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Diabetes and Nutrition The Role of Fructose, Sucrose, and High-fructose Corn Syrup in Diabetes Adrian I Cozma, HBSc 1,2 and John L Sievenpiper, MD, PhD 1,2,3 1. Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, Toronto, Ontario, Canada; 2. Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada; 3. Department of Pathology and Molecular Medicine, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada Abstract Concerns are growing regarding the role of dietary sugars in the development of obesity and cardiometabolic diseases, including diabetes. High-fructose corn syrup (HFCS) and sucrose are the most important dietary sweeteners. Both HFCS and sucrose have overlapping metabolic actions with adverse effects attributed to their fructose moiety. Ecologic studies have linked the rise in fructose availability with the increases in obesity and diabetes worldwide. This link has been largely underpinned by animal models and select human trials of fructose overfeeding at high levels of exposure. Although prospective cohort studies have shown significant associations comparing the highest with the lowest levels of intake sugar-sweetened beverages, these associations are small, do not hold at moderate levels of intake, and are subject to collinearity effects from related dietary and lifestyle factors. Most systematic reviews and meta-analyses from controlled feeding trials have shown that fructose- containing sugars in isocaloric exchange for other carbohydrates do not show evidence of harm and, in the case of fructose, may even have advantages for glycemic control, especially at small doses. Nevertheless, trials in which fructose-containing sugars supplement diets with excess energy have shown adverse effects, effects that appear more attributable to the excess energy than the sugar. There is no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects, although there is potentially cause for concern where fructose is provided at high doses or contributes excess energy to diets. Further investigation is warranted due to the significant knowledge gaps and weaknesses in existing research. Keywords Diabetes, fructose, high-fructose corn syrup, sucrose Disclosure: Adrian Cozma, HBSc, has no conflicts of interest to declare. John Sievenpiper, MD, PhD, has received research support from the Canadian Institutes of Health Research (CIHR), Calorie Control Council, The Coca-Cola Company (investigator initiated, unrestricted grant), Pulse Canada. He has received travel funding, speaker fees, and/or honoraria from the American Heart Association (AHA), American Society for Nutrition (ASN), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH), Canadian Diabetes Association (CDA), Calorie Control Council, Diabetes and Nutrition Study Group (DNSG) of the European Association for the Study of Diabetes (EASD), International Life Sciences Institute (ILSI) North America, ILSI Brazil, Abbott Laboratories, Pulse Canada, and The Coca-Cola Company. He is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of both the Canadian Diabetes Association (CDA) and European Association for the study of Diabetes (EASD), as well as the American Society for Nutrition (ASN) writing panel for a scientific statement on the metabolic and nutritional effects of fructose, sucrose, and high-fructose corn syrup. His wife is an employee of Unilever Canada. Acknowledgments: Aspects of this work were funded by a Canadian Institutes of Health Research (CIHR) Knowledge Synthesis Grant (funding reference number, 102078) and a research grant from the Calorie Control Council. Received: March 15, 2013 Accepted: April 28, 2013 Citation: US Endocrinology 2013;9(2):128–38 Correspondence: John L Sievenpiper, MD, PhD, Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St Michael’s Hospital, #6137-61 Queen Street East, Toronto, ON, M5C 2T2, Canada. E: john.sievenpiper@utoronto.ca Support: The publication of this article was supported by The Coca-Cola Company. The views and opinions expressed are those of the authors. The total number of people with diabetes worldwide is projected to double by 2030. 1,2 Given the increasing prevalence of obesity, these figures probably underestimate the future prevalence of diabetes. The risk for developing type 2 diabetes mellitus (T2DM) and premature cardiovascular disease are strongly linked to the metabolic syndrome, a condition characterized by excess central adiposity, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, hypertension, and impaired glucose tolerance. 3 A number of dietary factors have been implicated in the development and progression of this cardiometabolic phenotype. Chief among them have been sugars containing fructose: fructose, sucrose, and high-fructose 128 corn syrup (HFCS). Since a temporal relationship was first demonstrated between the increasing availability of HFCS and the prevalence of overweight and obesity in the US nearly a decade ago, 4 a fructose-centric view of cardiometabolic diseases has emerged. We aim to review the scientific evidence supporting the role of fructose-containing sugars in the epidemics of diabetes and its related cardiometabolic complications. Current Dietary Advice Regarding Sugar Intake Various dietary guidelines have addressed sugars (see Table 1). Most have focused on the reduction of added fructose-containing sugars to © TOU C H ME D ICA L ME D IA 2013