Review for 10.1186/s12876-025-03790-6 (2025)

Title: Frequency of Insulin Resistance among Non-Diabetic Patients with Non-Alcoholic Fatty
Liver Disease Using HOMA-IR: An Experience of a Tertiary Care Hospital in Karachi, Pakistan
Version: 3 Date: 30 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-Some sentences in the background section could be more concise to improve readability.
For example, the sentence “Considering the increase in incidence of NAFLG and IR in many
countries including Pakistan, early intervention is essential now to mitigate the progression of
NAFLD to more severe complications such as hepatocellular carcinoma (HCC) and Cirrhosis”
could be simplified for clarity.
-The phrase "Currently, the first-line treatment for NAFLD is lifestyle therapies like dietary
changes and physical activity" could be improved by specifying that these lifestyle changes are
recommended to manage and potentially reverse NAFLD.
-The mention of "lean" or "nonobese" NAFLD (NAFLD in non-obese individuals) is important
as it challenges previous assumptions about the disease's association with obesity. However,
this section could benefit from a brief explanation about why the increasing recognition of lean
NAFLD is important, especially in the context of the metabolic changes it might still cause
despite the absence of obesity.
-Some references in the background section, such as the studies by Ilkhanipoor et al. and
Gonzalez-Cantero et al., could be better integrated into the discussion. Providing a bit more
context about how these studies contribute to understanding NAFLD and IR could help tie the
background information together more smoothly.
-The reference to the Mediterranean diet could be linked more clearly to its relevance for
NAFLD. A brief explanation of how it specifically benefits NAFLD patients (e.g., through anti-
inflammatory or antioxidant effects) would help justify its mention.
-While the background mentions a gap in the literature regarding Pakistan, it could briefly
explain why this gap matters. For instance, are there unique dietary, lifestyle, or genetic factors in
Pakistan that may influence the prevalence of IR and NAFLD? Expanding on this could provide
more rationale for why local data is essential for effective healthcare interventions.
-The study mentions using a convenience sampling technique. This is practical, but it's also
important to acknowledge potential biases this method may introduce, such as selection bias. It
might be useful to mention whether any steps were taken to minimize such bias (e.g., random
selection within certain hospital settings).
-The sample size calculation is based on a 37.8% prevalence of NAFLD. While this is fine,
it would be beneficial to provide a brief explanation of how this prevalence estimate was
determined or cite the source of this data to reassure readers of its reliability.
-The formula for calculating HOMA-IR is clearly stated, but it would be helpful to specify the
exact units of measurement for fasting insulin and fasting glucose (e.g., fasting insulin in mU/L
and fasting glucose in mmol/L). While this is generally understood, confirming the units in the
materials and methods section can prevent confusion.
-While the discussion mentions differences in HOMA-IR cut-off values between regions (Iran,
Germany, Zeng et al.), the explanation could be expanded to address why these differences exist.
Is it due to genetic factors, lifestyle differences, or dietary habits? Providing some insights into
potential reasons for these regional variations would add more depth to the discussion.
-Additionally, more emphasis could be placed on why the local Pakistani population might have
different metabolic characteristics compared to these populations. Is there any evidence that
dietary patterns, urbanization, or genetic factors in Pakistan might influence the prevalence of
IR in NAFLD?
-The discussion notes that no significant differences were observed in ALT and AST levels
based on IR status in the current study, which contradicts some earlier studies. The potential
reasons for this discrepancy could be explored further. Could it be due to the methods used for
liver enzyme measurement, or could the population’s specific characteristics (e.g., degree of
liver damage, dietary factors) play a role?
-It might also be helpful to provide a bit more explanation on why GGT is often more sensitive
than AST or ALT in detecting liver dysfunction related to IR, especially in the context of this
study.