PONE-D-24-05539Magnitude, risk factors and economic impacts of diabetic emergencies in developing countries: A systematic reviewPLOS ONE

Dear Dr. Haile,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Two external referees identify merit and potential within the manuscript, but raised several concerns within the manuscript. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: No

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for submitting interesting paper.

I have the folliwing concerns.

1. Abstract

・Some words are misspelled. For example, sever is severe, and Diabetes Mullites is Diabetes Mellitus.

2. Introduction, Data Sources and search strategies

「We searched PubMed, COCRANE, MEDLINE, EMBASE…」

・COCRANE should be Cochrane. Make sure it is not a typo.

3. Materials and methods, Descriptions of the interested outcomes.

・What does the word “RBGL” mean? Please spell it in full when it first appears.

4. Results Prevalence of diabetic emergencies]

「Studies that carried out in China and Ethiopia has documented a range of prevalence rates or DKA episodes, from 3.8% to 73.4%, respectively (61, 74).」

4-1

・has→have

Studies that carried out in China and Ethiopia have documented a range of prevalence rates or DKA episodes, from 3.8% to 73.4%, respectively (61, 74).

4-2

・“The prevalence of diabetic ketoacidosis (DKA) in the study by Ahmed MM et al., referenced as ref 77, was 83%.I think the ratio will be 3.8% to 83%.

5. Table 1

5-1

・”Sever Hypoglycemia” should be “Severe Hypoglycemia”.

5-2

・Cross sectional is described in multiple ways, so please unify.

5-3

The items I noticed are only a small part of the critical errors. The author should thoroughly review and correct the entire content.

・The studies included in this table have such varying definitions that they cannot be compared. Particularly, prevalence should be reconsidered.

〇Prevalence and Incidence

For example,

・The ref 59 Edo study, focuses on prevalence(58%).

・The ref.69 Abate study, focuses on incidence(0.9%).

・The ref.61 Negera study likely focuses on prevalence（73.4%).

・The ref.74 Li J study, on the other hand, deals with incidence(3.8%).

〇Different definition of Prevalence

・The ref.67 Gebre B study explores the prevalence of diabetes complications among patients with diabetes mellitus.The 61 Negera study specifically looks at the prevalence of diabetes complications among patients with DKA, HHS, and hypoglycemia.

・The ref.20 SarfoKantanka study focuses on the prevalence of diabetes complications among patients with DKA, HHS, hyperglycemia and hypoglycemia.

・However, the ref.77 Ahmed study focuses on the prevalence of diabetes complications among patients with DKA and HHS.

Therefore, these studies are not directly comparable due to their different approaches and definition. If the overall number is defined as different, it is natural that it is not possible to compare the diseases contained in it by proportion.

6. Discussion, Prevalence of diabetic emergencies

「The review encompassed 26 studies from Africa (n=14), Asia (n=5),and Mexico (n=1), revealing variations in DME prevalence both within and between countries in　the developing world, underscoring the considerable scope of the issue.」

・Wasn’t the number of the studies from Africa 20?

That's all for my comments. Thank you.

Reviewer #2: The study is a systematic review of diabetic emergencies in developing countries. In total around 40 studies were included, the majority from Africa. Assessments of prevalence of emergencies and costs are presented, and a large variability is noted on study outcomes between the studies. The study adresses an important topic, but should be revised regarding language, structure and interpretation.

Major:

1. The study uses an unspecific language with frequent bold statements without support from real numbers eg. ”significant”, ”high incidence”, ”increased”, ”hazardous implications”, ”inadequate”. All such statements should be revised with quantified evidence from the references used in these sentences. A good example where this is already done is in the first paragraph of the introduction ”lower overall disease burden by 5-10%”.

2. With respect to the research question of the study, it may not be fair to include studies from developing countries across the globe, as there may be substantial differences between different regions. A subgroupanalysis only including countries in a specific region could resolve this problem. This should at least be done examining outcomes only examining studies from Africa, where most studies were performed. Potential regional differences should also be further discussed in the study.

3. The current conclusion in the abstract is not drawn from the results in the study and must be revised (the conclusion of the manuscript is fair). Please consider who is the intended reader of this manuscript, descision makers? The large variability between studies prevents any strategic conclusion on policymaking. Which new studies should be conducted, and where? What interventions could reduce emergencies, and how should these interventions be tested? What does the estimated costs mean for the current treatment strategies, would it be cheaper to treat diabetes more effectively? These aspecst are currently not discussed sufficiently.

Minor:

1. There are some places where data is unclear. Eg the summary of the 26 studies is detailed but only adds up to 20 studies. All numbers must be doubble checked.

2. The cost of emergencies is estimated around 200 dollars. This is a quite normal anual medication cost for any patient in a western country, and is from this perspective not considered high. Therefore, some context must be provided for this number to make any sense. What is the annual income in these countries, what proportion of healthcare costs does this constitute?

