Effect of tree nuts on glycemic control in diabetes: a systematic review and meta-analysis of randomized controlled dietary trials

Abstract

Background: Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.

Objective: 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.

Data sources: MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.

Study selection: 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.

Data extraction and synthesis: 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).

Results: 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.

Limitations: Majority of trials were of short duration and poor quality.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT01630980.

Conflict of interest statement

Competing Interests: CWCK has received research support from the Advanced Foods and Material Network, Agrifoods and Agriculture Canada, the Almond Board of California, the American Pistachio Growers, Barilla, the California Strawberry Commission, the Calorie Control Council, CIHR, the Canola Council of Canada, the Coca-Cola Company (investigator initiated, unrestricted grant), Hain Celestial, the International Tree Nut Council Nutrition Research and Education Foundation, Kellogg, Kraft, Loblaw Companies Ltd., Orafti, Pulse Canada, Saskatchewan Pulse Growers, Solae and Unilever. He has received travel funding, consultant fees and/or honoraria from Abbott Laboratories, the Almond Board of California, the American Peanut Council, the American Pistachio Growers, Barilla, Bayer, the Canola Council of Canada, the Coca-Cola Company, Danone, General Mills, the International Tree Nut Council Nutrition Research and Education Foundation, Kellogg, Loblaw Companies Ltd., the Nutrition Foundation of Italy, Oldways Preservation Trust, Orafti, Paramount Farms, the Peanut Institute, PepsiCo, Pulse Canada, Sabra Dipping Co., Saskatchewan Pulse Growers, Solae, Sun-Maid, Tate and Lyle, and Unilever. He is on the Dietary Guidelines Committee for the Diabetes Nutrition Study Group of the European Association for the Study of Diabetes and has served on the scientific advisory board for the Almond Board of California, the International Tree Nut Council, Oldways Preservation Trust, Paramount Farms and Pulse Canada. VH has received research support from the CIHR and the World Health Organization (WHO) for work on a systematic review and meta-analysis commissioned by WHO of the relation of saturated fatty acids with health outcomes. She received a travel award to attend a science day hosted by PepsiCo Inc. and the New York Academy of Sciences. LC has received research support from the CIHR and the Agricultural Bioproducts Innovation Program through the Pulse Research Network (PURENet), and Saskatchewan Pulse Growers. She is also a casual clinical research coordinator at Glycemic Index Laboratories. RJdS is funded by a CIHR Postdoctoral Fellowship Award and has received research support from the CIHR, the Calorie Control Council, the Canadian Foundation for Dietetic Research and the Coca-Cola Company (investigator initiated, unrestricted grant). He has served as an external resource person to WHO’s Nutrition Guidelines Advisory Group and received travel support from WHO to attend group meetings. He is the lead author of 2 systematic reviews and meta-analyses commissioned by WHO of the relation of saturated fatty acids and trans fatty acids with health outcomes. DJAJ has received research grants from Saskatchewan Pulse Growers, the Agricultural Bioproducts Innovation Program through the Pulse Research Network, the Advanced Foods and Material Network, Loblaw Companies Ltd., Unilever, Barilla, the Almond Board of California, the Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Haine Celestial, the Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, the Canola and Flax Councils of Canada, the Calorie Control Council, the CIHR, the Canada Foundation for Innovation and the Ontario Research Fund. He has been on the speaker’s panel, served on the scientific advisory board, and/or received travel support and/or honoraria from the Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd, the Griffin Hospital (for the development of the NuVal scoring system), the Coca- Cola Company, Saskatchewan Pulse Growers, Sanitarium Company, Orafti, the Almond Board of California, the American Peanut Council, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamental for Health, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter & Gamble, the Coca-Cola Company, the Griffin Hospital, Abbott Laboratories, the Canola Council of Canada, Dean Foods, the California Strawberry Commission, Haine Celestial, PepsiCo, the Alpro Foundation, Pioneer Hi- Bred International, DuPont Nutrition and Health, Spherix Consulting and WhiteWave Foods, the Advanced Foods and Material Network, the Canola and Flax Councils of Canada, the Nutritional Fundamentals for Health, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Saskatchewan Pulse Growers, the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), Nutra- Source Diagnostics, the McDougall Program, the Toronto Knowledge Translation Group (St. Michael’s Hospital), the Canadian College of Naturopathic Medicine, The Hospital for Sick Children, the Canadian Nutrition Society (CNS), the American Society of Nutrition (ASN), Arizona State University, Paolo Sorbini Foundation and the Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the United States Department of Agriculture to present the 2013 W.O. Atwater Memorial Lecture. He received the 2013 Award for Excellence in Research from the International Nut and Dried Fruit Council. He received funding and travel support from the Canadian Society of Endocrinology and Metabolism to produce mini cases for the Canadian Diabetes Association. His wife is a director and partner of Glycemic Index Laboratories, and his sister received funding through a grant from the St. Michael’s Hospital Foundation to develop a cookbook for one of his studies. JLS has received research support from the CIHR, Calorie Control Council, the Coca-Cola Company (investigator initiated, unrestricted grant), Pulse Canada, and the International Tree Nut Council Nutrition Research and Education Foundation. He has received travel funding, speaker fees, and/or honoraria from the American Heart Association, the American Society for Nutrition, the National Institute of Diabetes and Digestive and Kidney Diseases, the Canadian Diabetes Association, the Canadian Nutrition Society, the Calorie Control Council, the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, the International Life Sciences Institute North America, the International Life Sciences Institute Brazil, the University of South Carolina, the University of Alabama at Birmingham, the Canadian Sugar Institute, Oldways Preservation Trust, the Nutrition Foundation of Italy, Abbott Laboratories, Pulse Canada, Dr. Pepper Snapple Group, Corn Refiners Association, and the Coca-Cola Company. He is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of both the Canadian Diabetes Association and the European Association for the Study of Diabetes, and he is on the American Society for Nutrition writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose and high-fructose corn syrup. He is a member of the Carbohydrate Quality Consortium and an unpaid scientific advisor for the Food, Nutrition and Safety Program of the International Life Science Institute North America. His wife is an employee of Unilever Canada. No competing interests were declared by EV, SBM, AIC, AM, VHJ, LSAA, and LL. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Flow of the literature.

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.

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

Pooled effect estimate (diamond) 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.

Figure 3. Forest plot of randomized controlled trials investigating the effect of diets supplemented with tree nuts on fasting glucose in individuals with type 2 diabetes.

Pooled effect estimate (diamond) for fasting glucose (mmol/L). 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.

Figure 4. Forest plot of randomized controlled trials investigating the effect of diets supplemented with tree nuts on fasting insulin in individuals with type 2 diabetes.

Pooled effect estimate (diamond) for fasting insulin (pmol/L). Data are expressed as weighted mean differences (MD) with 95% CIs, using the generic inverse-variance random-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.

Figure 5. Forest plots of randomized controlled trials investigating the effect of diets supplemented with tree nuts on HOMA-IR in individuals with type 2 diabetes.

Pooled effect estimate (diamond) 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.

Figure 6. Publication bias funnel plots.

Publication bias funnel plots for HbA1c (A), fasting glucose (B), fasting insulin (C), and HOMA-IR (D). The solid line represents the pooled effect estimate expressed as the weighted mean difference for each analysis. The dashed lines represent pseudo-95% confidence limits. P-values displayed in the top right corner of each funnel plot are derived from quantitative assessment of publication bias by Egger’s and Begg’s tests.