Reviewer's report
Title:Independent association of HbA1c and nonalcoholic fatty liver disease in
an elderly Chinese population
Version: 1Date:24 September 2012
Reviewer: Xin Gao
Reviewer's report:
This study provides solid evidence demonstrating an independent association
between HbAlc levels and the occurrence of non-alcoholic fatty liver disease in
an elderly community population including 1142 subjects. The finding are
interesting, and suggest a central role of liver steatosis in the pathogenesis of
glucose metabolic disorders in non-diabetic subjects. The conclusion can be
consolidated by considering the points below.
1# Materials and Methods: Page 5, Line 77. HbA1c levels reflected average
blood glucose exposure over the preceding 2-3 months, and could be affected
remarkably by several conditions in a short time, e.g. glucose-lowering treatment,
renal anemia, hemolytic anemia, et al. So subjects who have accepted
glucose-lowering treatment or had anemia should be carefully excluded from the
study in order to ensure that HbAlc stably and accurately reflect the state of
glucose metabolism.
Page 5, Line 89. Please describe the measurement of waist circumference in
detail.
2# Results: Page 8 Line 124. A great gender difference in the prevalence of
NAFLD was reported in participants younger than 50 years according to the
study by Bae JC et al. I encourage the authors to compare the prevalence of
NAFLD between male and female participants in their elderly Chinese
population.
Page 10 Line 173. How were parameters for multiple logistic regression analysis
selected? Collinearity diagnostics should be performed and multivariate analyses
modified accordingly.
3# Discussion: Paragraph 2. The most likely explanation for the association
between HbA1c and NAFLD is not discussed. Hepatic steatosis played an
important role in the pathogenesis of insulin resistance. The accumulation of
excessive fat in liver could cause severe hepatic insulin resistance and increase
the hepatic glucose production and export to the peripheral circulation, which is
also characterized by an elevation of serum HbA1c. Studies by Yki-Järvinen H et
al., D’Adamo E et al., and Bian H et al. and references within these articles shed
light on the association. Therefore, insulin resistance is the most likely
explanation for the increased HbA1c in NAFLD patients. Highlights from this
study show that even in non-diabetic participants, serum HbA1c elevation within
the normal range is closely associated with non-alcoholic fatty liver disease, so a
discussion should focus on the contribution of liver steatosis to the pathogenesis
of abnormal glucose metabolism.
4# Disscussion: Line 191. I understand the author’s rationale to explain the
association between HbA1c and NAFLD from the perspective of erythrocyte
stability and oxidative stress. Recent studies by Yu C et al. revealed the
diagnostic value of hemoglobin for non-alcoholic fatty liver disease, and the
HbA1c level could be affected by the lifespan of erythrocytes as well as serum
hemoglobin concentration. If the blood samples are available for the patients,
serum hemoglobin levels could be measured and included in the multivariate
regression analysis to adjust for the effects of serum hemoglobin on the
association between HbA1c and NAFLD. I recommend that the author should
shorten his speculation in the discussion.
Level of interest: An article whose findings are important to those with closely
related research interests
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.
Reviewer's report
Title:Independent association of HbA1c and nonalcoholic fatty liver disease in
an elderly Chinese population
Version: 1Date:24 September 2012
Reviewer: Xin Gao
Reviewer's report:
This study provides solid evidence demonstrating an independent association
between HbAlc levels and the occurrence of non-alcoholic fatty liver disease in
an elderly community population including 1142 subjects. The finding are
interesting, and suggest a central role of liver steatosis in the pathogenesis of
glucose metabolic disorders in non-diabetic subjects. The conclusion can be
consolidated by considering the points below.
1# Materials and Methods: Page 5, Line 77. HbA1c levels reflected average
blood glucose exposure over the preceding 2-3 months, and could be affected
remarkably by several conditions in a short time, e.g. glucose-lowering treatment,
renal anemia, hemolytic anemia, et al. So subjects who have accepted
glucose-lowering treatment or had anemia should be carefully excluded from the
study in order to ensure that HbAlc stably and accurately reflect the state of
glucose metabolism.
Page 5, Line 89. Please describe the measurement of waist circumference in
detail.
2# Results: Page 8 Line 124. A great gender difference in the prevalence of
NAFLD was reported in participants younger than 50 years according to the
study by Bae JC et al. I encourage the authors to compare the prevalence of
NAFLD between male and female participants in their elderly Chinese
population.
Page 10 Line 173. How were parameters for multiple logistic regression analysis
selected? Collinearity diagnostics should be performed and multivariate analyses
modified accordingly.
