and seed consumption effects in the field of prediabetes is warranted.

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Mechanisms Underlying the Cardiometabolic Protective Effect of Walnut Consumption in Obese Subjects: A Cross‐Over, Randomized, Double‐Blinded, Controlled Inpatient Physiology Study.

AIMS: To assess the effects of walnuts on cardiometabolic outcomes in obese subjects and to explore underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic, and microbiome analysis integrated with lipid particle fractionation, appetite-regulating hormones and hemodynamic measurements. MATERIALS AND METHODS: 10 obese subjects were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. Patients participated in two 5-day inpatient stays during which they consumed a smoothie containing 48g walnuts or a macronutrient-matched placebo smoothie without nuts, with a one-month washout period between the two visits. RESULTS: Walnut consumption improved aspects of the lipid profile, i.e. reduced fasting small and dense LDL particles (p<.02) and increased postprandial large HDL particles (p<.01). Lipoprotein Insulin Resistance Score, glucose and insulin AUC decreased significantly after walnut consumption (p<.01, p<.02, p<.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with 8 of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. Peptide YY AUC significantly increased after walnut consumption (p<.03). No major significant changes in hemodynamic, metabolomic analysis or in host health-promoting bacteria such as Faecalibacterium were found. CONCLUSIONS: These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic parameters. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption that may explain the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality. This article is protected by copyright. All rights reserved.

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Effects of Daily Consumption of Cashews on Oxidative Stress and Atherogenic Indices in Patients with Type 2 Diabetes: A Randomized, Controlled-Feeding Trial.

BACKGROUND: Cashews, as the main source of monounsaturated (MUFAs) and polyunsaturated (PUFAs) fatty acids, are associated with reduced risk of cardiovascular diseases. Despite evidence for beneficial effects of nuts on lipid profile and glycemic control, to the authors' best knowledge, little is known about cashews. METHODS: An eight-week, randomized, isocaloric, controlled-feeding study was conducted on 50 patients with type 2 diabetes mellitus (T2DM) randomly assigned to either the control or intervention group (10% of total calorie from cashews). Weight, fasting plasma glucose (FPG), serum insulin concentration and sensitivity, lipid profile ratio, high-sensitive C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and paraoxonase-1 (PON-1) were measured at baseline and after eight weeks of intervention adjusted for age, gender, baseline values of FPG, insulin, HOMA-IR (homeostatic model assessment of insulin resistance), fiber, and both baseline and post-intervention vitamin C levels as covariates. RESULTS: Weight, body mass index (BMI), and waist circumference (WC) were not significantly different in the groups after eight weeks of intervention, as well as between the two groups, compared with the baseline measures. At the end of the study, serum insulin and low-density lipoprotein-cholesterol-to-high-density lipoprotein-cholesterol (LDL-C/HDL-C) ratio significantly decreased in the cashews group compared with those of the controls (P = 0.01 and P = 0.04, respectively). Although, HOMA-IR decreased significantly in the cashews group (P = 0.03), changes were not significant compared with the baseline measures (P = 0.056). Despite more increase in PON-1 activity in the cashews group, the changes were not statistically significant. CONCLUSIONS: Daily consumption of cashews reduced serum insulin and LDL-C/HDL-C ratio in patients with T2DM. However, further studies with larger sample sizes and more duration are needed to confirm the current study results.

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Nuts and Cardio-Metabolic Disease: A Review of Meta-Analyses.

OBJECTIVES: Accumulating epidemiological and intervention evidence suggest that nut consumption is associated with reduced incidence of some cardiometabolic diseases. However, to date no review of meta-analyses of epidemiological and intervention studies has evaluated the effects of nut consumption on cardiometabolic disease. Design/Results: Electronic searches for meta-analyses of epidemiological and intervention studies were undertaken in PubMed®/MEDLINE®. Meta-analyses of prospective studies show that nut consumption appears to be associated with reduced all-cause mortality by 19⁻20% (n = 6), cardiovascular disease (CVD) incidence (19%; n = 3) and mortality (25%; n = 3), coronary heart disease (CHD) incidence (20⁻34%; n = 2) and mortality (27⁻30%; n = 2) and stroke incidence (10⁻11%; n = 7) and mortality (18%; n = 2). No association between nut consumption and the risk of type 2 diabetes mellitus (T2DM) was observed in meta-analyses of prospective studies, whereas a decrease in fasting blood glucose ranging from 0.08 to 0.15 mmol/L was observed in 3 meta-analyses of intervention studies. In the interventions, nut consumption also had favorable effects on total cholesterol (0.021 to 0.28 mmol/L reduction from 8 meta-analyses of interventions) and low-density lipoprotein cholesterol (0.017 to 0.26 mmol/L reduction from 8 meta-analyses of interventions) and endothelial function (0.79 to 1.03% increase in flow-mediated dilation from 4 meta-analyses of interventions). Nut consumption did not significantly affect body weight. Nut consumption had no effect on inflammatory markers in intervention studies. The effect on blood pressure was inconsistent. A higher nut consumption was associated with a lower incidence of hypertension in prospective studies, while nut consumption did not improve blood pressure in intervention studies. CONCLUSIONS: Nut consumption appeared to be associated with lower all-cause mortality and CVD and CHD mortality. There was no association between nut consumption and the incidence of T2DM although fasting blood glucose is decreased in intervention studies. In intervention studies nuts lower total cholesterol and low-density lipoprotein cholesterol (LDL-C).

