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  • The initial submission of this article was received on January 31st, 2018 and was peer-reviewed by 2 reviewers and the Academic Editor.
  • The Academic Editor made their initial decision on February 11th, 2018.
  • The first revision was submitted on February 20th, 2018 and was reviewed by the Academic Editor.
  • A further revision was submitted on February 27th, 2018 and was reviewed by the Academic Editor.
  • The article was Accepted by the Academic Editor on February 27th, 2018.

Version 0.3 (accepted)

· · Academic Editor


The authors have satisfactorily answered to the reviewers' and editor's issues.

Please fix the authors of the following reference when you receive the galley proof (before publication):

instead of Giacomo Z, et al.....(Giacomo is the first name...)
Zoppini G, Targher G, Chonchol M, et al.
Title and journal and other details are correct.

Version 0.2

· · Academic Editor

Minor Revisions

There are still some points to fix, and grammar is still not adequate. These points need to be well addressed and considered seriously if the authors aim at publication.

Abstract: Methods, 62,5% males, instead of male; Results: interquartile range (IQR) should be added into parentheses in each pertinent case. Example: (IQR: 260.6 - 400.9 μmol/L).Conclusions: serum lipids, instead of lipid.

Introduction and throughout the text: references should be in progressive number in the text. Instead, ref. 34 follows 9-11 and precedes 12,13. The order of references should be fixed. Following ref. 12,13: “the association between serum UA and b-cell function is still poorly understood” is smoother, and should substitute the current text.
“newly diagnosed T2DM patients, and whether …. remains undefined”, and nor "undefine".

Discussion: page 13 “With regards to the mechanism….”
Page 14: There is a study finding, and not “founding”
Page 15: After ref. 39, 40: “so” should be deleted.
The paragraph following Table 8, should be completely rephrased. A possibility is: “As shown in Table 8, within the obese cohort, insulin resistance was more evident than in the normal weight group, although the two phases of insulin secretion were more evident. These results are compatible with the hyperinsulinemic conditions that characterize insulin resistance states. However, consistent with our results, another study showed a greater potential in the recovery of islet function in part of the obese population (41).”
“Tardiness” should be substituted with “delay”

References are not conform (although the journal will help later).
Reference 41 is embedded in ref 40. Please fix.
Reference 43 is incomplete for authors and journal : Greco M, Chiefari E, Montalcini T, Accattato F, Costanzo FS et al. Early effects of a hypocaloric, mediterranean diet on laboratory parameters in obese individuals. Mediat Inflamm 2014, 2014:750860.
Please, fix and verify the entire list for incongruences.

Version 0.1 (original submission)

· · Academic Editor

Minor Revisions

Please, consider all the issues raised by the reviewers, and in particular address the point concerning BMI parameters in Asian population.
English editing should be also very seriously considered.

[# PeerJ Staff Note: It is PeerJ policy that additional references suggested during the peer-review process should only be included if the authors are in agreement that they are relevant and useful #]

