Reviewer ’s report  
 
Title: Type 1 and Type 2 Diabetes in Celiac Disease: Prevalence and Effect on Clinical and  
Histological Presen tation  
 
Version: 0 Date: 06 Jun 2016  
 
Reviewer: Annalisa Schiepatti  
 
Reviewer's report:  
 
In this paper the Authors describe some interesting epidemiological and clinical aspects of type 1 
and type 2 diabetes in Finnish adult coeliac patients. The primary endpoint of this study is to 
evaluate the prevalence of type I and type II diabetes in coe liac Finnish adults and to compare 
the results with those in the Finnish general population. This part of the study is well planned and 
the results obtained are interesting. The second endpoint is to evaluate whether differences in the 
clinical, serologica l and histological parameters exist between coeliac disease patients with or 
without concomitant DM1 or DM2. As far as this second endpoint is concerned, I am afraid I 
have the following major concerns:  
 
 
 
- The Authors state that concomitant DM1 or DM predis pose coeliac patients to severe 
comorbidities and that DM1 coeliac patients have a worse adherence to GFD (as shown in Table 
3). My first concern is about the number of patients who developed a complication of CD (if 
any) and/or died (if any, and eventuall y their cause of death, related or unrelated to CD), to see 
whether concomitant DM1 or DM2 influence mortality of coeliac patients. There are no data 
about that in this paper and it seems quite strange that nobody died among 1358 patients. I am 
conscious t hat the retrospective nature of the study represents by itself a limitation, but data 
about mortality can be easily obtained also from a regularly updated database. The second great 
limitation of this study is the fact that no data about the histological r esponse to GFD are 
provided. Although a follow -up duodenal biopsy is not routinely performed in all the coeliac 
centres, this point could be of interest to see whether differences in the mucosal recovery 
between DM1 and DM2 coeliac patients exist. Moreover , data on the histological recovery 
would have been useful in those coeliac patients in whom EMA were not positive (in table 2 we 
can see that EMA are negative in 9% of the DM2 and coeliac group (2nd column) and in 12% of 
the CD group (3rd column).  
 
 
Minor concerns:  
- As far as the type of clinical presentation of CD is concerned, I suggest to use the distinction 
into "Classical", "non classical" and "silent/asymptomatic" coeliac disease, according to the Oslo 
definitions [ref. Ludvigsson et al, Gut 2013]  
 
- With respect to the time of diagnosis of coeliac disease, when the diagnosis of DM was done? 
(months, years after?)  
- Since we are dealing with diabetic patients, it is really a pity that no data about glicemic 
control, BMI, triglicerides, diabetes -related  complications (nephropathy, retinopathy, 
neuropathy) in DM1 and DM2 patients are provided, but the Authors are conscious of that and 
clearly state it in the discussion  
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required  in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please exp lain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assess ment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, conside ring the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
I declare I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wis h to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Type 1 and Type 2 Diabetes in Celiac Disease: Prevalence and Effect on Clinical and  
Histological Presen tation  
 
Version: 0 Date: 06 Jun 2016  
 
Reviewer: Annalisa Schiepatti  
 
Reviewer's report:  
 
In this paper the Authors describe some interesting epidemiological and clinical aspects of type 1 
and type 2 diabetes in Finnish adult coeliac patients. The primary endpoint of this study is to 
evaluate the prevalence of type I and type II diabetes in coe liac Finnish adults and to compare 
the results with those in the Finnish general population. This part of the study is well planned and 
the results obtained are interesting. The second endpoint is to evaluate whether differences in the 
clinical, serologica l and histological parameters exist between coeliac disease patients with or 
without concomitant DM1 or DM2. As far as this second endpoint is concerned, I am afraid I 
have the following major concerns:  
 
 
 
- The Authors state that concomitant DM1 or DM predis pose coeliac patients to severe 
comorbidities and that DM1 coeliac patients have a worse adherence to GFD (as shown in Table 
3). My first concern is about the number of patients who developed a complication of CD (if 
any) and/or died (if any, and eventuall y their cause of death, related or unrelated to CD), to see 
whether concomitant DM1 or DM2 influence mortality of coeliac patients. There are no data 
about that in this paper and it seems quite strange that nobody died among 1358 patients. I am 
conscious t hat the retrospective nature of the study represents by itself a limitation, but data 
about mortality can be easily obtained also from a regularly updated database. The second great 
limitation of this study is the fact that no data about the histological r esponse to GFD are 
provided. Although a follow -up duodenal biopsy is not routinely performed in all the coeliac 
centres, this point could be of interest to see whether differences in the mucosal recovery 
between DM1 and DM2 coeliac patients exist. Moreover , data on the histological recovery 
would have been useful in those coeliac patients in whom EMA were not positive (in table 2 we 
can see that EMA are negative in 9% of the DM2 and coeliac group (2nd column) and in 12% of 
the CD group (3rd column).  
 
