Review for 10.1186/1471-230X-14-34 (2014)

Reviewer's report
Title:Gender aspects suggestive of gastroparesis in patients with diabetes
mellitus: A cross-sectional survey
Version: 3Date:26 September 2013
Reviewer: Karen Bielefeldt
Reviewer's report:
MAJOR REVISIONS SUGGESTED
GENERAL COMMENT
Dickman et al. present a potentially interesting study on the prevalence of
dyspeptic symptoms in patients with NIDDM. The focus is on possible
gastroparesis and the tenor and conclusion emphasize a high prevalence and
call for screening strategies in this population. However, there are several
significant issues that raise questions about the appropriateness of this
conclusion. I have detailed my concerns below.
SPECIFIC COMMENTS:
First, there was a significant discrepancy between the description of results in the
abstract and the body of the text compared to table 1 (women seem to have
LOWER cardiovascular comorbidities, which also matches my understanding of
disease epidemiology).
Second, the authors apparently dichotomize results based on the presence or
absence of symptoms. If I look at the tables provided, symptom severity was mild
(most mean scores were below 1). Does this truly reflect dyspepsia? In my eyes,
we set the bar for dyspepsia/gastroparesis too low, which by definition inflates
prevalence data. Rey et al. recently undertook a study to assess the possible
presence of gastroparesis in the general population. Instead of dichotomizing
based on mere symptom presence as done in this manuscript, they examined
the presence of documented gastroparesis in a clinic sample and correlated
symptom scores with presence of gastroparesis. While questionable (delayed
gastric emptying poorly correlates with symptoms), they used these data to
predict the presence of gastroparesis based on weighted symptom severity
scores. Not surprisingly, the prevalence is quite a bit lower, as they dealt with a
non-clinic population and had a higher threshold for case identification. While the
data presented in this paper do not include a sample with clinical and gastric
emptying data, the authors should reconsider their approach and findings in light
of this approach.
The authors fail to address important confounders. The sample was older and
had significant comorbid conditions with multiple treatments. Calcium channel
blockers (constipation and bloating), acarbose (bloating) and exenatide (nausea)
may play a significant role in explaining the results. So, we may not deal with a
secondary consequence of diabetes, but rather the consequence of treating
disease.
I agree that the prevalence of (MILD) dyspeptic symptoms is higher than reported
for the general population. Independent of my comments about thresholds for
case definition, the authors selected a clinic population, which automatically
skews data. Looking at clinic populations, prevalence data may not differ as
much if at all (e.g., about 20% of reflux patients will meet criteria for functional
dyspepsia; dyspepsia is the primary reason for encounters in about 8% of
primary care encounters suggesting an even higher prevalence as coexisting
issue).
The discussion is too focused on gastroparesis. The authors obviously did not
examine gastroparesis, even if the GCSI was used. We may at best have data
on dyspeptic symptoms. Prior studies suggest that only a minority of these
individuals will indeed have gastroparesis. Thus, discussing the results in light of
data on gastric motility is not truly relevant in the majority of cases. This is even
more important if I assess the discussion on sex differences. While there are sex
differences in gastric emptying, perhaps mediated by sex steroids and/or NO, the
generally low prevalence of delayed emptying in symptomatic individuals makes
it highly unlikely that the sex differences are explained by sex-dependent
differences in emptying (mostly FD not GP). Similarly, the discussion on estrogen
effects (animal data) seems irrelevant. The authors themselves state the
relatively high mean age. Speculation on other confounders (HRT or obesity) are
not convincing, especially as we see female predominance with age-dependent
increases in functional dyspepsia (independent of emptying).
MINOR POINTS:
Table 2 does not give SD (indicated in the legend).