Forest plots of controlled clinical trials investigating the effect of ginseng on glycated hemoglobin.

<p>The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trial <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Elbourne1" target="_blank">[18]</a>. Data are mean differences (MD) with 95% CI. <i>P</i> values are for Generic Inverse Variance random effects models. Inter-study heterogeneity was tested by the Cochran Q statistic at a significance level of <i>P</i> <0.10 and quantified by the I² statistic, where I² ≥ 50% is considered to be evidence of substantial heterogeneity.</p

Flow of the literature search for the effect of ginseng on glycemic outcomes (FBG, FPI, HbA1c, and HOMA-IR).

<p>Flow of the literature search for the effect of ginseng on glycemic outcomes (FBG, FPI, HbA1c, and HOMA-IR).</p

Forest plots of controlled clinical trials investigating the effect of ginseng on homeostasis model assessment of insulin resistance.

<p>The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trials <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Elbourne1" target="_blank">[18]</a>. Data are mean differences (MD) with 95% CI. <i>P</i> values are for Generic Inverse Variance random effects models. Inter-study heterogeneity was tested by the Cochran Q statistic at a significance level of <i>P</i> <0.10 and quantified by the I² statistic, where I² ≥ 50% is considered to be evidence of substantial heterogeneity.</p

Characteristics of Studies Investigating the Effect of Ginseng on Glycemic Outcomes.

<p>Abbreviations: T1DM – Type 1 Diabetes mellitus; T2DM – Type 2 Diabetes mellitus; Pre-DM – Pre-diabetes Mellitus; EHPT – Essential hypertension; F – Female; M – Male; BMI – Body mass index; C – Control group; T – Treatment group; T1 – Treatment group #1; T2 – Treatment group #2; T3 – Treatment group #3; IP – Inpatient; OP – Outpatient; MQS – Heyland Methodological Quality Score; N/R – Not reported.</p><p>*Studies by Sotaniemi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Sotaniemi1" target="_blank">[7]</a>, Yoon et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Yoon1" target="_blank">[30]</a>, and Reeds et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Reeds1" target="_blank">[25]</a> contained multiple comparisons, and to mitigate unit-of-analysis error, we combined groups to create a single pairwise comparison.</p>†<p>Pre-DM included subjects with either Impaired Fasting Glucose or Impared Glucose Tolerance.</p>‡<p>Pre-study baseline BMI is listed. The study by Rhee et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Rhee1" target="_blank">[26]</a> did not report SD for the mean BMI of participants.</p>§<p>Pre-study baseline endpoints are listed. In studies were these values were not reported, the start value of control was assumed to be equivalent to baseline and was reported. Where start of control value was not given, of control value was assumed to be equivalent to baseline and was reported. Assumed values are reported in bold. The study by Reay et al. (a) & (b) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Reay1" target="_blank">[24]</a> used n = 23 and n = 14 respectively for reporting data on fasting blood glucose, n = 17 and n = 12 respectively for reporting data on fasting plasma insulin, and n = 18 and n = 11 respectively for reporting data on HbA1c.</p><p>∥Ginseng dose is reported individually for trials with multiple treatment groups.</p>¶<p>All ginseng doses were compared to placebo, a control group that did not receive ginseng, or fermented soybean.</p><p>**Study quality was assessed by the Heyland Methodological Quality Score (MQS) and trials with a score ≥ 8 were considered to be of high quality.</p>††<p>Agency funding is that from government, university or not-for-profit health agency sources. None of the trialists declared conflicts of interest.</p><p>All data is expressed as mean ± SD.</p><p>Characteristics of Studies Investigating the Effect of Ginseng on Glycemic Outcomes.</p

Forest plots of controlled clinical trials investigating the effect of ginseng on FBG.

<p>The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trials <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0107391#pone.0107391-Elbourne1" target="_blank">[18]</a>. Data are mean differences (MD) with 95% CI. <i>P</i> values are for Generic Inverse Variance random effects models. Inter-study heterogeneity was tested by the Cochran Q statistic at a significance level of <i>P</i> <0.10 and quantified by the I² statistic, where I² ≥ 50% is considered to be evidence of substantial heterogeneity.</p

Forest plots of randomized controlled trials investigating the effect of diets supplemented with tree nuts on HOMA-IR in individuals with type 2 diabetes.

