Reviewer ’s report  
 
Title: Sex hormone binding globulin as a valuable biochemical marker in predicting gestational 
diabetes mellitus  Manal A. Tawfeek1*, Eman M. Alfadhli2, Abdulfatah M. Alayoubi3 Hesham 
A. El -beshbishy4 and, Fawzia A. Habib5.  
 
Version: 0 Date: 08 Feb 2 016 
 
Reviewer: Kerstin Berntorp  
 
Reviewer's report:  
 
This study evaluates SHBG as a marker of GDM. The issue is of potential interest but the paper 
needs improvement on several points to justify publication. I am especially conc erned about the 
methodology and how the results are presented. Some important points are listed below. 
Comments refer to section and line since page numbers are missing.  
 
Material and Methods  
To rule out the possibility of a selection bias the patient material should be described in greater 
detail.  
1. Line 32 -43: In what way was the study prospective? At which time point was informed 
consent obtained and when was enrollment? Were women consecu tively enrolled? How 
about the controls? They were matched (according to Results line 28), but for what? How 
many women were eligible for the study to start with and how many were eventually 
excluded (some exclusions may not be obvious until later in pregn ancy, such as gestational 
hypertension and pre -eclampsia).  
2. Line 44 -47: Women were diagnosed using the IADPSG -criteria. Were all women offered an 
OGTT or only those who fulfilled certain criteria, such as risk factors or RBG cut -offs?  
3. Information on how glucose was analyzed is missing, by which method? Were samples sent 
to the lab for analysis? If so, what was the time frame between sampling and analysis? 
Separation, put on ice, addition of glucose stabilizers?  
4. Line 49 -58: Samples were divided into  two parts, one for biochemical analysis and the other 
was frozen. Which were the biochemical analyses? Cholesterol? RBG? Please detail. Is the 
SHBG analysis stable on frozen samples?  
 
 
Statistical analyses  
1. Line 10 -13: The Mann -Whitney and Chi -squared t ests are mentioned but seem not to be 
used according to the results.  
2. Line 19 -20: Odds ratios and 95% confidence interval for SHBG was calculated ………. by 
which method? Simple regression? Multivariable regression?  
 
Results  
1. Line 30 -32: Random plasma glu cose is mentioned but further down random blood glucose is 
mentioned (RBG). Was the measurement on blood or plasma?  
2. Line 32: The referred p -value 0.295 seems incorrect. According to Table 1 p = 0.001.  
3. Line 33 -36: Mean ± SD for SHBG are given and is s aid to be significantly higher for GDM 
than for non -GDM women. However, it was the other way around according to Figure 1. 
Was the p -value given in the figure based on T -test? Due to the wide SD a non -parametric 
test seems more appropriate to use. The figu re would be more informative if also the 
distribution is illustrated in the figure (for example mean 95% CI or median interquartile 
range).  
4. Line 37 -39: It is not clear why and when RBG was measured. Indeed figure 2 illustrates the 
distribution of SHBG over the whole glucose range, but since the diagnosis of GDM was 
based on either the 0, 1 -h or 2 -h glucose value (according to the IADPSG -criteria) the 
correlation between either of these values and SHBG seems more interesting.  
5. It is suggested that Tabl e 2 is omitted. If the authors think this information is important it 
can be mentioned in the text under the results and the relevance of the findings further 
commented on in the discussion.  
6. Line 40 -43: It seems like the figures given for women with the  lowest and the highest SHBG 
values in fact are identical to those given above for women with GDM and non -GDM. 
Therefore the information on "increased risk" does not make sense and there seems to be 
something wrong with the OR (95% CI) given, which certain ly not is significant. In 
addition, Table 3 is missing. A multivariable logistic regression analysis including important 
risk factors and SHBG would be of interest.  
7. Line 44 -49: The ROC -curve is nice. What were the positive and negative predictive values ? 
 
 
Discussion  
1. Line 5 -10: The findings of the present study are summarized but is confusing (see point 6 
above). The increased odds were independent of known risk factors (age, weight,BMI etc…. 
Does this refer to the missing Table 3????  
2. The above ment ioned paragraph is the only one discussing the results in relation to a number 
of other studies, more or less relevant for the present findings (SHBG in early pregnancy 
etc.). All results should be discussed and integrated in the text, not the least the in teresting 
findings based on the ROC -curve.  
Figures and Tables  
Legends are missing explaining abbreviations and the statistical test used.  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
No 
 
Does the work incl ude the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Unable to assess  
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain 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  
assessment 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  
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