Reviewer 1 ·

Basic reporting

The Authors present a paper, in which they evaluate the association between uric acid and beta cell function indexes. It is an up-to-date topic, since a lot of researchers are investigating this issue and the underpinning mechanisms.
In this paper, gender differences are not focused adequately, as this should implicate two distinct and separate analyses, showing a first table in which all data are included and successive tables containing data separated by gender. Therefore, the authors have two possibilities: a) change the title of the manuscript, and omit this issue, or b) reanalyze data accordingly.
English needs improvement.
Abstract: In the Methods section, part of the last sentence should be omitted (“and identified….”) as it is a conclusive remark. In the Results, first line: if UA is measured in μmol/L, this should be added. Also, please specify what are the numbers in parentheses.
Line 67: “Credence in UA as…” should be replaced by “The idea of UA as….”
Lines 75-76: Researches addressing this issue should be mentioned, with the addition of their references (and novelty of this study briefly reported in the discussion).
Jia L, Xing J, Ding Y, Shen Y, Shi X, et al. (2013) Hyperuricemia Causes Pancreatic b-Cell Death and Dysfunction through NF-kB Signaling Pathway. PLoSONE 8(10): e78284.
Robles-Cervantes JA, Ramos-Zavala MG, Gonzalez-Ortiz, et al. Relationship between serum concentration of uric acid and insulin secretion among adults with type 2 diabetes mellitus. Int J Endocrinol 2011; 2011:107904.
Tang W, Fu Q., Zhang Q, et al. The association between serum uric acid and residual b-cell function in type 2 diabetes. J Diabetes Res 2014; 2014:709691.
Ling Y, Li XM, Gu Q, Gao X. Correlation of serum uric acid and islet beta cell functions in female type 2 diabetics. Zhonghua Yi Xue Za Zhi 2012, 92:541-5.
Line 86: “untreated diabetes” is presumably “untreated type 2 diabetets”. Authors should mention how type 1 diabetes was excluded.
Lines 110-111: Are the authors sure that glucose was measured in plasma and insulin in serum? This implies the collection of two different blood tubes. This should be re-checked.
Line 210: “better” is not clear. Please specify.
Line 247: ref. 28 should be placed after “endothelial cells”.
Line 250: an appropriate reference should be indicated.
Line 254: It could be added “These results may be interpreted as due to differences between rodents and humans”.
Line 255: “obviously” should be omitted.
Line 258: the authors should speculate about potential molecular mechanisms by which UA affects insulin secretion and insulin resistance. For example, they could add the following: “As many studies have been undertaken to better understand the complex molecular mechanisms inducing insulin secretion and insulin resistance, including studies that address potential target genes and pathways (ref….), further investigations are necessary to delineate the molecular role of UA in this context”.
Arcidiacono B., Iiritano S., Chiefari E., et al. “Cooperation between HMGA1, PDX-1, and MafA is Essential for Glucose-Induced Inuslin Transcription in Pancreatic Beta Cells”. Front Endocrinol 5:237. (2015)
Ohneda K., Ee H., German M. “ Regulation of insulin gene transcription”, Seminars in cell & Developmental Biology, Vol. 11);. 227-23. (2000)
Chen CC, Wu JY, Chang CT, et al. “Levels of retinol-binding 4 and uric acid in patients with type 2 diabetes mellitus. Metabolism 58:1812-6 (2009)
Bianconcini A., Lupo A., Capone S., “ Transcriptional activity of the murine retinol-binding protein gene is regulated by a multiprotein complex containing HMGA1, p54 nrb/NonO, protein-associated splicing factor (PSF) and steroidogenic factor 1 (SF1)/liver receptor homologue 1 (LRH-1)”, Int J Biochem Cell Biol, vol.11; pp. 2189-203. (2009)
Zhang Y, Yamamoto T, Hisatome I, et al. Uric acid induces oxidative stress and growth inhibition by activation adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic beta cells. Mol Cell Endocrinol 2013; 375:89-96.
References should be implemented as suggested.

Experimental design

Gender differences should be properly addressed, unless this is not indicated in the title (see basic reporting).

Validity of the findings

The novelty of this study should be briefly addressed in the discussion, in the light of previous similar findings.


Basic reporting

Authors investigate the relationship between uric acid and insulin secretion and function. Authors should better address previous literature in the field, and novelty should be adequately discussed (see references below, which should be cited).
Robles-Cervantes JA, Ramos-Zavala MG, Gonzalez-Ortiz, et al. Relationship between serum concentration of uric acid and insulin secretion among adults with type 2 diabetes mellitus. Int J Endocrinol 2011; 2011:107904.
Jia L, Xing J, Ding Y, et al. Hyperuricemia causes pancreatic beta-cell death and dysfunction through NF-kB Signaling Pathway. PLoS ONE 2013, 8: e78284.
Methods and statistics
Why did authors use BMI criteria for Caucasian instead of Asia-Pacific WHO criteria? The study participants were from China; thus, it would be more proper to use Asian-Pacific BMI cut-off levels in statistic. Please redo do statistic using the Asian-Pacific WHO BMI criteria.
It is not clear if the participants were only diagnosed using 75g OGTT. Did participants were diagnosed under any other WHO criteria?
Line 264, there are no references concerning the important role of diet and weight loss in diabetes. References could include:
Greco M, Chiefari E, Montalcini T, et al. Early effects of a hypocaloric, mediterranean diet on laboratory parameters in obese individuals. Mediators of Inflammation 2014, 2014:750860.
Grams J, Garvey WT. Weight loss and the prevention and treatment of type 2 diabetes using lifestyle therapy, pharmacotherapy, and bariatric surgery:mechanism of action. Curr Obes Rep, 2015, 4:287-302.
English should be well checked all over the text for grammar and typo errors.

Experimental design

See Basic Reporting

Validity of the findings

Authors should point out in the introduction or in the discussion what is the novelty of this paper in consideration of previous similar reports.

Comments for the author

This manuscript requires additional analysis.

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