Reviewer's report
Title:Effect of apple cider vinegar on delayed gastric emptying in people with
type 1 diabetes mellitus
Version: 3Date:8 October 2007
Reviewer: Karen Jones
Reviewer's report:
This manuscript evaluates the effect of apple cider vinegar on the rate of gastric
emptying, measured by ultrasonography, in patients with type 1 diabetes mellitus
with previously diagnosed gastroparesis.
Major Compulsory Revisions
1.Abstract, Methods p2: how were the patients ‘blinded’? Surely they would be
able to tell the difference between drinks?
2.Methods; p 5, lines 8-9: How were these symptoms assessed/quantified?
3.Methods; p 5, line 11: “Seven of the subjects had neuropathy…” Please clarify
whether this relates to peripheral neuropathy. How many of the patients had
autonomic nerve dysfunction? If assessed, please quote mean scores # SEM.
4.Methods; p 5, lines 13-16: Were patients also excluded on the basis of
previous major abdominal surgery, history of severe cardiovascular disease,
hepatic disease, etc?
5.Methods; p 5, lines 18-19: Were patients taking medications with known
gastrointestinal side effects (e.g. tricyclic antidepressants, anticholinergic agents)
also excluded?
6.Methods; p 6, line 1: The authors must state how the fasting blood glucose
window of 3.5 – 9.0 mmol/L was achieved. Was insulin taken on the morning of
the gastric emptying study?
7.Methods; p7, lines 3-5: Please explain the need for four different ultrasound
machines. Please also state the state and country of manufacture for each.
Furthermore, please specify which software was used to analyse the data. What
is meant by “for every single calculation of GER, the same machine was used”?
8.Methods; p7, lines 9-10: Could the authors please address the effects of a
change in posture (sitting to supine) on the gastric emptying rate?
9.Methods: The authors have used a technique, used previously by their group,
which involves only 2 ultrasonographic measurements (at 15 min and at 90 min).
Could the authors please explain why they did not take more measurements (at
more frequent time intervals) and look at the change in gastric emptying over
time, rather than just a ratio?
10.Methods: The blood glucose concentration and insulin levels were not
measured throughout the study. In light of previous literature relating to the
reported effects of vinegar on postprandial glycaemia and insulinaemia, and
substantial evidence that changes in the blood glucose concentration have a
major effect on the gastric emptying rate, could the authors please explain why
this was not measured?
11.Methods: The authors refer to gastrointestinal symptoms and hypoglycaemic
events, yet didn’t evaluate these. Please explain.
12.Results: What was the blood glucose concentration (mean # SEM) at baseline
at each visit? Did these differ statistically between examination days?
13.Results: After the vinegar meal, the negative values for range and q1 infer
that the area at 90 min > the area at 15 min. How can this be explained?
14.Results; p 9: Where is Figure 2?
15.Discussion; p 9, lines 9-10: If the study design was based on the fact that one
patient ?spontaneously/via questionnaire reported fewer gastrointestinal
symptoms during long-term vinegar consumption, then patients in this study
should have been given gastrointestinal symptom questionnaires to complete on
a daily basis during their 2-week administration of water with vinegar.
16.Discussion; p 11, line 1: The authors should, preferably, have stated the mean
# SEM blood glucose concentration at baseline and whether these differed
between examination days.
17.Discussion, p 11, line 2: “no one of the patients reported any symptoms of
hypoglycaemia”, however, patients were not asked directly or via questionnaire
and this statement, therefore, rests on the reliance of self-reports.
18.Discussion; p 11, line 5-6: What is meant by the “release” of paracetamol?
Does this refer to dissolution? It is not the dissolution rate which renders the
paracetamol absorption technique unreliable, but rather the differing
pharmacokinetic properties, i.e. different rates of absorption due to variable
gastric emptying rates, hepatic first-pass effect, etc. This sentence would better
read: “The paracetamol method is dependent on the absorption of paracetamol
across the small intestine which makes this method unreliable, as the
pharmacokinetics of paracetamol vary within and between individuals
(reference)”.
19.Discussion; p 11: Would the authors like to comment on the beneficial effects
these findings may have in type 2 (insulin-resistant) diabetes mellitus,
specifically, the decrease in postprandial glucose excursions and the need,
therefore, for further studies?
20.Conclusion; p 11: The authors have stated that “vinegar added to meals may
unfortunately delay gastric emptying”, but should comment on the clinical
implications of this, e.g. “…with a potential for adverse hypoglycaemic events.”