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A Mediterranean Diet with an Enhanced Consumption of Extra Virgin Olive Oil and Pistachios Improves Pregnancy Outcomes in Women Without Gestational Diabetes Mellitus: A Sub-Analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study.

AIMS: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy. METHODS: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age. RESULTS: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced. CONCLUSION: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women.

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Effect of dried fruit on postprandial glycemia: A randomized acute-feeding trial.

Background/Objectives: To investigate the effect of dried fruit in modifying postprandial glycemia, we assessed the ability of 4 dried fruits (dates, apricots, raisins, sultanas) to decrease postprandial glycemia through three mechanisms: a glycemic index (GI) effect, displacement effect, or ‘catalytic’ fructose effect. Subjects/Methods: We conducted an acute randomized, multiple-crossover trial in an outpatient setting in 10 healthy adults. Participants received 3 white bread control meals and 12 dried fruit test meals in random order. The test meals included each of 4 dried fruits (dates, apricots, raisins, sultanas) alone (GI effect), 4 of the dried fruits displacing half the available carbohydrate in white bread (displacement effect), or 4 of the dried fruits providing a small ‘catalytic’ dose (7.5 g) of fructose added to white bread (‘catalytic’ fructose effect). The protocol followed the ISO method for the determination of GI (ISO 26642:2010). The primary outcome was mean ± SEM GI (glucose scale) for ease of comparison across the three mechanisms. Results: Ten healthy participants (7 men, 3 women; mean ± SD age and BMI: 39 ± 12 years and 25 ± 2 kg/m2) were recruited and completed the trial. All dried fruit had a GI below that of white bread (GI = 71); however, only dried apricots (GI = 42 ± 5), raisins (GI = 55 ± 5), and sultanas (51 ± 4) showed a significant GI effect (P < 0.05). When displacing half the available carbohydrate in white bread, all dried fruit lowered the GI; however, only dried apricots (GI = 57 ± 5) showed a significant displacement effect (P = 0.025). None of the dried fruits showed a beneficial ‘catalytic’ fructose effect. Conclusions: In conclusion, dried fruits have a lower GI and reduce the glycemic response of white bread through displacement of half of the available carbohydrate. Longer-term randomized trials are needed to confirm whether dried fruit can contribute to sustainable improvements in glycemic control.

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Medical nutrition therapy for gestational diabetes mellitus based on Mediterranean Diet principles: a subanalysis of the St Carlos GDM Prevention Study.

OBJECTIVES: To assess whether Mediterranean Diet (MedDiet)-based medical nutrition therapy facilitates near-normoglycemia in women with gestational diabetes mellitus (GDMw) and observe the effects on adverse pregnancy outcomes. RESEARCH DESIGN AND METHODS: This is a secondary analysis of the St Carlos GDM Prevention Study, conducted between January and December 2015 in Hospital Clínico San Carlos (Madrid, Spain). One thousand consecutive women with normoglycemia were included before 12 gestational weeks (GWs), with 874 included in the final analysis. Of these, 177 women were diagnosed with gestational diabetes mellitus (GDM) and 697 had normal glucose tolerance. All GDMw received MedDiet-based medical nutrition therapy with a recommended daily extra virgin olive oil intake ≥40 mL and a daily handful of nuts. The primary goal was comparison of hemoglobin A1c (HbA1c) levels at 36-38 GWs in GDMw and women with normal glucose tolerance (NGTw). RESULTS: GDMw as compared with NGTw had higher HbA1c levels at 24-28 GWs (5.1%±0.3% (32±0.9 mmol/mol) vs 4.9%±0.3% (30±0.9 mmol/mol), p=0.001). At 36-38 GWs values were similar between the groups. Similarly, fasting serum insulin and homeostatic model assessment insulin resitance (HOMA-IR) were higher in GDMw at 24-28 GWs (p=0.001) but became similar at 36-38 GWs. 26.6% of GDMw required insulin for glycemic control. GDMw compared with NGTw had higher rates of insufficient weight gain (39.5% vs 22.0%, p=0.001), small for gestational age (6.8% vs 2.6%, p=0.009), and neonatal intensive care unit admission (5.6% vs 1.7%, p=0.006). The rates of macrosomia, large for gestational age, pregnancy-induced hypertensive disorders, prematurity and cesarean sections were comparable with NGTw. CONCLUSIONS: Using a MedDiet-based medical nutrition therapy as part of GDM management is associated with achievement of near-normoglycemia, subsequently making most pregnancy outcomes similar to those of NGTw.