3# Discussion: Paragraph 2. The most likely explanation for the association
between HbA1c and NAFLD is not discussed. Hepatic steatosis played an
important role in the pathogenesis of insulin resistance. The accumulation of
excessive fat in liver could cause severe hepatic insulin resistance and increase
the hepatic glucose production and export to the peripheral circulation, which is
also characterized by an elevation of serum HbA1c. Studies by Yki-Järvinen H et
al., D’Adamo E et al., and Bian H et al. and references within these articles shed
light on the association. Therefore, insulin resistance is the most likely
explanation for the increased HbA1c in NAFLD patients. Highlights from this
study show that even in non-diabetic participants, serum HbA1c elevation within
the normal range is closely associated with non-alcoholic fatty liver disease, so a
discussion should focus on the contribution of liver steatosis to the pathogenesis
of abnormal glucose metabolism.
4# Disscussion: Line 191. I understand the author’s rationale to explain the
association between HbA1c and NAFLD from the perspective of erythrocyte
stability and oxidative stress. Recent studies by Yu C et al. revealed the
diagnostic value of hemoglobin for non-alcoholic fatty liver disease, and the
HbA1c level could be affected by the lifespan of erythrocytes as well as serum
hemoglobin concentration. If the blood samples are available for the patients,
serum hemoglobin levels could be measured and included in the multivariate
regression analysis to adjust for the effects of serum hemoglobin on the
association between HbA1c and NAFLD. I recommend that the author should
shorten his speculation in the discussion.
Level of interest: An article whose findings are important to those with closely
related research interests
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.
Please review this paper.
user
Reviewer's report
Title:Independent association of HbA1c and nonalcoholic fatty liver disease in
an elderly Chinese population
Version: 1Date:24 September 2012
Reviewer: Xin Gao
Reviewer's report:
This study provides solid evidence demonstrating an independent association
between HbAlc levels and the occurrence of non-alcoholic fatty liver disease in
an elderly community population including 1142 subjects. The finding are
interesting, and suggest a central role of liver steatosis in the pathogenesis of
glucose metabolic disorders in non-diabetic subjects. The conclusion can be
consolidated by considering the points below.
1# Materials and Methods: Page 5, Line 77. HbA1c levels reflected average
blood glucose exposure over the preceding 2-3 months, and could be affected
remarkably by several conditions in a short time, e.g. glucose-lowering treatment,
renal anemia, hemolytic anemia, et al. So subjects who have accepted
glucose-lowering treatment or had anemia should be carefully excluded from the
study in order to ensure that HbAlc stably and accurately reflect the state of
glucose metabolism.
Page 5, Line 89. Please describe the measurement of waist circumference in
detail.
2# Results: Page 8 Line 124. A great gender difference in the prevalence of
NAFLD was reported in participants younger than 50 years according to the
study by Bae JC et al. I encourage the authors to compare the prevalence of
NAFLD between male and female participants in their elderly Chinese
population.
Page 10 Line 173. How were parameters for multiple logistic regression analysis
selected? Collinearity diagnostics should be performed and multivariate analyses
modified accordingly.
3# Discussion: Paragraph 2. The most likely explanation for the association
between HbA1c and NAFLD is not discussed. Hepatic steatosis played an
important role in the pathogenesis of insulin resistance. The accumulation of
excessive fat in liver could cause severe hepatic insulin resistance and increase
the hepatic glucose production and export to the peripheral circulation, which is
also characterized by an elevation of serum HbA1c. Studies by Yki-Järvinen H et
al., D’Adamo E et al., and Bian H et al. and references within these articles shed
light on the association. Therefore, insulin resistance is the most likely
explanation for the increased HbA1c in NAFLD patients. Highlights from this
study show that even in non-diabetic participants, serum HbA1c elevation within
the normal range is closely associated with non-alcoholic fatty liver disease, so a
discussion should focus on the contribution of liver steatosis to the pathogenesis
of abnormal glucose metabolism.
4# Disscussion: Line 191. I understand the author’s rationale to explain the
association between HbA1c and NAFLD from the perspective of erythrocyte
stability and oxidative stress. Recent studies by Yu C et al. revealed the
diagnostic value of hemoglobin for non-alcoholic fatty liver disease, and the
HbA1c level could be affected by the lifespan of erythrocytes as well as serum
hemoglobin concentration. If the blood samples are available for the patients,
serum hemoglobin levels could be measured and included in the multivariate
regression analysis to adjust for the effects of serum hemoglobin on the
association between HbA1c and NAFLD. I recommend that the author should
shorten his speculation in the discussion.
Level of interest: An article whose findings are important to those with closely
related research interests
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.
assistant