Review for 10.1186/s12876-014-0222-x (2014)

Reviewer's report
Title:Liver ENPP1 Protein Increases with Remission of Type 2 Diabetes after
Gastric Bypass Surgery
Version:2Date:5 November 2014
Reviewer: Dorit Samocha-Bonet
Reviewer's report:
This is an interesting paper reporting on liver ENPP1 gene expression and
protein in severely obese individuals with varying degrees of glucose tolerance.
ENPP1 inhibits insulin signalling and may contribute to the pathogenesis of type
2 diabetes. The authors report that unlike findings in other tissues, ENPP1 in liver
is lower in T2D and increases with resolution of T2D with gastric bypass surgery
(RYGB). Evidence is gathered from both a cross-sectional cohort and from a sub
cohort of paired cases before and after RYGB and remission of T2D. The main
strengths of the paper are the paired cases of severely obese individuals at
baseline and post-surgery with improvement in metabolic health and the access
to liver samples.
Major compulsory revisions:
1. More detail should be given on the sub-cohort that had 2 consecutive liver
biopsies. Were 14 surgeries incisional hernia repairs and 2 ring removal
procedures? Were all cases of T2D resolved? Please also see comment #4.
2. Statistical analysis: Pre / post comparisons should be tested using repeated
measure ANOVA. This will give information on differences in endpoints in
response to the intervention between the groups (NGT versus T2D).
Results:
3. What was the duration of type 2 diabetes?
4. Line 260: Of the 16 individuals, 13 pairs had liver protein extracted at both time
points. Is this the “incomplete follow up data” mentioned in line 247? Table 3
counts 8 in each group, please clarify these inconsistencies.
5. If Fig 3 is based on baseline data, why wasn't the whole cohort included
(n=55)? Did you try correlating the change in HOMA-IR or fasting insulin with the
change in the protein level in the n=13 that had pre and post samples tested?
Either HOMA-IR or fasting insulin should be presented.
Discussion:
6. Line 291: After “liver insulin sensitivity”, add: “as measured by HOMA-IR”. The
limitation of using HOMA-IR rather than the gold standard suppression of
endogenous glucose production with hyperinsulinemia should be discussed.
Especially in T2D patients where insulin secretion may be impaired. This should
be discussed in relation to the duration of T2D in this cohort.
7. Please provide differences between groups for age and BMI in Table 1.
8. Table 3: Test differences by repeated measure ANOVA.
Minor Essential Revisions
1. Abstract: need to mention the method used to measure insulin sensitivity.
2. Background: The sentence starting in line 67 is unclear to someone who is
unfamiliar with the literature on the effect of the surgery on metabolic disease.
Need to understand that the acute resolution/improvement in T2D is before
substantial weight loss is observed. Also, the use of “liver insulin resistance” in
line 67 is too strong if HOMA-IR was used. This becomes even more confusing
when in line 69 whole body insulin resistance is mentioned (how was this
measured?). Please rewrite this sentence and give sufficient detail.
3. Lines 115-118 should be moved to the Results section.
4. Lines 254-256: Choose either HOMA-IR or fasting insulin to support the
improvement in insulin sensitivity.
5. Lines 268-271: Gene expression data was not shown pre and post-surgery.
Either state "not shown" or include in the Figure (as currently stated in the Figure
legend).
6. Lines 283-289 need reference(s).
7. Line 313: check.
8. Figure legends: All Figure legends should be checked. Briefly, abbreviations
and statistical information should be listed after the legend, Fig 2 does not list A
and B and starts with C, while only having two panels. Also in Fig 2, check title
and remove statistical data from the legend. This has been given in the Results.
9. Table 1 and 2 can be combined.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I declare that I have no competing interests.