Re: Sex-specific associations between cardiovascular risk factors and myocardial infarction in patients with type 2 diabetes: the ADVANCE-ON study

The manuscript reports the results from a longitudinal study examining the relative strengths of associations of several CV risk factors with MI in men and women with type 2 diabetes.

The study is well-written and report some interesting findings, especially regarding the notable differences of the effects of smoking and blood pressure on risk of MI across the two genders.

There are some points that need to be addressed, however:

Abstract:
1- Materials and methods: it is stated that the sample size is 11,065 participants from ADVANCE-ON study, while the total sample size of that study is written as 8,494 in the methods.

Introduction:
1- Page 5, line 28: delete “including diabetes”—it is mentioned in the next line.

2- Page 5, lines 46-52: the sentence “Relatively adverse atherosclerotic CVD risk factor levels in individuals with diabetes, in comparison with those without diabetes, have been found in women than in men,11-13” is not clear and needs to be rewritten.

Methods:
1- Study design and population: the actual number enrolled in the reported study is not provided.

2- Measurements of risk factors: How smoking intensity and comorbidities that were used in the adjusted models were measured?

3- Analysis: page 8, lines 49-55, it is not clear how women to men ratios are calculated from adding an interaction term to the models (are the numbers reported in Figure 2 the coefficients of the interaction terms?)

Results:
1- Again, the source study is stated as ADVANCE, while it was ADVANCE-ON in the abstract and Table 1.

2- Page 10, lines 34-49, this paragraph is confusing. Talking about subgroup analyses while the RHRs actually imply whole sample analysis. Sub-group results mean the stratum-specific results (maybe use “subgroup comparisons” instead).

Also, jumping from supplementary figures to original figures for the same group of results is confusing.

3- Do the authors mean “attributable risk” by “absolute scale”?

4- For all the figures the scale for HRs <1 is different from that of >1

Adequate review could not be completed because the authors' response to the previous review could not be accessed (only the cover letter shows). Also, the proof PDF does not show track-change.

The authors responded to some of the raised points adequately.

However, few issues remain.

1- The sample size is still not clear. Is it 11,065 from ADVANCE (Abstract), 8,498 from ADVANCE-ON (Methods and Table1), or the 5,131 who completed ADVANCE-ON? If it is the first, why mentioning all the confusing details about ADVANCE-ON? If the study is a secondary analysis of ADVANCE-ON, why including the sample size of ADVANCE in the abstract, and how come the total in Table 1 adds to 11,047 while the total sample size of ADVANCE-ON is 8,494?

What is the number of cases that actually were included in the multivariable analysis (i.e., with full information)?

2- If the smoking variable was categorized into current, former, and never, (page 7, lines 43-46), how the effect size per 10 cigarettes was calculated (page9, line 7-10)?