Title: Effect of Diabetes Mellitus Type 2 and Sulfonylurea on Colorectal Cancer Development:
A Case-Control Study
Version: 3 Date: 28 Aug 2024
Reviewer:  Panagiotis Halvatsiotis
Reviewer's report:
Congratulations for your work and your efforts to support with your data advanced knowledge
regarding possible burden of the antidiabetic treatment on colon cancer development. We
should always encourage investigators who orchestrate efforts and ideas to provide the
scientific community with new and significant information. I personally acknowledge that you
have contributed laboriously to define your objectives, but I have serious worries about the
methodology followed and the interpretation of your results. Noteworthy, the extensive analysis
of your data provided valuable information but there are some points that I would like to
comment on, and your response will be appreciated.
Comment 1
There is concrete knowledge that obesity is strongly related with both type 2 diabetes mellitus
and colon cancer occurrence. I am wondering if there are available data (BMI or WHR) of your
participants in order your results to be normalized for this parameter. Otherwise, you have to
commend about in the discussion section and to study limitations
Comment 2
You are referring several times in your manuscript the hypothesis that hyperinsulinemia may
contributes the tumor growth and I am also wondering if you can extract from the patient files
their fasting insulin levels or to calculate their HOMA Test indices in order to statistically
normalize your results to these  parameters.
Comment 3
Your study population seems to be older that the controls, therefore it would be advisable to
statistically evaluate and the median age of the participants, while there is an aging effect on
carcinogenesis.
Comment 4
According to Table 1 the cancer patients on sulfonylurea are  only 41 and 21 in the control group
respectively. Due to the very low participation of the studied criterion please inform us about
the power of the study.
Comment 5
In the conclusion section of your manuscript, you state that "Enhance screening for CRC may
be advisable, especially in sulfonylurea - treated patients....". I believe this statement should not
appear in your conclusion while you did not observe such a clear statistical  determination. This
statement should be incorporated in the discussion section where you should discuss possible
reasons for the different results between the adjusted and unadjusted model.
Title: Effect of Diabetes Mellitus Type 2 and Sulfonylurea on Colorectal Cancer Development:
A Case-Control Study
Version: 3 Date: 28 Aug 2024
Reviewer:  Panagiotis Halvatsiotis
Reviewer's report:
Congratulations for your work and your efforts to support with your data advanced knowledge
regarding possible burden of the antidiabetic treatment on colon cancer development. We
should always encourage investigators who orchestrate efforts and ideas to provide the
scientific community with new and significant information. I personally acknowledge that you
have contributed laboriously to define your objectives, but I have serious worries about the
methodology followed and the interpretation of your results. Noteworthy, the extensive analysis
of your data provided valuable information but there are some points that I would like to
comment on, and your response will be appreciated.
Comment 1
There is concrete knowledge that obesity is strongly related with both type 2 diabetes mellitus
and colon cancer occurrence. I am wondering if there are available data (BMI or WHR) of your
participants in order your results to be normalized for this parameter. Otherwise, you have to
commend about in the discussion section and to study limitations
Comment 2
You are referring several times in your manuscript the hypothesis that hyperinsulinemia may
contributes the tumor growth and I am also wondering if you can extract from the patient files
their fasting insulin levels or to calculate their HOMA Test indices in order to statistically
normalize your results to these  parameters.
Comment 3
Your study population seems to be older that the controls, therefore it would be advisable to
statistically evaluate and the median age of the participants, while there is an aging effect on
carcinogenesis.
Comment 4
According to Table 1 the cancer patients on sulfonylurea are  only 41 and 21 in the control group
respectively. Due to the very low participation of the studied criterion please inform us about
the power of the study.
Comment 5
In the conclusion section of your manuscript, you state that "Enhance screening for CRC may
be advisable, especially in sulfonylurea - treated patients....". I believe this statement should not
appear in your conclusion while you did not observe such a clear statistical  determination. This
statement should be incorporated in the discussion section where you should discuss possible
reasons for the different results between the adjusted and unadjusted model.
Please review this paper.
user
Title: Effect of Diabetes Mellitus Type 2 and Sulfonylurea on Colorectal Cancer Development:
A Case-Control Study
Version: 3 Date: 28 Aug 2024
Reviewer:  Panagiotis Halvatsiotis
Reviewer's report:
Congratulations for your work and your efforts to support with your data advanced knowledge
regarding possible burden of the antidiabetic treatment on colon cancer development. We
should always encourage investigators who orchestrate efforts and ideas to provide the
scientific community with new and significant information. I personally acknowledge that you
have contributed laboriously to define your objectives, but I have serious worries about the
methodology followed and the interpretation of your results. Noteworthy, the extensive analysis
of your data provided valuable information but there are some points that I would like to
comment on, and your response will be appreciated.
Comment 1
There is concrete knowledge that obesity is strongly related with both type 2 diabetes mellitus
and colon cancer occurrence. I am wondering if there are available data (BMI or WHR) of your
participants in order your results to be normalized for this parameter. Otherwise, you have to
commend about in the discussion section and to study limitations
Comment 2
You are referring several times in your manuscript the hypothesis that hyperinsulinemia may
contributes the tumor growth and I am also wondering if you can extract from the patient files
their fasting insulin levels or to calculate their HOMA Test indices in order to statistically
normalize your results to these  parameters.
Comment 3
Your study population seems to be older that the controls, therefore it would be advisable to
statistically evaluate and the median age of the participants, while there is an aging effect on
carcinogenesis.
Comment 4
According to Table 1 the cancer patients on sulfonylurea are  only 41 and 21 in the control group
respectively. Due to the very low participation of the studied criterion please inform us about
the power of the study.
Comment 5
In the conclusion section of your manuscript, you state that "Enhance screening for CRC may
be advisable, especially in sulfonylurea - treated patients....". I believe this statement should not
appear in your conclusion while you did not observe such a clear statistical  determination. This
statement should be incorporated in the discussion section where you should discuss possible
reasons for the different results between the adjusted and unadjusted model.
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