 
Minor concerns:  
- As far as the type of clinical presentation of CD is concerned, I suggest to use the distinction 
into "Classical", "non classical" and "silent/asymptomatic" coeliac disease, according to the Oslo 
definitions [ref. Ludvigsson et al, Gut 2013]  
 
- With respect to the time of diagnosis of coeliac disease, when the diagnosis of DM was done? 
(months, years after?)  
- Since we are dealing with diabetic patients, it is really a pity that no data about glicemic 
control, BMI, triglicerides, diabetes -related  complications (nephropathy, retinopathy, 
neuropathy) in DM1 and DM2 patients are provided, but the Authors are conscious of that and 
clearly state it in the discussion  
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required  in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please exp lain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assess ment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, conside ring the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
I declare I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wis h to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Type 1 and Type 2 Diabetes in Celiac Disease: Prevalence and Effect on Clinical and  
Histological Presen tation  
 
Version: 0 Date: 06 Jun 2016  
 
Reviewer: Annalisa Schiepatti  
 
Reviewer's report:  
 
In this paper the Authors describe some interesting epidemiological and clinical aspects of type 1 
and type 2 diabetes in Finnish adult coeliac patients. The primary endpoint of this study is to 
evaluate the prevalence of type I and type II diabetes in coe liac Finnish adults and to compare 
the results with those in the Finnish general population. This part of the study is well planned and 
the results obtained are interesting. The second endpoint is to evaluate whether differences in the 
clinical, serologica l and histological parameters exist between coeliac disease patients with or 
without concomitant DM1 or DM2. As far as this second endpoint is concerned, I am afraid I 
have the following major concerns:  
 
 
 
- The Authors state that concomitant DM1 or DM predis pose coeliac patients to severe 
comorbidities and that DM1 coeliac patients have a worse adherence to GFD (as shown in Table 
3). My first concern is about the number of patients who developed a complication of CD (if 
any) and/or died (if any, and eventuall y their cause of death, related or unrelated to CD), to see 
whether concomitant DM1 or DM2 influence mortality of coeliac patients. There are no data 
about that in this paper and it seems quite strange that nobody died among 1358 patients. I am 
conscious t hat the retrospective nature of the study represents by itself a limitation, but data 
about mortality can be easily obtained also from a regularly updated database. The second great 
limitation of this study is the fact that no data about the histological r esponse to GFD are 
provided. Although a follow -up duodenal biopsy is not routinely performed in all the coeliac 
centres, this point could be of interest to see whether differences in the mucosal recovery 
between DM1 and DM2 coeliac patients exist. Moreover , data on the histological recovery 
would have been useful in those coeliac patients in whom EMA were not positive (in table 2 we 
can see that EMA are negative in 9% of the DM2 and coeliac group (2nd column) and in 12% of 
the CD group (3rd column).  
 
 
Minor concerns:  
- As far as the type of clinical presentation of CD is concerned, I suggest to use the distinction 
into "Classical", "non classical" and "silent/asymptomatic" coeliac disease, according to the Oslo 
definitions [ref. Ludvigsson et al, Gut 2013]  
 
- With respect to the time of diagnosis of coeliac disease, when the diagnosis of DM was done? 
(months, years after?)  
- Since we are dealing with diabetic patients, it is really a pity that no data about glicemic 
control, BMI, triglicerides, diabetes -related  complications (nephropathy, retinopathy, 
neuropathy) in DM1 and DM2 patients are provided, but the Authors are conscious of that and 
clearly state it in the discussion  
 
 
 
 
 
Are the methods appropriate and well described?  
If not, please specify what is required  in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please exp lain in your comments to the authors.  
 
No 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assess ment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
 
 
 
 
 
 
 
 
 
 
Declaration of competing interests  
Please complete a declaration of competing interests, conside ring the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  
If your reply is yes to any, please give details below.  
 
I declare I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wis h to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant