Title: The association of parity/live birth number with incident type 2 diabetes among women:
over 15 years of follow-up in The Tehran Lipid and Glucose Study
Version: 2 Date: 12 May 2021
Reviewer's report:
This is a population-based prospective study to investigate the association of parity/number of
live births with incidence of type 2 diabetes in a cohort of women who were residents of Tehran,
Iran. While the study is well designed and it is conducted in the frame-work of a well-known
population-based cohort from Middle-East with a long follow-up duration there are several
issues that must be noted:
Abstract
1. Line 4: Please delete the word region after Middle East.
2. Line 10: Please use the term parity/live birth number throughout the manuscript.
3. Lines 18:20: There’s no need to report the results of the age-adjusted model in the abstract.
Introduction
4. Line 7: Please change “Tehranian adults” to “adult residents of Tehran”. And combine with
the next sentence.
5. Line 18: Reporting the RR (95% CI) of a meta-analysis is too much information for
introduction and can be used in the discussion instead.
6. Line 18: Please correct to “meta-analyses”. The same for other instances in the manuscript.
7. Line 19: Please delete “(reference =0 or 1)”.
8. Lines 19-20: Please change “was found to have about...” to “was associated with about 40%
higher risk of incident T2DM”.
9. Line 21: Please correct to “meta-analyses”.
10. Page 4, line 1: Please connect the sentence about ethnicity to the previous sentence.
11. Page 4, line 6: The duration of follow-up is part of the results and should not be mentioned
in the introduction.
Methods:
12. Page 5, line 20: What do the authors mean by “singles”? Does this mean a single woman
with child has been excluded from the study? If yes, this is not correct. Please clarify.
13. Page 5, line 22: What does “not differentiable” mean? No blood samples or lab results?
Please clarify.
14. Page 6, line 3: How was this response rate calculated? It appears that it’s calculated as
2552/3313. But an additional 68+202 participants were excluded from the 3313 and then 491
were lost to follow-up. Please clarify.
15. Page 6, line 9: The name of the supplemental file should be corrected to “Questionnaire”.
16. Page 7, line 6: Please change to “more than 12 years of education and less than 12 years
of education”.
17. Page 7, lines 18-22: Please provide a reference for using restricted cubic splines while
considering that parity is a count (discrete) data. Moreover, please explain on what basis the
location and number of the knots were specified. It is important to check the fit of the models to
avoid overfitting. The number of knots should be decided in a way to not over fit the models and
to not force a curve to the data. Based on figure 1, it might be possible that with fewer knots the
non-linear association might not remain significant. Please explain why four knots were used
and provide the goodness of fit of the model.
18. Page 8, line 11: Please change to “which were previously investigated in the TLGS”.
Results:
19. Page 9, line 7: Please change to “HRs and 95% CI of the association of number of parity
and live births with incident T2DM...”.
20. Page 9, line 8: Please change to “each additional” instead of “each unit”.
21. Page 9, line 13: How was the P for trend calculated? Please explain in the statistical analysis
section.
22. Tables 2 and 3: Please provide the number of events/ total N per parity and number of live
birth groups.
23. Since separate analyses have been performed for the number of live birth, a descriptive of this
exposure should be provided so that the difference with parity becomes clear. What more does it
have to say compared to parity? If not much, also in case of clinical relevance and interpretation,
I suggest reporting the analysis of number of live birth as supplemental results.
24. Page 9, lines 21-22 and page 10 lines 1-2: This is irrelevant and can be deleted.
Discussion:
25. A better interpretation of the non-linear association of parity with the incidence of type
2 diabetes is required. What is the implication of this association? Because it is in general a
positive association and based on figure 1, the risk slightly goes down for parity>5 but the wider
CI band means that not many cases have a parity of 6 or more. Therefore, when grouped as
parity #4 and analyzed as a categorical variable, the slightly lower risk of these higher parities
is not visible in table 2. Also, the identified non-linearity (as stated in comment #17) depends
on the fit of the model and if with less knots It’s linear, then the manuscript should be changed
accordingly. Analyses of parity as a continuous and categorical variable are valuable enough as
main findings of the study.
Conclusion:
26. What do the authors mean by “the issue was more prominent among women with #3 parity/
live birth”? The manuscript can benefit from a better conclusion. Do the authors mean that
no conclusions can be drawn unless this study is replicated in other regions of Iran? This is
idealistic for any study. Therefore I suggest revising the conclusion and mentioning potential
clinical implications as well.