Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies

Abstract

Background: Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies.

Methods: We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results: Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories.

Interpretation: Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates.

Trial registration: ClinicalTrials.gov, no. NCT01608620.

Conflict of interest statement

Competing interests: Russell de Souza has served as an external resource person to the World Health Organization (WHO) Nutrition Guidance Expert Advisory Group (NUGAG) Subgroup on Diet and Health (guidelines for trans fats and saturated fats), and received renumeration from WHO for travel and accommodation. He also received compensation for contract research conducted for the Institute of Nutrition, Metabolism, and Diabetes at the Canadian Institutes of Health Research (CIHR), Health Canada and WHO. He has received research grants from the Canadian Foundation for Dietetic Research and CIHR, and lecture fees from McMaster Children’s Hospital. Vanessa Ha has received research support from WHO. She has received a travel award and doctoral scholarship from CIHR. Alexandra Jenkins is part owner, Vice-President and Director of Research for Glycemic Index Laboratories, Toronto, Ont. She has received research support from the Canadian Diabetes Association (CDA). Thomas Wolever is part owner and President of Glycemic Index Laboratories. Cyril Kendall has received research support from the Advanced Foods and Materials Network, Agricultural Bioproducts Innovation Program through the Pulse Research Network, Agriculture and Agri-Food Canada, Almond Board of California, Barilla, Calorie Control Council, CIHR, Canola Council of Canada, The Coca-Cola Company, The International Tree Nut Council Nutrition Research & Education Foundation, Kellogg, Loblaw Companies Ltd., Pulse Canada, Saskatchewan Pulse Growers and Unilever. He has received consultant fees from American Pistachio Growers; speaker fees from American Peanut Council, Tate & Lyle and The WhiteWave Foods Company; and travel funding from Sabra Dipping Company, Tate & Lyle, International Tree Nut Council Research & Education Foundation, California Walnut Commission, Sun-Maid, The Peanut Institute, General Mills, Oldways Foundation and International Nut and Dried Fruit Council Foundation. He is a member of the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the European Association for the Study of Diabetes (EASD), the Diabetes and Nutrition Study Group of the EASD and the International Carbohydrate Quality Consortium, and is the Director for the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. David Jenkins has received research grants from Saskatchewan Pulse Growers, Agricultural Bioproducts Innovation Program through the Pulse Research Network, Advanced Foods and Materials Network, Loblaw Companies Ltd., Unilever, Barilla, Almond Board of California, Agriculture and Agri-Food Canada, Pulse Canada, Kellogg’s Canada, Quaker Oats Canada, Proctor & Gamble Technical Centres, Bayer Consumer Care (Springfield, New Jersey), PepsiCo/Quaker, International Nut and Dried Fruit Council Foundation, Soyfoods Association of North America, The Coca-Cola Company (investigator initiated, unrestricted grant), Solae, Hain Celestial, Sanitarium Company, Orafti, International Tree Nut Council Nutrition Research & Education Foundation, The Peanut Institute, Canola Council of Canada, Flax Council of Canada, Calorie Control Council, CIHR, Canada Foundation for Innovation (CFI) and 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 Almond Board of California, Canadian Agriculture Policy Institute, Loblaw Companies Ltd., Griffin Hospital (for the development of the NuVal scoring system), The Coca-Cola Company, EPICURE, Danone, Diet Quality Photo Navigation, Saskatchewan Pulse Growers, Sanitarium Company, Orafti, American Peanut Council, The International Tree Nut Council Nutrition Research & Education Foundation, The Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health, Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg’s, Quaker Oats, Procter & Gamble, Abbott Laboratories, Canola Council of Canada, Dean Foods, California Strawberry Commission, Hain Celestial, PepsiCo, Alpro Foundation, Pioneer Hi-Bred International, DuPont Nutrition and Health, Spherix Consulting, The WhiteWave Foods Company, Advanced Foods and Materials Network, Flax Council