Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials

Abstract

Objective: To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy.

Design: Systematic review and meta-analysis of randomised controlled trials.

Data sources: Medline, Embase, and the Cochrane Library searched up to 13 May 2021.

Eligibility criteria for selecting studies: Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes.

Outcome and measures: The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)).

Data extraction and synthesis: Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence.

Results: 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision.

Conclusions: This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population.

Study registration: ClinicalTrials.gov NCT04045938.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from Diabetes Canada and the Diet, Digestive tract, and Disease Centre through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund for the submitted work. LC is a Mitacs-Elevate postdoctoral fellow jointly funded by the government of Canada and the Canadian Sugar Institute. She was previously employed as a casual clinical coordinator at INQUIS Clinical Research, Ltd (formerly Glycemic Index Laboratories, Inc), a contract research organisation. TAK has received research support from the Canadian Institutes of Health Research (CIHR), the International Life Science Institute (ILSI), and National Honey Board. He has been an invited speaker at the Calorie Control Council annual meeting for which he has received an honorarium. DJAJ has received research grants from Saskatchewan and Alberta Pulse Growers Associations, the Agricultural Bioproducts Innovation Programme through the Pulse Research Network, the Advanced Foods and Material Network, Loblaw Companies Ltd, Unilever Canada and Netherlands, Barilla, the Almond Board of California, Agriculture and Agri-food Canada, Pulse Canada, Kellogg's Company, Canada, Quaker Oats, Canada, Procter and Gamble Technical Centre Ltd, Bayer Consumer Care, Springfield, NJ, Pepsi/Quaker, International Nut and Dried Fruit Council (INC), Soy Foods Association of North America, 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, Soy Nutrition Institute (SNI), the Canola and Flax Councils of Canada, the Calorie Control Council, CIHR, the Canada Foundation for Innovation (CFI) and the Ontario Research Fund (ORF). He has received 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, WhiteWave Foods. He has been on the speaker's panel, served on the scientific advisory board and received travel support and honoraria from 2020 China Glycemic Index (GI) International Conference, Atlantic Pain Conference, Academy of Life Long Learning, 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, Epicure, Danone, Diet Quality Photo Navigation (DQPN), Better Therapeutics (FareWell), Verywell, True Health Initiative (THI), Heali AI Corp, Institute of Food Technologists (IFT), SNI, Herbalife Nutrition Institute (HNI), Saskatchewan and Alberta Pulse Growers Associations, Sanitarium Company, Orafti, the International Tree Nut Council Nutrition Research and Education Foundation, the Peanut Institute, Herbalife International, Pacific Health Laboratories, Nutritional Fundamentals for Health (NFH), Barilla, Metagenics, Bayer Consumer Care, Unilever Canada and Netherlands, Solae, Kellogg, Quaker Oats, Procter and Gamble, Abbott Laboratories, 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, Agri-Culture and Agri-Food Canada, the Canadian Agri-Food Policy Institute, Pulse Canada, the Soy Foods Association of North America, the Nutrition Foundation of Italy (NFI), Nutra-Source Diagnostics, the McDougall Programme, 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 (CDA). He is a member of the International Carbohydrate Quality Consortium (ICQC). 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, The Portfolio Diet for Cardiovascular Risk Reduction (Academic Press/Elsevier 2020 ISBN:978-0-12-810510-8) 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. GL reports non-financial conflicts of interest from Independent Nutrition Logic Ltd (UK), International Carbohydrate Quality Consortium (CA), EASD Nutrition Guidelines Committee (EU), and personal fees from Beneo Institute (DE) outside the submitted work. He is director and holds shares in Independent Nutrition Logic Ltd, a consultancy. He and his wife have benefited from research grants, travel funding, consultant fees, and honoraria from the American Association for the Advancement of Science (USA), the All Party Parliamentary Group for Diabetes (London, UK), Almond Board of California (USA), BENEO GmbH (DE), Biotechnology and Biosciences Research Council (UK), British Nutrition Foundation (UK), Calorie Control Council (USA), Cantox (CA), Colloides Naturel International (FR), Coca Cola (UK), Danisco (UK and Singapore), Diabetes Nutrition Study Group (EASD, EU), DiabetesUK (UK), Elsevier Inc. (USA), European Commission (EU), European Polyol Association (Brussels), Eureka (UK), Food and Agricultural Organisation (Rome), Granules India (Ind), General Mills (USA), Health Canada (CA), Institute of Food Research (UK), International Carbohydrate Quality Consortium (CA), Institute of Medicine (Washington, DC), International Life Sciences Institute (EU and USA), Life Sciences Research Office, FASEB (USA), Nutrition Society of Australia, Knights Fitness (UK), Leatherhead Food Research (UK), LitghterLife (UK), Matsutani (JPN), Medical Research Council (UK), MSL Group (UK), Porter Novelli (UK), Sudzuker (DE), Sugar Nutrition/WSRO (UK), Tate and Lyle (UK), The Food Group (USA), WeightWatchers (UK), Wiley-Blackwell (UK), and the World Health Organisation (Geneva). He and his wife Helen Livesey have benefited from services of the Royal Society of Medicine (UK), Sense Nutrition Consultancy Group (UK), Acumentia Bioscience Consultancy Group UK, and memberships of the Nutrition Society of Great Britain, The Association for Nutrition (UK), The American Nutrition Society and the Canadian Nutrition Society (CA). GL is a professional member of Diabetes UK, and a Fellow of the Royal Society of Medicine (UK). TMSW is part owner and employee of INQUIS Clinical Research, Ltd (formerly Glycemic Index Laboratories, Inc), a contract research organisation. DR is director of Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases at Merkur University Hospital, Zagreb, Croatia. He is the president of Croatian Society for Diabetes and Metabolic Disorders of Croatian Medical Association. He serves as an executive committee member of Croatian Endocrine Society, Croatian Society for Obesity and Croatian Society for Endocrine Oncology. He was a board member and secretary of International Diabetes Federation (IDF) Europe and currently he is the chair of the IDF Young Leaders in Diabetes Programme. He has served as an executive committee member of the Diabetes and Nutrition Study Group of EASD and currently he serves as an executive committee member of Diabetes and Cardiovascular Disease Study Group of EASD. He has served as principal investigator or co-investigator in clinical trials of AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi Aventis, Solvay, and Trophos. He has received travel support, speaker fees, and honoraria from advisory board engagements and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Belupo, Boehringer Ingelheim, Eli Lilly, Lifescan – Johnson and Johnson, International Sweeteners Association, Krka, Medtronic, Mediligo, Mylan, Novartis, Novo Nordisk, MSD, Merck Sharp and Dohme, Pfizer, Pliva, Roche, Salvus, Sandoz, Solvay, Sanofi Aventis, and Takeda. HK works as director of clinical research at the Physicians Committee for Responsible Medicine, a non-profit organisation that provides nutrition education and research. JS-S reports serving on the board of and receiving grant support through his institution from the INC and the Eroski Foundation. He reports serving on the executive committee of the Instituto Danone Spain. He reports receiving research support from the Instituto de Salud Carlos III, Spain; Ministerio de Educación y Ciencia, Spain; Departament de Salut Pública de la Generalitat de Catalunya, Catalonia, Spain; European Commission; California Walnut Commission, Sacramento, CA, USA; Patrimonio Comunal Olivarero, Spain; La Morella Nuts, Spain; and Borges SA, Spain. He reports receiving consulting fees or travel expenses from Danone, California Walnut Commission, Eroski Foundation, Instituto Danone—Spain, Nuts for Life, Australian Nut Industry Council, Nestlé, Abbot Laboratories, and Font Vella Lanjarón. He is on the Clinical Practice Guidelines Expert Committee of EASD, and served on the Scientific Committee of the Spanish Food and Safety Agency, and the Spanish Federation of the Scientific Societies of Food, Nutrition and Dietetics. He is a member of the ICQC and an executive board member of the DNSG of EASD. CWCK has received grants or research support from the Advanced Food Materials Network, Agriculture and Agri-Foods Canada (AAFC), 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 Ltd, the Peanut Institute, Pulse Canada, and Unilever. He has received 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, WhiteWave Foods/Danone. He has received travel support and honoraria from the Barilla, California Walnut Commission, Canola Council of Canada, General Mills, International Nut and Dried Fruit Council, International Pasta Organisation, Lantmannen, Loblaw Brands Ltd, Nutrition Foundation of Italy, Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate and Lyle, Unilever, and White Wave Foods/Danone. He has served on the scientific advisory board for the International Tree Nut Council, International Pasta Organisation, McCormick Science Institute, and Oldways Preservation Trust. He is a founding member of the ICQC, executive board member of the DNSG of EASD, is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of EASD and is a director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. JLS has received research support from the Canadian Foundation for Innovation, Ontario Research Fund, Province of Ontario Ministry of Research and Innovation and Science, CIHR, Diabetes Canada, PSI Foundation, Banting and Best Diabetes Centre (BBDC), ASN, INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, National Honey Board (the US. Department of Agriculture (USDA) honey “Checkoff” programme), ILSI, Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (the USDA soy “Checkoff” programme), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), and The Nutrition Trialists fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received in-kind food donations to support a randomised controlled trial from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, and Nutrartis. He has received travel support, speaker fees, and honoraria from Diabetes Canada, Dairy Farmers of Canada, FoodMinds LLC, International Sweeteners Association, Nestlé, Pulse Canada, Canadian Society for Endocrinology and Metabolism (CSEM), GI Foundation, Abbott, General Mills, Biofortis, ASN, Northern Ontario School of Medicine, INC Nutrition Research and Education Foundation, European Food Safety Authority (EFSA), Comité Européen des Fabricants de Sucre (CEFS), Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, and Physicians Committee for Responsible Medicine. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate and Lyle, Wirtschaftliche Vereinigung Zucker e.V., Danone, and INQUIS Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and former member of the SNI Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, EASD, Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid scientific adviser for the Food, Nutrition, and Safety Programme (FNSP) and the Technical Committee on Carbohydrates of ILSI North America. He is a member of the ICQC, executive board member of DNSG of EASD, and director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His wife is an employee of AB InBev. DL, AA, AC, SBM and AM declare no competing interests. There are no products in development or marketed products to declare.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Fig 1

Literature search and selection strategy. Apo B=apolipoprotein B; CRP=C reactive protein; DBP=diastolic blood pressure; GDM=gestational diabetes; GI=glycaemic index; GL=glycaemic load; HbA1c=glycated haemoglobin; HDL-C=high density lipoprotein cholesterol; LDL-C=low density lipoprotein cholesterol; non-HDL-C=non-high density lipoprotein cholesterol; SBP=systolic blood pressure; SRMA=systematic review and meta-analysis; TG=triglycerides

Fig 2

Summary plot of the effect of low glycaemic index/glycaemic load dietary patterns on glycaemic control and cardiometabolic outcomes in randomised controlled trials in diabetes. Data are expressed as weighted mean differences with 95% confidence intervals using the generic inverse variance method modelled by random effects meta-analyses. To allow the pooled effect estimates for each end point to be displayed on the same axis, mean differences were transformed to standardised mean differences (SMDs). Pseudo-95% confidence intervals for each transformed SMD were derived directly from the original mean difference and 95% confidence intervals. Between study heterogeneity was assessed by the Cochran Q statistic, where P2 statistic, where I2 ≥50% is considered evidence of substantial heterogeneity.51 The grading of recommendations, assessment, development, and evaluation (GRADE) of randomised controlled trials are rated as “high” certainty of evidence and can be downgraded by five domains and upgraded. The filled black squares indicate downgrade or upgrade for each outcome. *For interpretation of the magnitude, we used the minimally important differences for each outcome and dose-response analyses to assess the importance of magnitude of our point estimate using the effect size categories according to new GRADE guidance (see supplemental methods and supplemental tables S5 and S10). †Not upgraded for dose-response (see supplemental table S10 for details). ‡Owing to the difference in directionality of high density lipoprotein cholesterol compared with the other outcomes with regards to signal for benefit or harm, the sign for the SMD was changed. §The interpretation of the magnitude of the effect was based on the positive linear dose-response gradient (see supplemental table S10 for details). To convert blood glucose to mg/dL, multiply by 18.02; LDL-C, non-HDL-C, and HDL-C to mg/dL, multiply by 38.67; to convert triglycerides to mg/dL, multiply by 88.57; to convert CRP to nmol/L, divide by 9.52. Apo B=apolipoprotein B; CI=confidence interval; CRP=C reactive protein; DBP=diastolic blood pressure; HbA1c=glycated haemoglobin; HDL-C=high density lipoprotein cholesterol; LDL-C=low density lipoprotein cholesterol; MD=mean difference; non-HDL-C=non-high density lipoprotein cholesterol; PMD=P value of the mean difference; PQ=P value of the heterogeneity; SBP=systolic blood pressure; SMD=standardised mean difference; TG=triglycerides