Furthermore, the authors should comment on the importance of blood glucose
monitoring when refering to dosage reduction of short-acting insulin.
Minor Essential Revisions
1.Patients included in the study have been referred to as having
insulin-dependent diabetes mellitus in the manuscript, yet as type 1 in the title.
Please clarify, using the ADA classification, whether the patients were type 1, or
type 2 requiring insulin.
2.Background; p 3, lines 1-2: It is recommended that the authors include a
reference at the end of the first sentence to substantiate the prevalence of the
disease in Sweden.
3.Background; p 3, lines 8-10: While the relationship between the rate of gastric
emptying and gastrointestinal symptoms may be weak, it must also be
recognised that a previous study (Jones et al. 1995) has demonstrated a
significant relationship between these two variables, i.e. delayed gastric emptying
is associated with a greater number of upper gastrointestinal symptoms.
4.Methods; p 5, line 12: “Those with renal failure….” This should be defined e.g.
creatinine clearance < 10 ml/min.
5.Methods; p 5, lines 20-21: What are the effects of snuff use on gastric
emptying? Was the snuff use excessive in the two applicable patients?
6.Methods; p 6, lines 2-3: Were diarrhoea and constipation the only two
symptoms which postponed the examination (?nausea and vomiting)?
7.Results; p 6, lines 6-9: The authors have not actually stated what was given at
the first examination, i.e. reference meal + 200ml water?
8.Results; p 6, line 11: Was honey added to the apple cider vinegar and if so,
how much? Or is it a commercially available honey-flavoured product? Please
clarify.
9.Results; p 6, lines 14-16: Could the authors please clarify whether the total
volume of the water-vinegar solution was 230 ml or 200ml?
10.Results; p 6: Were the order of the two different treatments randomised?
11.Results; p 6: Could the authors please explain why patients consumed the
water without vinegar for only one week and the water with vinegar for two
weeks? During the two week period of water with vinegar, please clarify whether
the patients were prohibited from consuming any other vinegar or acetic
acid-containing products.
12.Discussion; p 9, line 13: A reference is required regarding “the opposite
effect”.
13.Figure 1; p 13: Should this read “ clinically diagnosed diabetic gastroparesis”
rather than “suspected”?
Discretionary Revisions:
1. GER should be defined initially and then this term may be used throughout.
2. The abbreviation, BMI, should be defined.
3.Methods; p 5, line 3 would better read: Patients were recruited from those
previously diagnosed with gastroparesis measured by a previously described and
standardised scintigraphic and real-time ultrasound method (reference) at the
Malmö University Hospital.
4.Methods; p 8, line 1: Already stated, please remove.
5.Methods; p8, lines 2-5: Please state the state and country of manufacture for
this software package. ?heading labelled Statistical Analysis for this subsection.
6.References: There are several referencing errors, namely, refs 6, 7, 10. Please
review and correct.
7.Overall: The grammar is poor in some areas and needs to be reviewed.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Effect of apple cider vinegar on delayed gastric emptying in people with
type 1 diabetes mellitus
Version: 3Date:8 October 2007
Reviewer: Karen Jones
Reviewer's report:
This manuscript evaluates the effect of apple cider vinegar on the rate of gastric
emptying, measured by ultrasonography, in patients with type 1 diabetes mellitus
with previously diagnosed gastroparesis.
Major Compulsory Revisions
1.Abstract, Methods p2: how were the patients ‘blinded’? Surely they would be
able to tell the difference between drinks?
2.Methods; p 5, lines 8-9: How were these symptoms assessed/quantified?
3.Methods; p 5, line 11: “Seven of the subjects had neuropathy…” Please clarify
whether this relates to peripheral neuropathy. How many of the patients had
autonomic nerve dysfunction? If assessed, please quote mean scores # SEM.
4.Methods; p 5, lines 13-16: Were patients also excluded on the basis of
previous major abdominal surgery, history of severe cardiovascular disease,
hepatic disease, etc?
5.Methods; p 5, lines 18-19: Were patients taking medications with known
gastrointestinal side effects (e.g. tricyclic antidepressants, anticholinergic agents)
also excluded?
6.Methods; p 6, line 1: The authors must state how the fasting blood glucose
window of 3.5 – 9.0 mmol/L was achieved. Was insulin taken on the morning of
the gastric emptying study?
7.Methods; p7, lines 3-5: Please explain the need for four different ultrasound
machines. Please also state the state and country of manufacture for each.
