The impact of colectomy and chemotherapy on risk of type 2 diabetes onset in patients with colorectal cancer: Nationwide cohort study in Denmark

Reviewer #1 (Public Review):

Summary:
In this study, the authors set out to determine whether colorectal cancer surgery site (right, left, rectal) and chemotherapy impact the subsequent risk of developing T2DM in the Danish national health register.

Strengths:
- The research question is conceptually interesting
- The Danish national health register is a comprehensive health database
- The data analysis was thorough and appropriate
-The findings are interesting, and a little surprising that there was no impact of chemotherapy on the development of T2DM

Weaknesses:
- This is not a weakness as such, but in the discussion, I would consider adding some brief comment on the international generalizability of the findings - e.g. demographic make up of the Danish population health register and background rates of DM and obesity in this population with CRC compared to countries on other continents.
- A little more information would be helpful regarding how T2DM was diagnosed in the registry. If someone did develop transient hyperglycemia requiring DM medications during chemotherapy, would the investigators have been able to identify these people? Would they have been classified as T2DM based on filling a prescription for DM meds for a period of time? Also, did the authors have information regarding time to development of T2DM after surgery?
- In the adjusted Models, the authors did not adjust for cancer stage, even though cancer stage appears to be very different between the chemo and no chemo groups. It would be interesting to know if it affects the results if the model adjusted for cancer stage
- It would be worthwhile to report if mortality rates were different between the groups during follow up, and if the authors investigated whether perhaps differences in mortality rates led to specific groups living longer, and therefore having more time to develop DM

Overall, the authors achieved their aims, and the conclusions are supported by their results as reported.
The results are unlikely to significantly change patient treatment or T2DM screening in this population. With some additional information, as described above, the results would be of interest to the community.

Reviewer #2 (Public Review):

Summary: The study showed the impact of cancer treatment on new onset of diabetes among patients with colorectal cancer using the national database. Findings reported that individuals with rectal cancer without chemotherapy were less likely to develop diabetes but among other groups, treatment didn't show any impact on the development of diabetes. BMI still played a significant role in developing diabetes regardless of treatment types.

Strengths:
One of the strengths of this study is innovative findings about the prognosis of colorectal cancer treatment stratified by treatment types. Especially, as it examined the impact of treatment on the risk of new chronic disease after diagnosis, it became significant evidence that suggests practical insights in developing a proper monitoring system for patients with colorectal cancer and their outcomes after treatment and diagnosis. It is imperative for providers to guide patients and caregivers to prevent adverse outcomes like new onset of chronic disease based on BMI and types of treatment. The next strength is the national database. As the study used the national database, the generalizability is validated.

Weaknesses: Even though the study attempted to examine the impact of each treatment option, the dosage of chemotherapy and the types of chemotherapy were not able to be examined due to the data source.