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

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          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 (I 2).

          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

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          Most cited references30

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          Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp.

          Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test (OGTT). However, the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique. In this study, we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique. In this study, 153 subjects (66 men and 87 women, aged 18-71 years, BMI 20-65 kg/m2) with varying degrees of glucose tolerance (62 subjects with normal glucose tolerance, 31 subjects with impaired glucose tolerance, and 60 subjects with type 2 diabetes) were studied. After a 10-h overnight fast, all subjects underwent, in random order, a 75-g OGTT and a euglycemic insulin clamp, which was performed with the infusion of [3-3H]glucose. The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis. The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp (r = -0.02, NS). From the OGTT, we developed an index of whole-body insulin sensitivity (10,000/square root of [fasting glucose x fasting insulin] x [mean glucose x mean insulin during OGTT]), which is highly correlated (r = 0.73, P < 0.0001) with the rate of whole-body glucose disposal during the euglycemic insulin clamp. Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT. Our results demonstrate the limitations of such an approach. We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT.
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            Health Benefits of Nut Consumption

            Emilio Ros (2010)
            Nuts (tree nuts and peanuts) are nutrient dense foods with complex matrices rich in unsaturated fatty and other bioactive compounds: high-quality vegetable protein, fiber, minerals, tocopherols, phytosterols, and phenolic compounds. By virtue of their unique composition, nuts are likely to beneficially impact health outcomes. Epidemiologic studies have associated nut consumption with a reduced incidence of coronary heart disease and gallstones in both genders and diabetes in women. Limited evidence also suggests beneficial effects on hypertension, cancer, and inflammation. Interventional studies consistently show that nut intake has a cholesterol-lowering effect, even in the context of healthy diets, and there is emerging evidence of beneficial effects on oxidative stress, inflammation, and vascular reactivity. Blood pressure, visceral adiposity and the metabolic syndrome also appear to be positively influenced by nut consumption. Thus it is clear that nuts have a beneficial impact on many cardiovascular risk factors. Contrary to expectations, epidemiologic studies and clinical trials suggest that regular nut consumption is unlikely to contribute to obesity and may even help in weight loss. Safety concerns are limited to the infrequent occurrence of nut allergy in children. In conclusion, nuts are nutrient rich foods with wide-ranging cardiovascular and metabolic benefits, which can be readily incorporated into healthy diets.
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              Association of nut consumption with total and cause-specific mortality.

              Increased nut consumption has been associated with a reduced risk of major chronic diseases, including cardiovascular disease and type 2 diabetes mellitus. However, the association between nut consumption and mortality remains unclear. We examined the association between nut consumption and subsequent total and cause-specific mortality among 76,464 women in the Nurses' Health Study (1980-2010) and 42,498 men in the Health Professionals Follow-up Study (1986-2010). Participants with a history of cancer, heart disease, or stroke were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. During 3,038,853 person-years of follow-up, 16,200 women and 11,229 men died. Nut consumption was inversely associated with total mortality among both women and men, after adjustment for other known or suspected risk factors. The pooled multivariate hazard ratios for death among participants who ate nuts, as compared with those who did not, were 0.93 (95% confidence interval [CI], 0.90 to 0.96) for the consumption of nuts less than once per week, 0.89 (95% CI, 0.86 to 0.93) for once per week, 0.87 (95% CI, 0.83 to 0.90) for two to four times per week, 0.85 (95% CI, 0.79 to 0.91) for five or six times per week, and 0.80 (95% CI, 0.73 to 0.86) for seven or more times per week (P<0.001 for trend). Significant inverse associations were also observed between nut consumption and deaths due to cancer, heart disease, and respiratory disease. In two large, independent cohorts of nurses and other health professionals, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death. (Funded by the National Institutes of Health and the International Tree Nut Council Nutrition Research and Education Foundation.).
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                30 July 2014
                : 9
                : 7
                : e103376
                Affiliations
                [1 ]Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Center, St. Michael’s Hospital, Toronto, Ontario, Canada
                [2 ]Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
                [3 ]Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
                [4 ]Division of Endocrinology and Metabolism, St. Michael’s Hospital, Toronto, Ontario, Canada
                [5 ]Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada
                [6 ]College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
                [7 ]Department of Clinical Epidemiology & Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada
                [8 ]School of Medicine, Faculty of Health Sciences, Queen’s University, Kingston, Ontario, Canada
                [9 ]Department of Human Health and Nutritional Sciences, College of Biological Sciences, University of Guelph, Guelph, Ontario, Canada
                CUNY, United States of America
                Author notes

                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.

                Conceived and designed the experiments: CWCK DJAJ JLS. Analyzed the data: EV SBM AIC VH AM RJdS JLS. Wrote the paper: EV JLS. Interpretation of the data: EV SBM AIC VH AM VHJ RJdS LAL. Critical revision of the article for important intellectual content: EV CWCK SBM AIC VH AM VHJ LSAA LC LAL RJdS DJAJ JLS. Final approval of the article: EV CWCK SBM AIC VH AM VHJ LSAA LC LAL RJdS DJAJ JLS. Obtaining of funding: CWCK DJAJ JLS. Administrative, technical, or logistic support: SBM VHJ LC LSAA. Collection and assembly of data: EV SBM. Guarantors: CWCK DJAJ JLS.

                Article
                PONE-D-14-01609
                10.1371/journal.pone.0103376
                4116170
                25076495
                4b5ee3b8-135c-45a9-85b3-cb34fb49b590
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 January 2014
                : 22 June 2014
                Page count
                Pages: 13
                Funding
                This work was supported by the International Tree Nut Council Nutrition Research & Education Foundation and (Davis, California) and the Canadian Institutes of Health Research (funding reference number, 129920) through the Canada-wide Human Nutrition Trialists’ Network (NTN). The Diet, Digestive tract, and Disease (3-D) Centre, funded through the Canada Foundation for Innovation (CFI) and the Ministry of Research and Innovation’s Ontario Research Fund (ORF), provided the infrastructure for the conduct of this project. VH and AC were funded by Province of Ontario Graduate Scholarships. AC was also funded by a Canadian Institutes of Health Research (CIHR)-Fredrick Banting and Charles Best Canada Graduate Scholarship and Banting and Best Diabetes Centre (BBDC)-Novo Nordisk Studentship. RJdS was funded by a CIHR Postdoctoral Fellowship Award. DJAJ was funded by the Government of Canada through the Canada Research Chair Endowment. None of the sponsors had a role in any aspect of the present study, including design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, approval of the manuscript or decision to publish.
                Categories
                Research Article
                Biology and Life Sciences
                Nutrition
                Medicine and Health Sciences
                Endocrinology
                Diabetic Endocrinology
                Medical Humanities
                Evidence-Based Medicine
                Metabolic Disorders
                Diabetes Mellitus
                Type 2 Diabetes

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