03 Issues & Trends
Cereal Foods World, Vol. 63, No. 4
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Point: Glycemic Index—An Important but Oft Misunderstood Marker of Carbohydrate Quality
Effie Viguiliouk,1,2 Stephanie K. Nishi,1,2 Thomas M. S. Wolever,1–4 and John L. Sievenpiper1–5
1 Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
2 Toronto 3D Knowledge Synthesis and Clinical Trials Unit, Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, ON, Canada.
3 Division of Endocrinology and Metabolism, Department of Medicine, St. Michael’s Hospital, Toronto, ON, Canada.
4 Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, ON, Canada.
5 Corresponding author. Dr. John L. Sievenpiper, MD, PhD, FRCPC, St. Michael’s Hospital, #6138-61 Queen St E, Toronto, ON M5C 2T2, Canada. Tel: +1.416.867.3732; Fax: +1.416.867.7495; E-mail: firstname.lastname@example.org
The glycemic index (GI) is a measure of carbohydrate quality that is supported by many international health organizations for the management of chronic diseases and is included on food labels in several different countries to help consumers make healthier food choices. Despite its endorsement by various health and governmental organizations, the GI concept remains controversial. The aim of this article is to address the most recent criticisms of the GI related to its accuracy, precision, and role in cardiometabolic disease prevention and management. Many of the criticisms appear to stem from a misunderstanding of the GI and do not undermine the best evidence from prospective cohort studies and randomized controlled trials, which show important clinical and public health benefits of reducing the GI of the diet.
The glycemic index (GI) was developed more than 30 years ago as a way to classify carbohydrate-containing foods based on their potential to raise blood glucose (1) and is considered a measure of carbohydrate quality (2). Since its introduction, GI values have been reported for more than 2,000 individual foods (3), and many international health organizations have come to support the use of GI in the management of diabetes and cardiovascular disease (CVD), including Diabetes Canada (4), the Canadian Cardiovascular Society (CCS) (5), the American Diabetes Association (ADA) (6), Diabetes Australia (7,8), Diabetes UK (9), the European Association for the Study of Diabetes (EASD) (10), and the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) (11) (Table I). To help consumers make healthier food choices, the GI has also been successfully included on food labels in different countries, including Australia, New Zealand, the United Kingdom, and South Africa (12,13), and a proposal to introduce a GI symbol program for food labels in Canada has recently been made (14,15).
Glycemic Index Criticisms and Rebuttals
Despite its endorsement by various health and governmental organizations (4,5,7–10,13), the GI concept has remained controversial since its inception. Over the past few decades several criticisms regarding the methodology and applicability of GI in human health and disease have been debated (Table II). The most recent criticisms have focused on the accuracy and precision of the GI, which has brought into question the value of GI in nutrition labeling and dietary recommendations (16–19). In particular, GI has been criticized for having high intra- and interindividual variation in values, raising concerns about the potential to misclassify foods as being low (≤55 on the glucose scale), medium (56–69), or high (≥70) GI (18,20–22). Most of these concerns, however, are related to glycemic response and not GI, which are not the same thing (19,23). People have a glycemic response to consumption of foods, which is a property of an individual that substantially varies within and between individuals; foods have a GI value, which is a property of a food that is assessed in individuals (i.e., humans are the “assay”) and is reliable with the use of standardized methodology—namely the International Organization for Standardization (ISO 26642:2010) methodology (19,24).
These criticisms appear to stem, in part, from conflation of the variation in GI estimates within and between individuals with the GI within and between foods, the measurement of which is based on at least 2 tests of the reference food (glucose or white bread) in at least 10 individuals (19,23,24). A recent example of this common misinterpretation is seen in a study by Matthan et al. (18) in which the authors conclude there is “substantial variability in individual responses to GI value determinations, demonstrating that it is unlikely to be a good approach to guiding food choices.” Using the standard deviation (SD) data from this study (SD = 15.3, n = 63) (18) or the SD data from the most recent interlaboratory study (SD = 9, n = 10) (25) for the measurement of GI, the highest margin of error for classification (10.9 based on a t distribution) would be much smaller than the difference between the high-GI and low-GI categories (i.e., 70–55 = 15 on the glucose scale). The result would be a <1% chance of misclassification of a low-GI food as a high-GI food. In fact, the measurement error of GI as expressed by its coefficient of variation (CV) of 17% (25) would meet the allowable variation for macronutrients or fiber (based on a ±20% tolerance limit, in which the amount measured is permitted to vary by up to 20% of the amount declared on the food label) set out in the food labeling requirements of both the U.S. Food and Drug Administration (FDA) (26) and the Canadian Food Inspection Agency (CFIA) (17,19,27).
