Insulin Resistance: The Increased Risk of Cancers
Round 1
Reviewer 1 Report (Previous Reviewer 1)
Comments and Suggestions for Authors
The revised version of the manuscript has considerably improved. However, the author should reorganize the text concept in Tables 2 and 3. In general, a table includes words or very concise sentences.
Author Response
Dear Reviewer
Thank you very much for your opinion and suggestion. According to your suggestion, Tables 2 and 3 are reorganized, they are shortened. Also, proofreading was done by professional translater/editor.
Reviewer 2 Report (Previous Reviewer 4)
Comments and Suggestions for Authors
The review has interest potential with an extensive bibliography. The authors have made a laudable effort at correcting multiple grammatical and syntactic errors in English, but it remains way under an acceptable level for publication.
Comments on the Quality of English Language
Despite corrections, this review still contains numerous grammatical and syntactic errors, like missing articles ("the" or "a") in front of names, lack of agreement between subject and verbs regarding singular or plural, passive expressions like "it was found that", "there are observed" , nonsensical sentences like lines 323-324, etc... These are two numerous for me to spend time correcting, the authors must find the help of a professional translator/editor more familiar with English before this paper can be reconsidered for publication.
Author Response
Dear Reviewer
Thank you very much for your opinion and suggestions. According to your suggestion, proofreading of manuscript was done by a professional translator/editor. Therefore, lines 323-324 are changed.
Round 2
Reviewer 2 Report (Previous Reviewer 4)
Comments and Suggestions for Authors
The author has made serious efforts to improve the writing of the manuscript.
Comments on the Quality of English Language
The quality has been improved.
Author Response
Dear Reviewer
Thank you very much for your opinion.
This manuscript is a resubmission of an earlier submission. The following is a list of the peer review reports and author responses from that submission.
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
This is a well-written review article regarding the interplay between insulin resistance and cancer. The manuscript is well-organized, but I would suggest the following:
- In lines 577-581 – Please reconsider to reorganize the text. This is not the conclusion of the previous data presented.
- Please add a reference in the 595 and 596 lines.
- Kindly explain all the abbreviations used in Figure 1 in its legend. Additionally, this Figure should benefit from typographical improvement to be more attractive to readers
- Please summarize the data presented in Section 3 (Insulin resistance) described in a Table for readers. The same suggestion for Insulin resistance and cancer mechanisms – Section 4
- At the end of the article, the author should discuss the limits and future perspectives of this study
- Carefully revise the references list according to the Current Oncology journal recommendations – e.g. references 46, 49 or 87.
Author Response
Dear Reviewer
Thank you very much for your review, opinion and suggestions. According to your suggestions:
1. In lines 577-581 (currently lines 681-686) text is recognized as below:
"In conclusion, insulin resistance and the components of the metabolic syndrome, such as dysglycemia and increased BMI are significantly associated with increased risk of thyroid cancer. However, obesity is involved in development of several cancers, the correlation between overweight or obesity and thyroid cancer risk remains controversial and still unknown. This is due to different results obtained in performed investigations. Based on investigations of leptin and its receptor, it was observed an association of PTC and DTC with obesity. It is also suggested that the increased prevalence of TC may be mainly associated with improved detection caused by used better diagnostic methods. Because obtained results are controversial, more metabolic studies are needed, as controlling metabolic disorders may reduce the risk of TC [154].
2. References for two sentences in the lines 595-597 (currently 707-709) is only [168].
3. All the abbreviations used in Figure 1 and its legend are explained. However, additional typographical improvement may be more attractive for readers, I think that it may cause more difficult Figure 1 for readers. Therefore, my idea was, that Figure 1 should be easy and therefore without additional "informations".
4. According to Reviewer's suggestion, there were added two tables: Table 2 "Pathogeny of insulin resistance" and Table 3 "Role of insulin resistance in cancer development"
5. At the end of article was added additional information, such as below:
"The last decades of medical research revealed dependence insulin resistance and cancer. Patients diagnosed with insulin resistance and its syndromes, have a higher risk for developing cancer as compared to general population. Unfortunately, as mentioned above, molecular mechanisms for these associations are not fully understood and many aspects of this dependence remains unknown. Because hyperinsulinemia, due to insulin resistance, plays an important role in the neoplastic transformation, therefore, understanding these mechanisms may be a novel diagnostic and therapeutic strategies in patients with hyperinsulinemia. To note, obesity and T2DM, which prevalence increases worldwide, are associated with IR. In future work is needed to investigate disorders in insulin/IGFs signaling pathways. Blocking these pathways may be a potential anti-cancer therapy".