3. Hard numbers on the diabetesrelated mortalities in developing countries could further support the importance of this study.

4. Information regarding the current state of diabetes treatment in these regions is not discussed. CGM is meantioned, but is the mesuring of glucose in patients available at all for these individuals? What proportion have access to diabetes medications, and what proportion can measure glucose or ketones them selves in any way?

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Reviewer #1: No

Reviewer #2: No

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PONE-D-24-05539R1Magnitude, risk factors and economic impacts of diabetic emergencies in developing countries: A systematic reviewPLOS ONE

Dear Dr. Haile,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel it has merit and may be suitable for publication after considering minor revisions from its current form. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Feb 05 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear authors, please make the following changes to the manuscript, particularly those enlisted by referee 2.

Here are some of my specific considerations: 

1. Across all text, consider using the term “adults living with diabetes” instead of "adults with DM" for clarity and consistency.

2. In the abstract, correct the typo in the phrase "Sever hypoglycemia" to "Severe hypoglycemia."

3. In the introduction section, in the line “Non-communicable diseases (NCDs) are expected to increase and surpass infectious diseases by 2030, according to predictions," specify the source of predictions—are they from the NCD risk collaboration or the GBD studies?

4. Conduct a thorough check for typos and extra spaces throughout the manuscript. Examples include “Diabetes Mullites” and “irrelevant conte," as well as "sever hypoglycemia."

5. Please revise and ensure that the citations adhere to PLOS ONE guidelines, as some citations do not include the journal name or the year of publication.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for responding to our comments.

The authors performed a systematic review to assess the magnitude, risk factors and economic impacts of diabetic emergencies in developing countries.

I think it has improved significantly after the initial revisions

I have several concerns.

【Minor comments】

1)(Introduction)

・The global incidence of diabetes is rising rapidly, posing a significant public health challenge, particularly in developing countries, which account for approximately 80% of the 537 million people living with diabetes worldwide as of 2021.

〇Please add the reference of the facts.

2)(Introduction)

〇The sentence 「it characterized by abnormally high or low blood sugar levels, are significant contributors to morbidity, mortality, and increased healthcare costs among adults with diabetes. For instance, diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) collectively account for up to 30% of diabetes-related hospital admissions in developing countries, with mortality rates ranging from 5% to 20% depending on the region and healthcare access.」 may be 「it is characterized by abnormally high or low blood sugar levels, are significant contributors to morbidity, mortality, and increased healthcare costs among adults with diabetes. For instance, diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) collectively account for up to 30% of diabetes-related hospital admissions in developing countries, with mortality rates ranging from 5% to 20% depending on the region and healthcare access.」.

3)(Introduction)

〇The sentence「Even though diabetic emergencies are becoming more common in poor nations, there is a conspicuous Visible scarcity of paucity of thorough in-depth studies in this area, and the research that is currently available lacks statistical clarity and specificity.」may be [Even though diabetic emergencies are becoming more common in poor nations, there is a conspicuous visible scarcity of paucity of thorough in-depth studies in this area, and the research that is currently available lacks statistical clarity and specificity.].

4)(Results, Table 1)

The authors are calculating the prevalence, but the denominators differ.

・The ref.67 Gebre B study explores the prevalence of diabetes complications “among patients with diabetes mellitus.” The denominators are patients with diabetes mellitus.

・

However, the 61 Negera study specifically looks at the prevalence of diabetes complications “among patients with DKA, HHS, and hypoglycemia”. The denominators are not the patients with diabetes, but rather the patients with DKA, HHS, and hypoglycemia.

・The ref.20 SarfoKantanka study focuses on the prevalence of diabetes complications “among patients with DKA, HHS, hyperglycemia and hypoglycemia”. The denominators are not the patients with diabetes, but rather the patients with DKA, HHS, hyperglycemia, and hypoglycemia.

→〇If the groups of diseases included as subjects differ in each study, then each prevalence cannot be compared.

5)(Results, Table 4)

〇Please fill in the blanks in the Total score 'Yes (Y).'

6)Overall

〇Please review the document overall for minor English mistakes.

Example:

Descriptions of the Interested Outcomes

・Severe Hypoglycemia → Severe Hypoglycemia.

Reviewer #2: I think the manuscript is acceptable for publication. There are some minor spelling-errors/formatting errors which should be addressed before publication.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

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Magnitude, risk factors and economic impacts of diabetic emergencies in developing countries: A systematic review

PONE-D-24-05539R2

Dear Dr. Haile,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Neftali Eduardo Antonio-Villa, MD PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I want to congratulate the authors for their effort in addressing the reviewers' comments. All the considerations have been appropriately addressed, and I can proceed to recommend this manuscript for acceptance. 

Reviewers' comments: