PONE-D-20-05586

The impact of ramadan fasting on glucose variability in type 2 diabetes mellitus patients

PLOS ONE

Dear Dr Tahapary,

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Othmar Moser

Academic Editor

PLOS ONE

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Additional Editor Comments (if provided):

Thank you for the good study. Please see the detailed comments by the reviewers, suggesting major revision that I am agreeing to.

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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: Partly

Reviewer #2: Partly

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

Reviewer #1: Yes

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: Yes

Reviewer #2: No

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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: Yes

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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: Ramadan is the 9th month of the Islamic lunar calendar, during which Muslims abstain from food intake between sunrise and sunset. Major changes to dietary patterns occur during Ramadan as meals are taken before dawn and immediately after sunset. In the present trial Harbuwono et al. compare glucose variability in patients with type 2 diabetes using CGMS during and after Ramadan fasting.

Thank you for the opportunity to review this interesting work. Following are some notes:

Please use 'subjects with type 2 diabetes' instead of 'type 2 diabetes subjects' throughout the manuscript.

L74: please add citations

L78: typing error – also

Design and ethics

Please use prospective longitudinal cohort study fort he study design. Comparative generally describes comparison of groups, which is not correct in this trial.

Did the participants give written informed consent before they were included in the trial?

Was the study apporved by the University or by a ethics committee oft he University? Please clarify and add the ethics number.

Was the trial registered in a registry for clinical trials (eg clinicaltrials.gov)? Please add information.

Subjects selection

Please describe exclusion criteria (kidney disease, severe liver disease) in more detail, based on lab measurements (ASAT, ALAT , eGFR,..).

Were patients with insulin or GLP-1 therapy also excluded?

Are there any limitation regarding HbA1c? Please clarify.

Anthropometry measurement

Please add information about blood pressure measurement.

Results

L163ff: Only eight subjects were included in the final analysis – please change also the baseline characteristics (table 1) to these eight subjects.

Table 1

Please add HbA1c in mmol/mol

OAD – oral antidiabetic drug

Glucose variability data

L177: the rate of hypoglycemia (p=0,25) were similiar in both groups – where are the numbers of hypoglemic events? Please add these values (in table 2)

L181 vs. Table 2: 74,2% IG above target in the text versus 72,4% in table 2, please clarify.

Table 2: please add number of subjects included in this analysis.

Please use mean IG instead of average IG

L189: ..the peak was found at 3PM, please check.

L191: please update the analysis for 8 patients.

L195: Is this the figure legend to figure 1?

Figure 1A:

Were there some differences statistically significant at diverse timepoints?

Figure 2:

Please change axis title to „energy intake“

Figure S1:

Baseline characteristics can only be assessed once in a trial, please remove at T2 (4 weeks after Ramadan).

Maybe it would be more correct to illustrate 4 time points in this figure, since the CGMS disconnection are again 2 independent time points.

Anthropometric data and laboratory data were also collected at timepoint 2, please include them in the results section.

Reviewer #2: Dante Saksono Harbuwono et al. present a paper on the impact of fasting during and after Ramadan in type 2 diabetes mellitus patients. The paper is well written and the data has been thoroughly analysed. The observational study used a continuous glucose monitoring system (CGMS) to assess glucose variability during and after Ramadan but the sample size is small with only 10 people.

There are some major issues to adress:

1. It should be clarified in the title as well as the abstract that the focus of this paper is on patients with type 2 diabetes on OADs not patients with GLP-1 receptor agonists or insulin.

2. Why were only 3 non-consecutive days of food consumption and activity recorded?

3. How would the authors explain the significantly higher intake of fibre at iftar compared to suhur?

4. The patients chosen for this study are low to moderate risk and had a relatively high HbA1c level. They spent the majority of the time during CGMS above the interstitial target glucose. The safety of Ramadan fasting measured by glucose variability was shown for this specific group. Studies to confirm the safety of Ramadan fasting for type 2 diabetes subjects with a lower HbA1c or more time in the interstitial target glucose range are still necessary.

5. The small sample size is making it difficult to categorize subgroups but differences due to gender would be interesting.

As well as some minor issues:

1. It should be specified whether the informed consent was attained in written or in verbal form.

2. In the introduction line 66 CGMS is described as a minimally invasive blood glucose examination, whereas in the following sentence it is clearly stated it measures interstitial glucose levels which correlate with blood glucose levels. Also "interstitial glucose" is unnecessarily repeated in brackets.

3. Information on the time when the patients took the medication (morning and/or evening) and daily dosage should be added.

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Reviewer #1: No

Reviewer #2: No

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The impact of ramadan fasting on glucose variability in type 2 diabetes mellitus patients on oral anti diabetic agents

PONE-D-20-05586R1

Dear Dr. Tahapary,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Dr Othmar Moser

Academic Editor

PLOS ONE

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

**********

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: (No Response)

Reviewer #2: Yes

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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 your changes. Only a little note on my part, please compare the p-value in line 187 with the p-value in table 2 - there is a small discrepancy.

Reviewer #2: All open comments by the reviewers have been properly addressed by the authors, the manuscript has improved.

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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