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A Randomized Controlled Trial to Compare the Effect of Peanuts and Almonds on the Cardio-Metabolic and Inflammatory Parameters in Patients with Type 2 Diabetes Mellitus.

A low carbohydrate diet (LCD), with some staple food being replaced with nuts, has been shown to reduce weight, improve blood glucose, and regulate blood lipid in patients with type 2 diabetes mellitus (T2DM). These nuts include tree nuts and ground nuts. Tree nut consumption is associated with improved cardio-vascular and inflammatory parameters. However, the consumption of tree nuts is difficult to promote in patients with diabetes because of their high cost. As the main ground nut, peanuts contain a large number of beneficial nutrients, are widely planted, and are affordable for most patients. However, whether peanuts and tree nuts in combination with LCD have similar benefits in patients with T2DM remains unknown; although almonds are the most consumed and studied tree nut. This study sought to compare the effect of peanuts and almonds, incorporated into a LCD, on cardio-metabolic and inflammatory measures in patients with T2DM. Of the 32 T2DM patients that were recruited, 17 were randomly allocated to the Peanut group (n = 17) and 15 to the Almond group (n = 15) in a parallel design. The patients consumed a LCD with part of the starchy staple food being replaced with peanuts (Peanut group) or almonds (Almond group). The follow-up duration was three months. The indicators for glycemic control, other cardio-metabolic, and inflammatory parameters were collected and compared between the two groups. Twenty-five patients completed the study. There were no significant differences in the self-reported dietary compliance between the two groups. Compared with the baseline, the fasting blood glucose (FBG) and postprandial 2-h blood glucose (PPG) decreased in both the Peanut and Almond groups (p < 0.05). After the intervention, no statistically significant differences were found between the Peanut group and the Almond group with respect to the FBG and PPG levels. A decrease in the glycated hemoglobin A1c (HbA1c) level from the baseline in the Almond group was found (p < 0.05). However, no significant difference was found between the two groups with respect to the HbA1c level at the third month. The peanut and almond consumption did not increase the body mass index (BMI) and had no effect on the blood lipid profile or interleukin-6 (IL-6).In conclusion, incorporated into a LCD, almonds and peanuts have a similar effect on improving fasting and postprandial blood glucose among patients with T2DM. However, more studies are required to fully establish the effect of almond on the improvement of HbA1c.

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The impact of nuts consumption on glucose/insulin homeostasis and inflammation markers mediated by adiposity factors among American adults.

BACKGROUND: Inconclusive results have been published regarding the impact of nut consumption on glucose/insulin homeostasis and inflammatory factors. Furthermore, it remains unanswered whether adiposity factors could mediate the association between nut consumption, glucose/insulin homeostasis and inflammatory markers; this is what the current study aims to investigate. RESULTS: From a total of 16,784 individuals, 48.2% participants were men; overall mean age was 47.2 years. Age-, sex-, energy intake and race-adjusted mean of serum C-reactive protein (CRP)(0.49 to 0.26 mg/dl), apolipoprotein-β (apo- β) (95.6 to 90.8 mg/dl), glucose/insulin homeostasis parameters and triglyceride-glucose index (TyG) index (8.32 to 7.95) significantly decreased as the quartile of nut intake increased (all p < 0.001). We found that all evaluated potential mediators had significant and positive associations with markers of glucose/insulin homeostasis or inflammation (all p < 0.001). With regard to BMI, the mediated effects were significant for the associations between nut consumption and CRP, fasting blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride to high-density lipoprotein (TG:HDL) ratio and TyG index (all p < 0.001). As for WC, it had mediator impact on CRP, fasting blood glucose, HbA1c, TG:HDL ratio and TyG index (all p < 0.001). apVAT played no mediation role for any association (all p > 0.05). CONCLUSIONS: This is the first study which quantify the role of nut consumption on inflammatory and glucose/insulin homeostasis markers. Nut intake was inversely associated with inflammatory and glucose/insulin homeostasis markers. Certain adiposity indexes (i.e. BMI and WC) mediated these associations. These findings convey an important message for the crucial role of weight management with dietary recommendations. METHOD: We extracted data from the National Health and Nutrition Examination Survey (2005-2010) on nut consumption to evaluate the association between nut intake and markers of glucose/insulin homeostasis and inflammation. We assessed whether this link, if any, is mediated or affected by adiposity factors, including body mass index (BMI), waist circumference (WC, marker of central adiposity), anthropometrically predicted visceral adipose tissue (apVAT), visceral adiposity index (VAI, indicator of adipose distribution) and lipid accumulation product (LPA, novel index of central lipid accumulation). Analysis of co-variance and conceptus causal mediation analysis were conducted based on survey design and sample weights.
 

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