Furthermore, please specify which software was used to analyse the data. What
is meant by “for every single calculation of GER, the same machine was used”?
8.Methods; p7, lines 9-10: Could the authors please address the effects of a
change in posture (sitting to supine) on the gastric emptying rate?
9.Methods: The authors have used a technique, used previously by their group,
which involves only 2 ultrasonographic measurements (at 15 min and at 90 min).
Could the authors please explain why they did not take more measurements (at
more frequent time intervals) and look at the change in gastric emptying over
time, rather than just a ratio?
10.Methods: The blood glucose concentration and insulin levels were not
measured throughout the study. In light of previous literature relating to the
reported effects of vinegar on postprandial glycaemia and insulinaemia, and
substantial evidence that changes in the blood glucose concentration have a
major effect on the gastric emptying rate, could the authors please explain why
this was not measured?
11.Methods: The authors refer to gastrointestinal symptoms and hypoglycaemic
events, yet didn’t evaluate these. Please explain.
12.Results: What was the blood glucose concentration (mean # SEM) at baseline
at each visit? Did these differ statistically between examination days?
13.Results: After the vinegar meal, the negative values for range and q1 infer
that the area at 90 min > the area at 15 min. How can this be explained?
14.Results; p 9: Where is Figure 2?
15.Discussion; p 9, lines 9-10: If the study design was based on the fact that one
patient ?spontaneously/via questionnaire reported fewer gastrointestinal
symptoms during long-term vinegar consumption, then patients in this study
should have been given gastrointestinal symptom questionnaires to complete on
a daily basis during their 2-week administration of water with vinegar.
16.Discussion; p 11, line 1: The authors should, preferably, have stated the mean
# SEM blood glucose concentration at baseline and whether these differed
between examination days.
17.Discussion, p 11, line 2: “no one of the patients reported any symptoms of
hypoglycaemia”, however, patients were not asked directly or via questionnaire
and this statement, therefore, rests on the reliance of self-reports.
18.Discussion; p 11, line 5-6: What is meant by the “release” of paracetamol?
Does this refer to dissolution? It is not the dissolution rate which renders the
paracetamol absorption technique unreliable, but rather the differing
pharmacokinetic properties, i.e. different rates of absorption due to variable
gastric emptying rates, hepatic first-pass effect, etc. This sentence would better
read: “The paracetamol method is dependent on the absorption of paracetamol
across the small intestine which makes this method unreliable, as the
pharmacokinetics of paracetamol vary within and between individuals
(reference)”.
19.Discussion; p 11: Would the authors like to comment on the beneficial effects
these findings may have in type 2 (insulin-resistant) diabetes mellitus,
specifically, the decrease in postprandial glucose excursions and the need,
therefore, for further studies?
20.Conclusion; p 11: The authors have stated that “vinegar added to meals may
unfortunately delay gastric emptying”, but should comment on the clinical
implications of this, e.g. “…with a potential for adverse hypoglycaemic events.”
Furthermore, the authors should comment on the importance of blood glucose
monitoring when refering to dosage reduction of short-acting insulin.
Minor Essential Revisions
1.Patients included in the study have been referred to as having
insulin-dependent diabetes mellitus in the manuscript, yet as type 1 in the title.
Please clarify, using the ADA classification, whether the patients were type 1, or
type 2 requiring insulin.
2.Background; p 3, lines 1-2: It is recommended that the authors include a
reference at the end of the first sentence to substantiate the prevalence of the
disease in Sweden.
3.Background; p 3, lines 8-10: While the relationship between the rate of gastric
emptying and gastrointestinal symptoms may be weak, it must also be
recognised that a previous study (Jones et al. 1995) has demonstrated a
significant relationship between these two variables, i.e. delayed gastric emptying
is associated with a greater number of upper gastrointestinal symptoms.
4.Methods; p 5, line 12: “Those with renal failure….” This should be defined e.g.
creatinine clearance < 10 ml/min.
5.Methods; p 5, lines 20-21: What are the effects of snuff use on gastric
emptying? Was the snuff use excessive in the two applicable patients?
6.Methods; p 6, lines 2-3: Were diarrhoea and constipation the only two
symptoms which postponed the examination (?nausea and vomiting)?
7.Results; p 6, lines 6-9: The authors have not actually stated what was given at
the first examination, i.e. reference meal + 200ml water?
8.Results; p 6, line 11: Was honey added to the apple cider vinegar and if so,
how much? Or is it a commercially available honey-flavoured product? Please
clarify.