6. Reference list is according to the MDPI journals recomendations.
Reviewer 2 Report
Comments and Suggestions for Authors
This review manuscript encapsulates the key findings and insights:
Prevalence of Insulin Resistance in Cancer Patients: Meta-analyses have substantiated that insulin resistance is frequently diagnosed in patients with various types of cancers. This highlights the pervasive presence of IR within the context of cancer and underlines its significance as a factor contributing to the disease.
Association with Other Metabolic Disturbances: The conclusion underscores the intricate web of metabolic disturbances linked to insulin resistance, including obesity, type 2 diabetes mellitus, metabolic syndrome, hyperinsulinemia, hyperglycemia, and dyslipidemia. Of particular note is the connection between hyperinsulinemia and increased cancer risk, as insulin itself is intimately involved in the progression of cancer.
Global Health Concern: The manuscript addresses the burgeoning global challenge posed by the rising prevalence of obesity and type 2 diabetes. These conditions, often driven by insulin resistance, are not only associated with various health risks but also significantly elevate the likelihood of developing cancer.
There are several questions that need to be answered.
Major comments
1. Complexity of the Topic: The manuscript explores a complex and multifaceted topic, including the relationship between insulin resistance, cancer, obesity, and diabetes. To ensure that the manuscript is comprehensive and accurate, a major revision may be necessary to refine and expand upon various aspects of the research.
2. Molecular Mechanisms: The manuscript acknowledges that the molecular mechanisms linking insulin resistance to cancer are not well-understood. This knowledge gap suggests that further research and discussion are needed to delve into this aspect, which may require significant revisions and additional data.
3. Clinical and Public Health Implications: While the manuscript touches on the clinical and public health implications of the findings, these areas could be further developed to provide practical guidance and recommendations. Expanding on these aspects may require a major revision.
4. Interdisciplinary Collaboration: Encouraging collaboration between experts in different fields (e.g., oncology, endocrinology, public health) and incorporating diverse perspectives could enhance the manuscript's quality. Coordinating such collaborative efforts may necessitate substantial revisions.
5. Future Research Directions: To strengthen the manuscript's contribution to the field, a more detailed discussion of future research directions is advisable. This could involve proposing specific research questions and potential areas for investigation, which may require significant revision.
Comments on the Quality of English Language
Minor editing of English language required
Author Response
Dear Reviewer
Please see the aatchment.
Author Response File: 
Author Response.pdf
Reviewer 3 Report
Comments and Suggestions for Authors
Thank you for the opportunity to review this interesting and comprehensive work. The strenghts lie in the thorough explanation of the underlying mechanisms of obesity and insulin resistance.
There are a few considerations though:
- the sentence „For example, up to 80% of patients with cancer of pancreas have T2D, when the cancer was diagnosed" at the beginning can be somewhat misleading. There are specific mechanisms for this entitiy that are described in detail later.
- even though the underlying mechanisms of insulin resistance are very interesting, the detailed description on abnormalities like Rabson-Mendenhall syndrome (RMS) might have missed the point in this otherwise very interesting review article, I would suggest focussing more on cancer and its mechanisms
- english is sometimes hard to read as there are tense mixes and shifts, furthermore the whole manuscript is a bit disorganized, first there is a part on obesity, then different tumor entities, then DM Type 2 and again different tumor entities -> I would recommend including diabetes in the description of the different tumor entities.
Comments on the Quality of English Language
I would suggest english editing
Author Response
Dear Reviewer
Please see the attachment.
Author Response File: Author Response.pdf
Reviewer 4 Report
Comments and Suggestions for Authors
This review is potentially interesting and contains an extensive bibliography, but is so poorly written and contains so many grammatical and other language errors that it is painful to review. I give examples on just the first page in the next section, but random checks show that it is a widespread problem in the manuscript. The authors should have it proofread by a native English speaker and resubmit.
Comments on the Quality of English Language
Line 13: Obesity and diabetes has been reported...: have been.
Line 24: ... elevated of blood glucose...: delete "of".
Line 26: ... levels, needs...: delete comma.
Line 27: ... can be determined to patients with cancer...: nonsensical.
Line 29: ... observations suggests that... : suggest.
Line 30: "International Agency for Research Cancer...": Research on Cancer.
Line 31: "Centers Disease Control": Centers for Disease Control and Prevention.
Line 31: ... reported, that... : delete comma.
Lines 32 and 33: Dependence... were confirmed...: was confirmed.
Line 34: ... excess weight also worsen... : worsens.
Line 39: have T2D, when... : had T2D (delete comma).
After this, I stopped...
Author Response
Dear Reviewer
Please see the attachment.
Author Response File: Author Response.pdf
