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Glycemic Index in the Treatment of Diabetes: The Debate Continues

The glycemic index (GI) remains a promising yet controversial area of research. Controversy regarding the application of GI in the management of diabetes was recently reignited with the publication in Diabetes Care of a positive metaanalysis on low-glycemic index interventions in diabetes by Brand Miller and coworkers [1] and the negative editorial it received from Franz, the past co-chair of the American Diabetes Association working group on nutrition recommendations [2]. The merits and limitation of the GI concept have been debated since its introduction in 1981 by Jenkins and coworkers [3]. The debate has centered on the importance of carbohydrate quality versus quantity in medical nutrition therapy (MNT) for diabetes (Table 1). The GI can be considered as a measure of carbohydrate quality. It measures the postprandial glycemia raising potential of a single food by expressing the rise in glycemia in response to a 50 g available carbohydrate portion of that food as a percentage of the rise in glycemia in response to a 50 g available carbohydrate portion of a reference food (white bread or glucose) [3]. Proponents of giving priority to carbohydrate quality argue that GI is a robust measurement [4–7], predicts the relative glycemic response to mixed meals [5–7], is easy to implement and follow [8–10], results in consistent improvements in glycemic control when applied in people with diabetes [7,11–17], and shows consistency for a benefit of low-GI in the prevention and treatment of diabetes across the three main levels of evidence: epidemiology, clinical interventions, and basic science [13–17]. In contrast, the opponents that favor giving priority to carbohydrate quantity argue that GI is highly variable [18–20], not physiological [18,21], cannot reliably predict mixed meal responses [18–26], difficult to learn and follow [18,19,22,23], and has inconsistent effects on markers of glycemic control and other aspects of metabolic control in people with diabetes [18–20,22,23,27–29]. These opposing positions have been reflected in the nutrition recommendations of International diabetes organizations (Table 2). The American Diabetes Association (ADA) [30] in their most recent evidence based guidelines maintained their position that carbohydrate quantity is a more important consideration than quality, dismissing the value of the GI in diabetes therapy. In contrast, most other major international diabetes organizations have interpreted the available data differently, supporting the application of the GI concept in the management of diabetes in their most recent guidelines. These organizations include the Canadian Diabetes Association (CDA) [31], Diabetes Australia (DA) [32], Diabetes UK [33], and the European Association for the Study of Diabetes (EASD) [34]. One of the principal points of divergence between the ADA and the other international diabetes organizations has been the clinical utility of the GI. The recent meta-analysis by BrandMiller and coworkers [1] addresses this issue directly. It provides compelling evidence that there is a clear trend of outcome benefit. The low-glycemic index interventions decreased HbA1c by 0.43% units compared with high-glycemic index interventions [1]. Although modest, this reduction is comparable with the 0.5% unit reductions in HbA1c achieved typically with the -glucosidase inhibitor, acarbose [35]. But in the accompanying editorial, Franz [2] questioned the clinical significance of the reductions. She argued that when the metaanalysis results are viewed in the context of conventional MNT interventions, these interventions are more effective than low-GI interventions in improving glycemic control, as assessed by HbA1c [2]. This claim deserves closer inspection. Fundamental differences in the designs between the 7 randomized controlled trials of conventional MNT reviewed in the editorial [2,36,37] and the 14 studies of low-GI interventions included in the metaanalysis [1] obscure comparisons. First, the MNT interventions are heterogeneous. Some described using energy restriction [38], while others described using different combinations of energy restriction [39], carbohydrate counting [40], increased meal frequency [39,40], or physical activity [39,40] with the addition of non-nutritional interventions such as increased treatment intensity [39,41], multidisciplinary care [42], behavioral modification [38,40,42], group education [40], or blood glucose self-monitoring [38–40,42] to achieve reductions in