of Canada, Nutritional Fundamentals for Health, Agriculture and Agri-Food Canada, Canadian Agri-Food Policy Institute, Pulse Canada, Soyfoods Association of North America, Nutrition Foundation of Italy (NFI), Nutrasource Diagnostics, McDougall Program, Toronto Knowledge Translation Working Group (St. Michael’s Hospital), Canadian College of Naturopathic Medicine, The Hospital for Sick Children, Canadian Nutrition Society (CNS), American Society for Nutrition (ASN), Arizona State University, Paolo Sorbini Foundation and Institute of Nutrition, Metabolism and Diabetes. He received an honorarium from the US 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 Foundation. He received funding and travel support from The Canadian Society of Endocrinology and Metabolism to produce minicases for the CDA. His spouse (Alexandra Jenkins) is a director and partner of Glycemic Index Laboratories, and his sister (Caroline Brydson) received funding through a grant from the St. Michael’s Hospital Foundation to develop a cookbook for one of his studies. John Sievenpiper has received research support from CIHR, CDA, PSI Foundation, Banting & Best Diabetes Centre, CNS, ASN, Calorie Control Council, INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, The Coca-Cola Company (investigator initiated, unrestricted), Dr Pepper Snapple Group (investigator initiated, unrestricted), The Tate and Lyle Nutritional Research Fund at the University of Toronto, and The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto. He has received reimbursement of travel expenses, speaker fees and/or honoraria from CDA, CNS, University of Alabama at Birmingham, Oldways Preservaton Trust, NFI, Diabetes and Nutrition Study Group (DNSG) of the of the European Association for the Study of Diabetes (EASD), International Life Sciences Institute North America, Dr Pepper Snapple Group, Corn Refiners Association, World Sugar Research Organization, Dairy Farmers of Canada, Società Italiana di Nutrizione Umana (SINU), III World Congress of Public Health Nutrition, C3 Collaborating for Health, Sprim Brasil, The WhiteWave Foods Company, Rippe Lifestyle Institute, mdBriefCase Group, Federation of European Nutrition Societies (FENS), New York Academy of Sciences, International Diabetes Federation, American Heart Association (AHA), ASN, FoodMinds LLC, Memac Ogilvy & Mather LLC, Pulse Canada, PepsiCo, BCFN Foundation, The Ginger Network and Dietitians of Canada. He has ad hoc consulting arrangements with Winston & Strawn LLP, Perkins Coie LLP and Tate & Lyle. He is a member of the European Fruit Juice Association Scientific Expert Panel. He is on the Clinical Practice Guidelines Expert Committees of the CDA, EASD and Canadian Cardiovascular Society, as well as an expert writing panel of the ASN. He serves as an unpaid scientific advisor for the Food, Nutrition, and Safety Program, and the Technical Committee on Carbohydrates of the International Life Sciences Institute North America. He is a member of the International Carbohydrate Quality Consortium, Executive Board Member of the DNSG of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of Unilever Canada. Arash Mirrahimi has received a research grant from CIHR. No other competing interests were declared.

© 2017 Canadian Medical Association or its licensors.

Figures

Figure 1:

Summary of evidence search and selection.

Figure 2:

Relation between intake of total sugars and incident type 2 diabetes (highest v. lowest level of intake). Pooled risk estimate is represented by the blue diamond. Values of I2 ≥ 50% indicate substantial heterogeneity., Values greater than 1.0 indicate an adverse association. CI = confidence interval, RR = risk ratio.

Figure 3:

Relation between intake of fructose and incident type 2 diabetes (highest v. lowest level of intake). Pooled risk estimate is represented by the blue diamond. Values of I2 ≥ 50% indicate substantial heterogeneity., Values greater than 1.0 indicate an adverse association. CI = confidence interval, RR = risk ratio.

Figure 4:

Relation between intake of sucrose and incident type 2 diabetes (highest v. lowest level of intake). Pooled risk estimate is represented by the blue diamond. Values of I2 ≥ 50% indicate substantial heterogeneity., Values greater than 1.0 indicate an adverse association. BMI = body mass index, CI = confidence interval, RR = risk ratio. *For Colditz and colleagues, the total number of participants with high and low BMI was 84 360.