<p>Pooled effect estimate (<i>diamond</i>) for homeostasis model assessment of insulin resistance (HOMA-IR). Data are expressed as weighted mean differences (MD) with 95% CIs, using the generic inverse-variance fixed-effects model. Paired analyses were applied to all crossover trials. Inter-study heterogeneity was tested by the Cochran Q-statistic and quantified by I² at a significance level of P<0.10. n = number of participants in each treatment group.</p

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

<div><p>Background</p><p>Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.</p><p>Objective</p><p>To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.</p><p>Data Sources</p><p>MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.</p><p>Study Selection</p><p>Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.</p><p>Data Extraction and Synthesis</p><p>Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²).</p><p>Results</p><p>Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.</p><p>Limitations</p><p>Majority of trials were of short duration and poor quality.</p><p>Conclusions</p><p>Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01630980?term=NCT01630980&rank=1" target="_blank">NCT01630980 </a></p></div

Trial Characteristics,

<p>BMI = body mass index; C = crossover; CHO = carbohydrate; E = energy; HF = high fat; HOMA-IR = homeostasis model assessment of insulin resistance; IP = inpatient; LF = low fat; M = men; Met = metabolic feeding control; MQS = Heyland Methodological Quality Score; N/A = not available; NCEP = National Cholesterol Education Program; O = obese and overweight; OP = outpatient; P = parallel; SD = standard deviation; Supp = supplement feeding control; T2D = type 2 diabetes; W = women; wk = week; y = years.</p><p>*The number of participants listed for each trial in this column is the number of participants that completed the trial and therefore the number used in our analyses. The baseline characteristics reported by these trials were based on the number of participants listed here with the exception of 3 trials, Tapsell et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Tapsell1" target="_blank">[36]</a>, Ma et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Ma1" target="_blank">[35]</a>, and Darvish Damavandi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-DamavandiRD1" target="_blank">[38]</a> where the values for mean age and/or mean body weight or BMI were derived from the number of participants present at baseline, a number that was different from the number of participants that completed the trial due to a per-protocol with drop-outs analysis. The number of participants present at baseline for these trials are as follows: Tapsell et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Tapsell1" target="_blank">[36]</a>, n = 50; Ma et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Ma1" target="_blank">[35]</a>, n = 24; Darvish Damavandi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-DamavandiRD1" target="_blank">[38]</a>, n = 50; Sauder et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Sauder1" target="_blank">[29]</a>, n = 30.</p>†<p>Baseline body weight or weight (kg) while receiving the control treatment in cross over trials, and baseline body weight in each treatment group in parallel trials. Baseline BMI values (kg/m²) are only reported when no data on weight were available.</p>‡<p>Countries are abbreviated using three letter country codes (ISO 3166-1 alpha-3 codes).</p>§<p>Metabolic feeding control (Met) was the provision of all meals, snacks, and study supplements (tree nuts) consumed during the study under controlled conditions. Supplement feeding control (Supp) was the provision of study supplements only.</p><p>|| Doses and % E (energy) preceded by “∼” represent values calculated on the basis of average reported energy intake of participants and average reported energy values of tree nuts from the USDA National Nutrient Database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-US3" target="_blank">[59]</a>.</p>¶<p>All nut types were provided in whole form with the exception of 2 trials: Lovejoy et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Lovejoy1" target="_blank">[27]</a> and Li et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Li1" target="_blank">[34]</a>, which incorporated tree nuts into various entrées and snack foods (i.e. muffins, trail mixes, deserts, etc.).</p><p>**Comparators refers to 1) reference food(s) energy matched in exchange for tree nuts or 2) isocaloric control diet similar to the intervention diet but without tree nuts.</p>††<p>Planned energy from Carbohydrate:Protein:Fat. Measured energy end values from carbohydrate, protein, and fat are reported only if the study did not state the planned energy of prescribed diets.</p>‡‡<p>Trials with a MQS score ≥8 were considered to be of higher quality.</p>§§<p>Agency funding is that from government, university, or not-for-profit health agency sources. None of the trialists declared any conflicts of interest with the exception of Jenkins et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-Jenkins1" target="_blank">[33]</a> and Darvish Damavandi et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103376#pone.0103376-DarvishDamavandiR1" target="_blank">[32]</a>.</p><p>|||| In this study participants randomized into the almond group were instructed to consume this dose 5 days/week.</p>¶¶<p>Mixed nuts included almonds, cashews, hazelnuts, macadamia nuts, peanuts, pecans, pistachios, walnuts.</p><p>***43% of the participants were obese and wished to lose weight; although this was not a weight loss study, they were given advice on portion size and fat intake to help them meet their weight-reduction objective.</p>†††<p>Data for this study was limited since the study’s conferences abstract and correspondence with the authors were the only sources of available data.</p

Flow of the literature.

<p>Summary of search and selection process consists of the number of studies initially identified through database and manual search, excluded based on title and abstract, reviewed in full, excluded after full review, and final number of trials included in the meta-analysis.</p

Forest plot of randomized controlled trials investigating the effect of diets supplemented with tree nuts on HbA1c in individuals with type 2 diabetes.

<p>Pooled effect estimate (<i>diamond</i>) for HbA1c (%). Data are expressed as weighted mean differences (MD) with 95% CIs, using the generic inverse-variance fixed effects model. Paired analyses were applied to all crossover trials. Inter-study heterogeneity was tested by the Cochran Q-statistic and quantified by I² at a significance level of P<0.10. n = number of participants in each treatment group.</p