Commentary on association of glycemic index and glycemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality

The ongoing debate about the optimal types of carbohydrates for reducing the risk of type 2 diabetes and related conditions remains a central topic in medical and nutritional research. The ongoing uncertainty about whether glycemic index (GI) and glycemic load (GL) should be considered significant dietary factors in the prevention of chronic diseases in the general population. Understanding the relationship between dietary GI and GL and type 2 diabetes mellitus is important, especially in Asian populations where carbohydrate-rich diets are prevalent.

The meta-analysis published in The Lancet in 2019 extensively reviewed the impact of carbohydrate quality on health. It highlighted that while low GI and low GL diets are linked to a reduced incidence of diabetes, cardiovascular mortality, stroke mortality, and breast cancer incidence, these findings were accompanied by inconsistent benefits on overall mortality and the incidence of non-communicable diseases. The study also noted variable reductions in the risk for different health outcomes based on the quality of carbohydrate intake, particularly emphasizing the significant health benefits associated with high dietary fiber and whole grain intakes¹.

In 2024, a new meta-analysis was published in The Lancet Diabetes & Endocrinology, examining the associations between the GI and GL with major health outcomes such as the incidence of type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. The study analyzed large prospective cohorts with at least 100,000 participants and assessed the lowest and highest quantiles of GI and GL, as well as fiber and whole grain diets within these cohorts². The meta-analysis identified ten large cohorts from the Richard Doll Consortium and analyzed 48 studies examining the effects of GI and GL on the outcomes of interest.

The results are summarized in Table 1, showing a positive correlation between high GI/GL diets and the incidence of type 2 diabetes, cardiovascular disease, and diabetes-related cancers². Additionally, low GI/GL diets were associated with a reduced risk of diabetes, cardiovascular mortality, and all-cause mortality. The article also compared the effects of high fiber and whole grain intake on health outcomes with the effects of low GI/GL diets, providing a new perspective on the potential value of these dietary characteristics in preventing chronic diseases.

Recruiting large cohorts with a very high number of cases, this study enhances the reliability of its conclusions. It covers not only GI/GL but also fiber and whole grains, and is more comprehensive in many aspects, especially including the addition of cancer and all-cause mortality.

The Shanghai Women's Health Study (SWHS) observed that high dietary GI/GL significantly increased the risk of diabetes, with a multivariable-adjusted relative risk (RR) of 1.21 (95% CI, 1.03–1.43) for GI and 1.34 (95% CI, 1.13–1.58) for GL³. The Japan Public Health Center-based study (JPHC), found that the highest quintile of GI had an RR of 1.41 (95% CI, 1.23–1.62), and the highest quintile of GL had an RR of 1.28 (95% CI, 1.10–1.48)⁴. In comparison with all cohorts with RRs of 1.27 for high GI and 1.15 for high GL, the higher RRs observed in the SWHS and JPHC suggested that the relationship between dietary GI/GL and type 2 diabetes risk may be more pronounced in Asian populations, possibly due to a higher consumption of high-GI food such as white rice.

Besides the risk of diabetes, the risk of stroke and coronary heart disease (CAD) were also reported. The SWHS observed that higher dietary GI and GL significantly increased the risk of stroke, with a multivariable-adjusted relative risk of 1.19 (95% CI, 1.04–1.36) for GI and 1.27 (95% CI, 1.04–1.54) for GL⁵. Similarly, in the section of CAD, the SHWS and the Shanghai Men's Health Study (SMHS) observed that higher carbohydrate intakes and GL significantly increase the risk of coronary heart disease, with a multivariable-adjusted relative risk (RR) of 1.50 (95% CI: 1.08, 2.08) for carbohydrate intakes and 1.87 (95% confidence interval: 1.00, 3.53) for GL⁶. Furthermore, the JPHC, found that dietary fiber was inversely associated with all-cause mortality⁷. All of them have higher RRs compared with the results in The Lancet meta-analysis, probably due to Asian diets containing a relatively high amount of carbohydrates, with carbohydrates accounting for as much as 59% of the energy intake⁴. Moreover, for a given body mass index, Asian populations have higher levels of visceral fat and insulin resistance than do populations of European ancestry^{8, 9}. It is plausible that a high consumption of refined carbohydrates may be particularly detrimental for Asian populations.

Several limitations exist in these studies. A significant limitation is its reliance on self-reported dietary data, which can lead to inaccuracies due to misreporting and recall bias. We need more objective and precise methods of dietary assessment to ensure the validity and reliability. Additionally, the variability in GI and GL values based on factors such as food source, variety, and preparation methods can complicate the interpretation of results¹⁰. This complexity makes it challenging for the average consumer to apply these concepts practically, especially in the absence of GI and GL metrics on food labels. These insights suggest that focusing on food quality – such as the inclusion of high dietary fiber and whole grains – and overall dietary patterns may be more effective for public health guidance than relying on GI and GL values, which can be highly variable and context-dependent¹¹. Furthermore, the study's focus on observational data, while valuable, limits the ability to draw firm causal inferences, highlighting the need for more randomized controlled trials to verify these associations.

In the future, the next study may look at how to quantify aspects in clinical practice, such as the timing and portion size of dietary changes and their impact on postprandial blood glucose levels. There is also room for a more detailed understanding of the mechanisms involved, including the effects on free radicals and insulin resistance. High GI meals may initially elevate blood glucose and insulin levels but subsequently trigger insulin resistance, resulting in increased concentrations of free fatty acids¹².

To conclude, the meta-analysis conducted by Jenkins et al.² demonstrates that the clinical advantages of low GI diet are comparable to high-fiber, wholegrain diet. These findings support the inclusion of GI and GL as important markers of carbohydrate quality in dietary guidelines.