9.Results; p 6, lines 14-16: Could the authors please clarify whether the total
volume of the water-vinegar solution was 230 ml or 200ml?
10.Results; p 6: Were the order of the two different treatments randomised?
11.Results; p 6: Could the authors please explain why patients consumed the
water without vinegar for only one week and the water with vinegar for two
weeks? During the two week period of water with vinegar, please clarify whether
the patients were prohibited from consuming any other vinegar or acetic
acid-containing products.
12.Discussion; p 9, line 13: A reference is required regarding “the opposite
effect”.
13.Figure 1; p 13: Should this read “ clinically diagnosed diabetic gastroparesis”
rather than “suspected”?
Discretionary Revisions:
1. GER should be defined initially and then this term may be used throughout.
2. The abbreviation, BMI, should be defined.
3.Methods; p 5, line 3 would better read: Patients were recruited from those
previously diagnosed with gastroparesis measured by a previously described and
standardised scintigraphic and real-time ultrasound method (reference) at the
Malmö University Hospital.
4.Methods; p 8, line 1: Already stated, please remove.
5.Methods; p8, lines 2-5: Please state the state and country of manufacture for
this software package. ?heading labelled Statistical Analysis for this subsection.
6.References: There are several referencing errors, namely, refs 6, 7, 10. Please
review and correct.
7.Overall: The grammar is poor in some areas and needs to be reviewed.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
user
Reviewer's report
Title:Effect of apple cider vinegar on delayed gastric emptying in people with
type 1 diabetes mellitus
Version: 3Date:8 October 2007
Reviewer: Karen Jones
Reviewer's report:
This manuscript evaluates the effect of apple cider vinegar on the rate of gastric
emptying, measured by ultrasonography, in patients with type 1 diabetes mellitus
with previously diagnosed gastroparesis.
Major Compulsory Revisions
1.Abstract, Methods p2: how were the patients ‘blinded’? Surely they would be
able to tell the difference between drinks?
2.Methods; p 5, lines 8-9: How were these symptoms assessed/quantified?
3.Methods; p 5, line 11: “Seven of the subjects had neuropathy…” Please clarify
whether this relates to peripheral neuropathy. How many of the patients had
autonomic nerve dysfunction? If assessed, please quote mean scores # SEM.
4.Methods; p 5, lines 13-16: Were patients also excluded on the basis of
previous major abdominal surgery, history of severe cardiovascular disease,
hepatic disease, etc?
5.Methods; p 5, lines 18-19: Were patients taking medications with known
gastrointestinal side effects (e.g. tricyclic antidepressants, anticholinergic agents)
also excluded?
6.Methods; p 6, line 1: The authors must state how the fasting blood glucose
window of 3.5 – 9.0 mmol/L was achieved. Was insulin taken on the morning of
the gastric emptying study?
7.Methods; p7, lines 3-5: Please explain the need for four different ultrasound
machines. Please also state the state and country of manufacture for each.
Furthermore, please specify which software was used to analyse the data. What
is meant by “for every single calculation of GER, the same machine was used”?
8.Methods; p7, lines 9-10: Could the authors please address the effects of a
change in posture (sitting to supine) on the gastric emptying rate?
9.Methods: The authors have used a technique, used previously by their group,
which involves only 2 ultrasonographic measurements (at 15 min and at 90 min).
Could the authors please explain why they did not take more measurements (at
more frequent time intervals) and look at the change in gastric emptying over
time, rather than just a ratio?
10.Methods: The blood glucose concentration and insulin levels were not
measured throughout the study. In light of previous literature relating to the
reported effects of vinegar on postprandial glycaemia and insulinaemia, and
substantial evidence that changes in the blood glucose concentration have a
major effect on the gastric emptying rate, could the authors please explain why
this was not measured?
11.Methods: The authors refer to gastrointestinal symptoms and hypoglycaemic
events, yet didn’t evaluate these. Please explain.
12.Results: What was the blood glucose concentration (mean # SEM) at baseline
at each visit? Did these differ statistically between examination days?
13.Results: After the vinegar meal, the negative values for range and q1 infer
that the area at 90 min > the area at 15 min. How can this be explained?
14.Results; p 9: Where is Figure 2?
15.Discussion; p 9, lines 9-10: If the study design was based on the fact that one
patient ?spontaneously/via questionnaire reported fewer gastrointestinal
symptoms during long-term vinegar consumption, then patients in this study
should have been given gastrointestinal symptom questionnaires to complete on
a daily basis during their 2-week administration of water with vinegar.
16.Discussion; p 11, line 1: The authors should, preferably, have stated the mean
# SEM blood glucose concentration at baseline and whether these differed
between examination days.
17.Discussion, p 11, line 2: “no one of the patients reported any symptoms of
hypoglycaemia”, however, patients were not asked directly or via questionnaire
and this statement, therefore, rests on the reliance of self-reports.
18.Discussion; p 11, line 5-6: What is meant by the “release” of paracetamol?
Does this refer to dissolution? It is not the dissolution rate which renders the
paracetamol absorption technique unreliable, but rather the differing
pharmacokinetic properties, i.e. different rates of absorption due to variable
gastric emptying rates, hepatic first-pass effect, etc. This sentence would better
read: “The paracetamol method is dependent on the absorption of paracetamol
across the small intestine which makes this method unreliable, as the
pharmacokinetics of paracetamol vary within and between individuals
(reference)”.
19.Discussion; p 11: Would the authors like to comment on the beneficial effects
these findings may have in type 2 (insulin-resistant) diabetes mellitus,
specifically, the decrease in postprandial glucose excursions and the need,
therefore, for further studies?
20.Conclusion; p 11: The authors have stated that “vinegar added to meals may
unfortunately delay gastric emptying”, but should comment on the clinical
implications of this, e.g. “…with a potential for adverse hypoglycaemic events.”
Furthermore, the authors should comment on the importance of blood glucose
monitoring when refering to dosage reduction of short-acting insulin.
Minor Essential Revisions
1.Patients included in the study have been referred to as having
insulin-dependent diabetes mellitus in the manuscript, yet as type 1 in the title.
Please clarify, using the ADA classification, whether the patients were type 1, or
type 2 requiring insulin.
2.Background; p 3, lines 1-2: It is recommended that the authors include a
reference at the end of the first sentence to substantiate the prevalence of the
disease in Sweden.
3.Background; p 3, lines 8-10: While the relationship between the rate of gastric
emptying and gastrointestinal symptoms may be weak, it must also be
recognised that a previous study (Jones et al. 1995) has demonstrated a
significant relationship between these two variables, i.e. delayed gastric emptying
is associated with a greater number of upper gastrointestinal symptoms.
4.Methods; p 5, line 12: “Those with renal failure….” This should be defined e.g.
creatinine clearance < 10 ml/min.
5.Methods; p 5, lines 20-21: What are the effects of snuff use on gastric
emptying? Was the snuff use excessive in the two applicable patients?
6.Methods; p 6, lines 2-3: Were diarrhoea and constipation the only two
symptoms which postponed the examination (?nausea and vomiting)?
7.Results; p 6, lines 6-9: The authors have not actually stated what was given at
the first examination, i.e. reference meal + 200ml water?
8.Results; p 6, line 11: Was honey added to the apple cider vinegar and if so,
how much? Or is it a commercially available honey-flavoured product? Please
clarify.
9.Results; p 6, lines 14-16: Could the authors please clarify whether the total
volume of the water-vinegar solution was 230 ml or 200ml?
10.Results; p 6: Were the order of the two different treatments randomised?
11.Results; p 6: Could the authors please explain why patients consumed the
water without vinegar for only one week and the water with vinegar for two
weeks? During the two week period of water with vinegar, please clarify whether
the patients were prohibited from consuming any other vinegar or acetic
acid-containing products.
12.Discussion; p 9, line 13: A reference is required regarding “the opposite
effect”.
13.Figure 1; p 13: Should this read “ clinically diagnosed diabetic gastroparesis”
rather than “suspected”?
Discretionary Revisions:
1. GER should be defined initially and then this term may be used throughout.
2. The abbreviation, BMI, should be defined.
3.Methods; p 5, line 3 would better read: Patients were recruited from those
previously diagnosed with gastroparesis measured by a previously described and
standardised scintigraphic and real-time ultrasound method (reference) at the
Malmö University Hospital.
4.Methods; p 8, line 1: Already stated, please remove.
5.Methods; p8, lines 2-5: Please state the state and country of manufacture for
this software package. ?heading labelled Statistical Analysis for this subsection.
6.References: There are several referencing errors, namely, refs 6, 7, 10. Please
review and correct.
7.Overall: The grammar is poor in some areas and needs to be reviewed.
What next?: Unable to decide on acceptance or rejection until the authors have
responded to the major compulsory revisions
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
assistant