Many of the criticisms, therefore, appear to stem from a misunderstanding of GI. It is important to continue to address these misunderstandings in order for progress to be made in this area and to help consumers make better dietary choices for their health.
Glycemic Index and Health Outcomes
Another main source of debate has been over whether the GI concept has meaningful advantages in the prevention and management of cardiometabolic diseases. Individual “negative” studies have often been invoked as evidence that the GI concept does not improve outcomes. A recent example is the OmniCarb randomized clinical trial (28), in which a low-GI dietary pattern failed to show improvements in insulin sensitivity, lipid levels, or systolic blood pressure. The accompanying editorial took the study as providing sufficient evidence to conclude that the GI concept may not be relevant for heart health (29). It has been correctly pointed out that this randomized controlled trial may have failed to show the expected improvements due to its short duration (<5 weeks), focus on relatively healthy insulin-sensitive individuals, and higher drop-out rate in the high-GI comparator arm (30). It is also only one among many studies of GI and cardiometabolic outcomes—the majority of which have longer follow-up durations and include individuals with a range of cardiometabolic phenotypes.
Systematic reviews and meta-analyses of the highest quality evidence from prospective cohort studies and randomized controlled trials have reached the opposite conclusion. Evidence from the most recent pooled analyses of >20 prospective cohort studies, involving >600,000 participants with 4–25 years of follow-up, show high-GI dietary patterns are associated with significant increases in incident type 2 diabetes (31), CVD (32), and coronary heart disease (CHD), especially in women (33,34), and a nonsignificant increase in incident stroke (35) (Fig. 1). This observational evidence aligns with the evidence from randomized controlled trials (Fig. 2). The most recent systematic pooled analyses of >50 randomized controlled trials, involving >4,000 participants with 4–68 weeks of follow-up, show that low-GI diets reduce glycated blood proteins (HbA1c and fructosamine) in people with diabetes (36) by the equivalent of ~0.5% in HbA1c, an absolute reduction that is at the lower limit of efﬁcacy of most antihyperglycemic agents and exceeds the FDA threshold of 0.3% for the development of new antihyperglycemic agents. These reductions are in addition to protective effects on blood lipids (total cholesterol and the primary lipid target for cardiovascular disease prevention, LDL-C) (37) and weight maintenance (38) in people with and without diabetes and on blood pressure in people without diabetes (39), all without any adverse effects on other cardiometabolic risk factors. Thus, the totality of the highest level of evidence used to support clinical practice guidelines and public health policy shows that reducing GI may have meaningful benefits for the prevention and management of diabetes and CVD—a conclusion shared by international diabetes and heart association guidelines (4–6,9,27,28).
Other Lines of Evidence
The large body of evidence supporting a causal role of low-GI interventions in cardiometabolic disease prevention is strengthened further by an important biological analogy. The α-glucosidase inhibitor acarbose, an oral prandial agent that effectively converts the diet to a low-GI dietary pattern, provides compelling evidence of the ability of an intervention that lowers GI to improve hard clinical outcomes (2). Individual randomized controlled trials (40,41) and systematic reviews and meta-analyses of randomized controlled trials (42,43) have shown that acarbose reduces incident type 2 diabetes, hypertension, CVD, myocardial infarction, and stroke in people at risk for type 2 diabetes (40,41,43) and myocardial infarction and CVD in people with type 2 diabetes (42); these reductions correspond with improvements in glycemic control and blood pressure that are similar to those seen in low-GI interventions (36–43) and have estimates that overlap with those observed for the association of low-GI dietary patterns with the same clinical outcomes (i.e., the 95% CIs contain the reciprocal of the estimates for the associations of high-GI dietary patterns with type 2 diabetes, CHD, and stroke) (31–35).
