Diabetes Metab J.  2024 Jan;48(1):134-145. 10.4093/dmj.2022.0383.

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 SY
• Zhang WS
• Jiang CQ
• Jin YL
• Zhu T
• Zhu F
• Xu L

• KMID: 2551269
• DOI: http://doi.org/10.4093/dmj.2022.0383

Abstract

Background
Abnormal glucose metabolism is a risk factor for colorectal cancer (CRC). However, association of glycosylated hemoglobin (HbA1c) with CRC risk remains under-reported. We examined the association between glycemic indicators (HbA1c, fasting plasma glucose, fasting insulin, 2-hour glucose, 2-hour insulin, and homeostasis model of risk assessment-insulin resistance index) and CRC risk using prospective analysis and meta-analysis.
Methods
Participants (n=1,915) from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Substudy were included. CRC events were identified through record linkage. Cox regression was used to assess the associations of glycemic indicators with CRC risk. A meta-analysis was performed to investigate the association between HbA1c and CRC risk.
Results
During an average of 12.9 years follow-up (standard deviation, 2.8), 42 incident CRC cases occurred. After adjusting for potential confounders, the hazard ratio (95% confidence interval [CI]) of CRC for per % increment in HbA1c was 1.28 (95% CI, 1.01 to 1.63) in overall population, 1.51 (95% CI, 1.13 to 2.02) in women and 1.06 (95% CI, 0.68 to 1.68) in men. No significant association of other measures of glycemic indicators and baseline diabetes with CRC risk was found. Meta-analyses of 523,857 participants including our results showed that per % increment of HbA1c was associated with 13% higher risk of CRC, with the pooled risk ratio being 1.13 (95% CI, 1.01 to 1.27). Subgroupanalyses found stronger associations in women, colon cancer, Asians, and case-control studies.
Conclusion
Higher HbA1c was a significant predictor of CRC in the general population. Our findings shed light on the pathology of glucose metabolism and CRC, which warrants more in-depth investigation.

Keyword

Colorectal neoplasms; Insulin; Glucose; Glycated hemoglobin

Figure

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  Fig. 1. Association of baseline glycosylated hemoglobin with the risk of colorectal cancer on 1,915 participants followed up from 2006–2008 (baseline) to April 2021 in the Guangzhou Biobank Cohort Study. The squares indicate the adjusted hazard ratios (HRs) and the horizontal lines represent 95% confidence interval (CI). aAdjusting for age, sex, waist circumference, smoking, alcohol drinking, household annual income, education, physical activity, intake of vegetable and red meat, bP<0.05, cP<0.01.

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  Fig. 2. Association of baseline measures of glucose metabolism (2006–2008) with risk of colorectal cancer on participants of the Guangzhou Biobank Cohort Study follow-up until April 2021. Potential nonlinear relationships were examined using restricted cubic splines (three knots on 10th, 50th, and 90th), with hazard ratios (HRs) from Cox proportional hazard models. The HRs was adjusted for age, sex, waist circumference, smoking, alcohol drinking, household annual income, education, physical activity, intake of vegetable and red meat. (A) Glycosylated hemoglobin, (B) fasting plasma glucose, (C) 2-hour glucose, (D) fasting plasma insulin, (E) 2-hour insulin, (F) homeostasis model of risk assessment-insulin resistance (HOMA-IR). CI, confidence interval.

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  Fig. 3. Pooled effect sizes and 95% confidence intervals (CIs) of per % increment in glycosylated hemoglobin (HbA1c) on risk of colorectal cancer. Effect sizes and 95% CIs of individual study except Guangzhou Biobank Cohort Study (GBCS) were calculated using study-specific dose-response analysis. The pooled estimates were obtained by using a random effect model. The dots indicate the effect sizes of per % increment in HbA1c. The size of the square is proportional to the weight of individual study. The horizontal lines represent 95% CI. The diamond data markers indicate the pooled effect size. RR, risk ratio; CRC, colorectal cancer; CC, colon cancer; RC, rectal cancer.

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