Association of High-Risk Obstructive Sleep Apnea with Microvascular Complications in Adults with Type 1 Diabetes Mellitus: A Case–Control Study

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This manuscript investigates the association between high-risk obstructive sleep apnea (OSA) and vascular complications in adults with type 1 diabetes mellitus (T1DM). The authors conducted a cross-sectional case–control study using the modified Berlin Questionnaire (mBQ) to classify participants as high or low risk for OSA. They report that although the prevalence of high-risk OSA was similar between T1DM patients and controls, individuals with T1DM classified as high-risk for OSA had a significantly higher prevalence of vascular complications.

Overall, the manuscript addresses an important and relatively underexplored clinical question, particularly because most previous studies on OSA-related vascular complications involve type 2 diabetes rather than T1DM. However, some minor revisions could improve the manuscript.

1. The study is cross-sectional, which prevents causal inference.

The manuscript suggests that OSA may contribute to vascular complications, but the opposite relationship is also possible as vascular disease, autonomic neuropathy, obesity may increase OSA risk.

Therefore, the results should be interpreted as associations rather than causal relationships.

2. The regression models adjust for demographic and lifestyle factors but do not adjust for important diabetes-specific variables, such as:

• HbA1c
• diabetes duration
• insulin therapy modality
• glycemic variability.

These variables are strong predictors of vascular complications and could confound the association.

3. The manuscript states that neuropathy was diagnosed using clinical examination and symptoms, including Semmes–Weinstein monofilament testing. However, diagnostic criteria should be described more precisely to ensure reproducibility.

Author Response

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Reviewer 2 Report

Comments and Suggestions for Authors

This is a well‑written and clinically relevant study addressing an underexplored area: the relationship between obstructive sleep apnea (OSA) risk and vascular complications in adults with type 1 diabetes mellitus (T1DM). The manuscript is clearly structured, the rationale is well articulated, and the findings are potentially impactful for screening practices. The use of the modified Berlin Questionnaire (mBQ) is justified and supported by prior validation work.

Several areas would benefit from clarification, tightening of methodology, and more cautious interpretation of findings. Strengthening these aspects will improve rigor and transparency.

1. Clarify the rationale for using mBQ instead of objective sleep testing
2. Provide more detail on the control group selection
3. Address potential selection bias
4. Expand on the absence of diabetic nephropathy
5. Interpretation of macrovascular findings should be more cautious: The discussion should emphasize that the macrovascular signal is driven by very small numbers and may be unstable.
6. Clarify the temporal relationship between diabetes duration and OSA risk

Author Response

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Reviewer 3 Report

Comments and Suggestions for Authors

1. The title of the manuscript is “Association of High-Risk Obstructive Sleep Apnea with Vascular Complications in Adults with Type 1 2 Diabetes Mellitus: A Case–Control Study”. In Sleep Apnea Syndrome (SAS), there are Obstructive apnea syndrome (OSAS) and central sleep apnea (CSA). If the suthors want to keep the current title, central sleep apnea (CSA) should be included.
2. In Ref. 5, it should be changed to “Atkinson MA. The pathogenesis and natural history of type 1 diabetes. Cold Spring Harb Perspect Med. 2012;2(11):a007641.”
3. In Ref. 30, it should be changed to “Gentile S, Monda VM, Guarino G, Satta E, Chiarello M, Caccavale G, Mattera E, Marfella R, Strollo F. Obstructive Sleep Apnea and Type 2 Diabetes: An Update. J Clin Med. 2025;14(15):5574.”.
4. “(Qualtrics, Provo, UT, USA)” (lines 178-179) should be changed to “(Qualtrics, Provo, UT)”.
5. “BM Corp., Armonk, NY, USA)” (lies 242-243) should be changed to “BM Corp., Armonk, NY)”.

Author Response

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Author Response File: Author Response.pdf

Reviewer 4 Report

Comments and Suggestions for Authors

The introduction is too long. You should reduce it by half. For example : paragraph from 73 to 82 could be just a sentence added to other paragraphs. 

The methods. the composite outcome is very heterogenous and extremely disputable. 

The results: the low number of some complications makes the composite outcome very unreliable. You should analyze only the retinopathy and neuropathy separately. You should redo the results part. Also the "Sensitivity Analyses" is not quite ok. The 95%CI are way to large. And also were is the univariate analysis inside of the diabetes cohort of covariates, regarding the OSA risk. Redo and add.

The discussions and conclusions should be redone, after new, correct results.

Author Response

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Reviewer 5 Report

Comments and Suggestions for Authors

This is an interesting study demonstrating association of high-risk OSA with vascular
complications in adults with T1DM. The paper is well written, with a lot of interesting data, but
there are several recommendations that should be considered.
1. Authors should introduce the abbreviation at its first appearance in the text and use it
throughout the manuscript (e.g., OSA, T1DM, etc.)
2. The introduction provides a very detailed overview of the pathophysiology as well as the
technology of continuous glucose monitoring. It should be reformulated.
3. The aim of the study is clearly stated, but authors should indicate the hypothesis of the
present research.
4. How were the controls selected? Were they matched by age and gender?
5. The authors state that 3150 people were screened at the start of the study, but only 228 were
included in the analysis. Why were such a large number of respondents excluded?
6. High-risk OSA was identified in 18.6% of individuals with T1DM and 11.9% of controls;
however, this difference was not statistically significant. The authors are encouraged to
provide a possible explanation for the lack of a significant difference between the two
groups.
7. The clinical implications of the findings could be further emphasized.

Comments for author File: Comments.pdf

Author Response

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Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have addressed the previous concerns effectively, and the clarity of the revision has significantly improved.

Author Response

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Reviewer 4 Report

Comments and Suggestions for Authors

The authors made some superficial changes. From the top to bottom.The introductions is still too long.

As I previously stated the number of events is very low, especially macrovascular complications. Thus the analysis is very underpowered and unreliable. The composite outcome is basically made from retinopathy and neuropathy, meaning that there is no real "composite" outcome. 

So: you either eliminate the waste : macrovascular complications, and only refer to microvascular outcome (retinopathy, neuropathy), or I would recommend rejection.

The "sensitivity analysis" is not what it should be: a multivariable model. The authors aproach does not actually addresses the confounding. Also glycated hemoglobin should be evaluated as well regarding the OSA risk. So, do a proper sensitivity analysis

 

Author Response

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