Nordic dietary patterns and cardiometabolic outcomes : a systematic review and meta-analysis of prospective cohort studies and randomised controlled trials

Funding Information: AZ is a part-time research associate at INQUIS Clinical Research (formerly Glycemic Index Laboratories), a contract research organisation, and a consultant for the Glycemic Index Foundation. AJG has received consulting fees from Solo GI Nutrition and an honorarium from the Soy Nutrition Institute. LC was 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. TAK has received research support from the CIHR, the International Life Science Institute (ILSI) and the National Honey Board. He has been an invited speaker at the Calorie Control Council Annual Meeting for which he received an honorarium. EMC reports grants from the Natural Sciences and Engineering Research Council of Canada and the CIHR while this study was being conducted, has received research support from Lallemand Health Solutions and Ocean Spray, and has received consultant fees and speaker and travel support from Danone and Lallemand Health Solutions (all are outside this study). 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 the Croatian Society for Diabetes and Metabolic Disorders of the Croatian Medical Association. He serves as an Executive Committee member of the Croatian Endocrine Society, Croatian Society of Obesity and Croatian Society for Endocrine Oncology. He was a board member and secretary of IDF Europe and is currently the chair of the IDF Young Leaders in Diabetes (YLD) Programme. He has served as an Executive Committee member of the Diabetes and Nutrition Study Group of the EASD and currently serves as an Executive Committee member of the Diabetes and Cardiovascular Disease Study Group of the EASD. He has served as principal investigator or co-investigator in clinical trials for AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi Aventis, Solvay and Trophos. He has received travel support, speaker fees and honoraria for advisory board engagements and/or consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Belupo, Boehringer Ingelheim, Eli Lilly, LifeScan – Johnson & Johnson, the International Sweeteners Association, Krka, Medtronic, Mediligo, Mylan, Novartis, Novo Nordisk, MSD, Pfizer, Pliva, Roche, Salvus, Sandoz, Solvay, Sanofi Aventis and Takeda. HK is 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 International Nut and Dried Fruit Council (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; the Departament de Salut Pública de la Generalitat de Catalunya, Catalonia, Spain; the European Commission; the California Walnut Commission, USA; Patrimonio Comunal Olivarero, Spain; La Morella Nuts, Spain; and Borges, Spain. He reports receiving consulting fees or travel expenses from Danone, the California Walnut Commission, the Eroski Foundation, the Instituto Danone Spain, Nuts for Life, the Australian Nut Industry Council, Nestlé, Abbot and Font Vella y Lanjarón. He is on the Clinical Practice Guidelines Expert Committee of the EASD and served on the Scientific Committee of the Spanish Agency for Food Safety and Nutrition and the Spanish Federation of the Scientific Societies of Food, Nutrition and Dietetics. He is a member of the International Carbohydrate Quality Consortium (ICQC) and an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD. CWCK has received grants or research support from the Advanced Food and Materials Network, Agriculture and Agri-Food Canada (AAFC), the Almond Board of California, Barilla, the CIHR, the Canola Council of Canada, the International Nut and Dried Fruit Council, the International Tree Nut Council Nutrition Research and Education Foundation, Loblaw Brands, the Peanut Institute, Pulse Canada and Unilever. He has received in-kind research support from the Almond Board of California, Barilla, the California Walnut Commission, Kellogg Canada, Loblaw Brands, Nutrartis, Quaker (PepsiCo), the Peanut Institute, Primo, Unico, Unilever, WhiteWave Foods/Danone. He has received travel support and/or honoraria from Barilla, the California Walnut Commission, the Canola Council of Canada, General Mills, the International Nut and Dried Fruit Council, the International Pasta Organization, Lantmannen, Loblaw Brands, the Nutrition Foundation of Italy, the Oldways Preservation Trust, Paramount Farms, the Peanut Institute, Pulse Canada, Sun-Maid, Tate & 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 and an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD, is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the 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, the Ontario Research Fund, the Province of Ontario Ministry of Research, Innovation and Science, the CIHR, Diabetes Canada, the American Society for Nutrition (ASN), the International Nut and Dried Fruit Council Foundation, the National Honey Board (US Department of Agriculture [USDA] honey ‘Checkoff’ programme), the Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, the Quaker Oats Center of Excellence, the United Soybean Board (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 (established by the Alberta Pulse Growers), the Plant Protein Fund at the University of Toronto (which has received contributions from IFF) and the Nutrition Trialists Fund at the University of Toronto (established by an inaugural donation from the Calorie Control Council). He has received food donations to support RCTs from the Almond Board of California, the California Walnut Commission, the Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, WhiteWave Foods/Danone, Nutrartis and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from