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Optimal Glycaemic Control and the Reduced Risk of Colorectal Adenoma and Cancer in Patients With Diabetes
abstract
This abstract is available on the publisher's site.
Access this abstract nowOBJECTIVE
Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain.
DESIGN
Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up.
RESULTS
Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (Ptrend<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87).
CONCLUSION
Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.
Additional Info
Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study
Gut 2024 Apr 03;[EPub Ahead of Print], X Mao, KS Cheung, JT Tan, LY Mak, CH Lee, CL Chiang, HM Cheng, RW Hui, MF Yuen, WK Leung, WK SetoFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Colorectal cancer (CRC) incidence is increasing globally. In 2022, it was the third most diagnosed cancer and the second most common cause of cancer-related mortality worldwide.1 Diabetes is an established risk factor for CRC;2 however, it remains unclear whether glycaemic control would modulate subsequent risk of CRC as well as adenoma.
In a propensity score–matched analysis using electronic health record data from 88,468 Chinese patients with diabetes mellitus, Mao et al examined the dose–response and time-varying relationship between glycaemic control and risk of subsequent colorectal neoplasia. They concluded that optimal glycaemic control, defined as an HbA1c level <7%, was associated with a 28% reduced risk of incident colorectal cancer, particularly in the left colon, and a lower risk of any nonadvanced and advanced colonic adenoma. Importantly, as HbA1c levels increased, the risk of colorectal cancer was also increased in a stepwise fashion. Optimal glycaemic control at baseline as well as post baseline put the patients at the lowest risk.
Validations of these findings in other epidemiologic studies with diverse populations are warranted. Further investigations of the mechanisms linking diabetes with colorectal neoplasia, including the insulin-like growth factor axis, hyperinsulinaemia, inflammation, and impaired immunological surveillance3 are also critical.
As we move forward, it is crucial to reiterate the unmet need to develop effective, early, and precision-based prevention strategies for CRC in the expanding younger, diabetic population.4 This issue is especially pertinent for younger populations who are increasingly facing higher risks of CRC at earlier ages than previous generations.5 Ultimately, it is imperative to develop integrated approaches to prevent CRC and other major chronic diseases for which diabetes serves as a risk factor.
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