In this article entitled, “Association of measures of glucose metabolism with colorectal cancer risk in older Chinese: a 13-year follow-up of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy and Meta-Analysis,” Wang et al. [4] investigated the correlations between various glycemic indicators (including glycosylated hemoglobin [HbA1c], fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and the risk of CRC using data from prospective analysis of the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy. Additionally, they conducted a meta-analysis to explore the association between HbA1c level and CRC risk. The study revealed significant findings: over an average follow-up period of 12.9 years, each percentage increment in HbA1c was linked to elevated CRC risk, while other glycemic indicators did not exhibit similar associations. This relationship was stronger among women. Interestingly, the latest metaanalysis reinforced this association, particularly among women and individuals in Asian countries. Given the potential impact of ethnic disparities on CRC risk, this study offers valuable insights into the CRC risk profile associated with glucose parameters among Asians. The authors’ robust support for the results and suggestions within the study were evident through analyses involving various confounders, subgroup analyses, and meta-analysis.

It would be intriguing to evaluate the association between the risk of CRC and HbA1c level according to diabetes status and duration. Epidemiological and biological evidence suggests that individuals diagnosed with diabetes may have an elevated risk of CRC [5]. Meta-analyses have reported consistent associations between type 2 diabetes mellitus and an increased risk of CRC, with risk ratios ranging from 1.2 to 1.4 [6,7]. The effects of diabetes itself on CRC risk need to be considered carefully, along with potential confounding factors. Therefore, a subanalysis by diabetes status is needed to examine the association between HbA1c level and CRC risk in individuals with and without diabetes. A meta-analysis revealed an elevated risk of CRC among individuals with type 2 diabetes mellitus who are receiving exogenous insulin [8]. It is crucial to consider the potential impact of insulin treatment on the results in the enrolled individuals with diabetes in this study. In addition, CRC shares many risk factors with glucose intolerance status, including low socioeconomic status, obesity, and smoking [9]. Despite adjustments for these factors, changes in these risk factors during the follow-up period may contribute to the development of CRC. National screening programs, lifestyle modifications, and dietary changes also may influence the incidence of CRC. Additionally, disparities in the quality and frequency of colonoscopy procedures could affect CRC incidence rates. In my view, it is imperative to consider these factors. CRC incidence in patients younger than 50 years, known as early-onset CRC, has been increasing, for reasons not fully understood [10]. Last, I anticipate that future studies will explore this young age group further.

I hope for further large prospective studies to reveal the association between CRC and glucose metabolism, leading to an individual approach for prevention. Moreover, in the context of the diabetes pandemic, this approach aligns closely with precision medicine principles.