the ASN, Danone, Dairy Farmers of Canada, FoodMinds, Nestlé, Abbott, General Mills, the Comité Européen des Fabricants de Sucre (CEFS), Nutrition Communications, the International Food Information Council (IFIC), the Calorie Control Council and the International Glutamate Technical Committee. He has or has had ad hoc consulting arrangements with Perkins Coie, Tate & Lyle, Phynova and INQUIS Clinical Research. He is a member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, the EASD, the Canadian Cardiovascular Society and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Food, Nutrition, and Safety Program (FNSP) and the Carbohydrates Committee of the IAFNS. He is a member of the ICQC, an Executive Board Member of the Diabetes and Nutrition Study Group of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. PM, EV, SBM, VC, US, UR, MU, A-MA, KH and IT declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Funding Information: Open access funding provided by University of Eastern Finland (UEF) including Kuopio University Hospital. The Diabetes and Nutrition Study Group of the EASD commissioned this systematic review and meta-analysis and provided funding and logistical support for meetings as part of the development of the EASD clinical practice guidelines for nutrition therapy. This work was also supported by the Canadian Institutes of Health Research (CIHR; reference no. 129920) through the Canada-wide Human Nutrition Trialists’ Network (NTN). The Diet, Digestive tract, and Disease (3D) Centre, funded through the Canada Foundation for Innovation and the Ministry of Research and Innovation’s Ontario Research Fund, provided the infrastructure for the conduct of this work. PM was funded by a Connaught Fellowship, an Onassis Foundation Fellowship and a Peterborough KM Hunter Charitable Foundation Scholarship. AZ was funded by a Toronto3D Postdoctoral Fellowship Award and a Banting and Best Diabetes Centre (BBDC) Fellowship in Diabetes Care. AJG was funded by a Nora Martin Fellowship in Nutritional Sciences, the Banting & Best Diabetes Centre Tamarack Graduate Award in Diabetes Research, the Peterborough K. M. Hunter Charitable Foundation Graduate Award and an Ontario Graduate Scholarship. LC was funded by a Mitacs Elevate Postdoctoral Fellowship Award. TAK was funded by a Toronto 3D Postdoctoral Fellowship Award. EMC held the Lawson Family Chair in Microbiome Nutrition Research at the Lawson Centre for Child Nutrition, Temerty Faculty of Medicine, University of Toronto. JS-S is partially supported by the Catalan Institution for Research and Advanced Studies (ICREA) under the ICREA Acadèmia programme. JLS was funded by a PSI Graham Farquharson Knowledge Translation Fellowship, Canadian Diabetes Association Clinician Scientist Award, CIHR Institute of Nutrition, Metabolism and Diabetes (INMD)/Canadian Nutrition Society (CNS) New Investigator Partnership Prize and BBDC Sun Life Financial New Investigator Award. Publisher Copyright: © 2022, The Author(s).AIMS/HYPOTHESIS: Nordic dietary patterns that are high in healthy traditional Nordic foods may have a role in the prevention and management of diabetes. To inform the update of the EASD clinical practice guidelines for nutrition therapy, we conducted a systematic review and meta-analysis of Nordic dietary patterns and cardiometabolic outcomes. METHODS: We searched MEDLINE, EMBASE and The Cochrane Library from inception to 9 March 2021. We included prospective cohort studies and RCTs with a follow-up of ≥1 year and ≥3 weeks, respectively. Two independent reviewers extracted relevant data and assessed the risk of bias (Newcastle-Ottawa Scale and Cochrane risk of bias tool). The primary outcome was total CVD incidence in the prospective cohort studies and LDL-cholesterol in the RCTs. Secondary outcomes in the prospective cohort studies were CVD mortality, CHD incidence and mortality, stroke incidence and mortality, and type 2 diabetes incidence; in the RCTs, secondary outcomes were other established lipid targets (non-HDL-cholesterol, apolipoprotein B, HDL-cholesterol, triglycerides), markers of glycaemic control (HbA 1c, fasting glucose, fasting insulin), adiposity (body weight, BMI, waist circumference) and inflammation (C-reactive protein), and blood pressure (systolic and diastolic blood pressure). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: We included 15 unique prospective cohort studies (n=1,057,176, with 41,708 cardiovascular events and 13,121 diabetes cases) of people with diabetes for the assessment of cardiovascular outcomes or people without diabetes for the assessment of diabetes incidence, and six RCTs (n=717) in people with one or more risk factor for diabetes. In the prospective cohort studies, higher adherence to Nordic dietary patterns was associated with 'small important' reductions in the primary outcome, total CVD incidence (RR for highest vs lowest adherence: 0.93 [95% CI 0.88, 0.99], p=0.01; substantial heterogeneity: I 2=88%, p Q<0.001), and similar or greater reductions in the secondary outcomes of CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). Inverse dose-response gradients were seen for total CVD incidence, CVD mortality and incidence of CHD, stroke and type 2 diabetes (p<0.05). No studies assessed CHD or stroke mortality. In the RCTs, there were small important reductions in LDL-cholesterol (mean difference [MD] -0.26 mmol/l [95% CI -0.52, -0.00], p MD=0.05; substantial heterogeneity: I 2=89%, p Q<0.01), and 'small important' or greater reductions in the secondary outcomes of non-HDL-cholesterol, apolipoprotein B, insulin, body weight, BMI and systolic blood pressure (p