Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

Background: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality.
Methods: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689.
Findings: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets.
Interpretation: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain.
Funding: Banting and Best and the Karuna Foundation.
Competing Interests: Declaration of interests DJAJ reports research grants from the Soy Nutrition Institute and the Canadian Institutes of Health Research (CIHR); in-kind supplies for trials as a research support from the Almond Board of California, Walnut Council of California, the Peanut Institute, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (Pepsico), Pristine Gourmet, Bunge Limited, Kellogg Canada, and WhiteWave Foods; payment or honoraria for lectures or presentations from Nutritional Fundamentals for Health–Nutramedica, Saint Barnabas Medical Center Rutgers New Jersey Medical School, The University of Chicago, 2020 China Glycemic Index International Conference, Atlantic Pain Conference, Academy of Life Long Learning; and travel support from NUTS 2022 and the 40th International Symposium on Diabetes and Nutrition. DJAJ is a co-chair of the International Carbohydrate Quality Consortium (ICQC) and has been invited by the International Diabetes Federation to join the committee on diabetes treatment and to take the lead in writing the dietary guidelines for the treatment of diabetes. His wife, Alexandra L Jenkins, is a director and partner of INQUIS Clinical Research for the Food Industry; his two daughters, Wendy Jenkins and Amy Jenkins, have published a vegetarian book that promotes the use of the foods described here (Jenkins WM, Jenkins AE, Jenkins AL, Brydson C. The portfolio diet for cardiovascular disease risk reduction. London: Elsevier, 2019); 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. AJG reports travel support, honoraria, or both from Vinasoy and the Academy of Nutrition and Dietetics; and a CIHR fellowship. SL reports consulting payments and honoraria (or promises of the same) for scientific presentations or reviews at numerous venues, including (but not limited to) the National Institute of Health, Fred Hutchinson Cancer Center, University of Missouri, Harvard University, University of Buffalo, Universidade Federal de São Paulo, and Guangdong Provincial Hospital and Academy of Medical Science. SL also reports honoraria from Twin Digital Health; compensation for serving on the data safety and monitoring board for several trials, including the SELECT trial sponsored by Novo Nordisk; royalties from UpToDate; and an honorarium from the American Society for Nutrition for his duties as Associate Editor. VM reports grants from the CIHR. HCG holds the McMaster–Sanofi Population Health Institute Chair in Diabetes Research and Care. HCG reports research grants from Sanofi, Eli Lilly, AstraZeneca, Novo Nordisk, Merck, Abbott, Hanmi, and Boehringer Ingelheim; honoraria for speaking from Sanofi, Eli Lilly, AstraZeneca, Novo Nordisk, Zuellig, DKSH Pharma, and Jiangsu Hanson; and consulting fees from Abbott, Kowa Research Institute, Carbon Brand, and Biolinq. CWCK reports grants from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada, Almond Board of California, Barilla, CIHR, Canola Council of Canada, International Nut and Dried Fruit Council, International Tree Nut Council Research and Education Foundation, Loblaw Brands, the Peanut Institute, Pulse Canada, and Unilever; in-kind research support from the Almond Board of California, Barilla, California Walnut Commission, Kellogg Canada, Loblaw Companies, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, and WhiteWave Foods–Danone; travel support from the Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organization, Loblaw Brands, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & Lyle, Unilever, and White Wave Foods–Danone; and consulting fees from Lantmannen. CWCK has served on the scientific advisory board for the McCormick Science Institute and Oldways Preservation Trust; and is a founding member of the ICQC, Executive Board Member of the Diabetes and Nutrition Study Group, and Director of Glycemic Consulting and the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. JLS reports research grants from the CIHR, Canada Foundation for Innovation, Ontario Research Fund, American Society for Nutrition, International Nut and Dried Fruit Council Foundation, National Honey Board, Institute for the Advancement of Food and Nutrition Sciences, Pulse Canada, The United Soybean Board, The Tate and Lyle Nutritional Research Fund (University of Toronto), The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund established by the Alberta Pulse Growers (University of Toronto), Nutrition Trialists Network Fund established by an inaugural donation from the Calorie Control Council (University of Toronto), Diabetes Canada, and Quaker Oats Center of Excellence; in-kind research support from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever–Upfield, Unico–Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods–Danone, Nutrartis, and Dairy Farmers of Canada; and speaker fees, honoraria, or both from Dairy Farmers of Canada, FoodMinds, International Sweeteners Association, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council, Calorie Control Council, International Glutamate Technical Committee, Arab Beverages Assocation, and Phynova. JLS reports ad hoc consulting arrangements with Perkins Coie, Tate & Lyle, Danone, Inquis Clinical Research, and Brightseed; has served as a scientific board member of the European Fruit Juice Association and the Soy Nutrition Institute; is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the Study of Diabetes, Canadian Cardiovascular Society, and Obesity Canada–Canadian Association of Bariatric Physicians and Surgeons; is a member of the ICQC, Institute for the Advancement of Food and Nutrition Sciences, Canadian Nutrition Society; is executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes; and is director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of AB InBev. All other authors declare no competing interests. Where authors are identified as personnel of the International Agency for Research on Cancer or WHO, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer or WHO.
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