There remains a need for more research to address the existing uncertainties regarding GI. The available studies have identified several limitations, including the incorrect use of methodology to measure GI and a failure to achieve large enough differences in GI (>15 on the glucose scale) between intervention and control arms in randomized trials. To help address these limitations, it is suggested that policy makers, grant committees, and journal editors enforce the use of standardized GI methodology in the design, conduct, and reporting of future intervention studies (5). Future trials should also consider the use of metabolically controlled (full or partial) designs, with the provision of key low-GI study foods to ensure sufficient differences in GI are achieved. Several longer term randomized trials conducted in individuals with diabetes have already taken this approach and have achieved large differences in GI that corresponded to significant improvements in cardiometabolic risk factors (44–46).
Overall, many of the criticisms of GI appear to stem from misunderstanding of its meaning and utility. GI is a property of food, the purpose of which is not to indicate what an individual’s glycemic response will be on any one eating occasion, but rather to indicate which carbohydrate-containing foods will produce, on average, relatively lower or higher responses (19). As such, many of the criticisms do not call into question the validity of GI or undermine the evidence from prospective cohort studies and randomized controlled trials that when taken together show important clinical and public health benefits of reducing the GI of the diet. The GI remains an important marker of carbohydrate quality that can be considered complementary to other markers of carbohydrate quality, such as dietary fiber, and food-based approaches, such as whole grains, dietary pulses, and fruit.
E. Viguiliouk was supported by a Toronto 3D Knowledge Synthesis and Clinical Trials Foundation Internship Award. S. K. Nishi was supported by a Banting and Best Diabetes Centre Novo Nordisk Studentship. J. L. Sievenpiper was supported by a PSI Graham Farquharson Knowledge Translation Fellowship, Diabetes Canada Clinician Scientist Award, CIHR INMD/CNS New Investigator Partnership Prize, and Banting & Best Diabetes Centre Sun Life Financial New Investigator Award.
No competing interests are declared by E. Viguiliouk and S. K. Nishi. T. M. S. Wolever is a part owner and the president of Glycemic Index Laboratories, Inc, Toronto, Canada. He has received consultant fees, honoraria, or travel funding from Diabetes Canada, Temasek Polytechnic, and the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes. J. L. Sievenpiper has received research support from the Canadian Institutes of health Research, Diabetes Canada, the PSI Foundation, Banting and Best Diabetes Centre, Canadian Nutrition Society, American Society for Nutrition, Calorie Control Council, INC International Nut and Dried Fruit Council Foundation, National Dried Fruit Trade Association, 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 the Calorie Control Council). He has received in-kind research support from the Almond Board of California, California Walnut Commission, American Peanut Council, Barilla, Unilever, Unico, Primo, Loblaw Companies, Quaker (PepsiCo), Kellogg Canada, and WhiteWave Foods. He has received travel support, speaker fees, and/or honoraria from Diabetes Canada, Canadian Nutrition Society, Mott’s LLP, Dairy Farmers of Canada, Sprim Brasil, WhiteWave Foods, Rippe Lifestyle, mdBriefcase, Alberta Milk, FoodMinds LLC, Memac Ogilvy & Mather LLC, PepsiCo, The Ginger Network LLC, International Sweeteners Association, Nestlé Nutrition Institute, Pulse Canada, Canadian Society for Endocrinology and Metabolism, Barilla Centre for Food and Nutrition Foundation, and GI Foundation. He has ad hoc consulting arrangements with Winston & Strawn LLP, Perkins Coie LLP, Tate & Lyle, and Wirtschaftliche Vereinigung Zucker e.V. He is a member of the European Fruit Juice Association Scientific Expert Panel. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes, Canadian Cardiovascular Society, and Canadian Obesity Network. He serves as an unpaid scientific advisor for the Food, Nutrition, and Safety Program and the Technical Committee on Carbohydrates of the International Life Science Institute North America. He is a member of the International Carbohydrate Quality Consortium, executive board member of the Diabetes and Nutrition Study Group of the European Association for the Study of Diabetes, and director of the Toronto 3D Knowledge Synthesis and Clinical Trials Foundation. His wife is an employee of Unilever Canada.
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