World Journal of Diabetes (World J Diabetes

World Journal of 

Diabetes 

World J Diabetes 2011 January 15; 2(1): 1-18 

P/D1 cells of fundus of the stomach Epsilon cells of the pancreas Hypothalamic arcuate nucleus 

Vagal afferent endings 

Ghrelin 

Leukocytes, Macrophages, 

T and B cells Cardiovascular system Respiratory system CNS 

↓ Immune response 

↓ TNF, IL-6, HMGB1 

↓ Inflammation and sepsis 

Akt/eNOS 

↓ Ischemia/reperfusion 

injury Atherosclerosis 

www.wjgnet.com 


↓ TNF, IL-6, HMGB1 

↓ Sepsis-induced lung injury 

ISSN 1948-9358 (online) 

GH, Corticosteroids, 

dopamine, insulin, 

leptin, etc . 

↑ Appetite 

↓ Depression 

↑Learning 

and memory

Contents 

EDITORIAL 

ORIGINAL ARTICLES 

DREAM 2020 

1 Relationship between gut and sepsis: Role of ghrelin 

Das UN 

8 Excessive 5-year weight gain predicts metabolic syndrome development in 

healthy middle-aged adults 

Lin YC, Chen JD, Chen PC 

16 Continuous positive airway pressure to improve insulin resistance and glucose 

homeostasis in sleep apnea 

Steiropoulos P, Papanas N 

WJD|www.wjgnet.com I 

Monthly Volume 2 Number 1 January 15, 2011 

January 15, 2011|Volume 2|Issue 1|

Contents 

ACKNOWLEDGMENTS 

APPENDIX 

ABOUT COVER 

AIM AND SCOPE 

FLYLEAF 

EDITORS FOR 

THIS ISSUE 

NAME OF JOURNAL 

World Journal of Diabetes 

LAUNCH DATE 

March 15, 2010 

SPONSOR 

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Volume 2 Number 1 January 15, 2011 

I Acknowledgments to reviewers of World Journal of Diabetes 

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Das UN. Relationship between gut and sepsis: Role of ghrelin 

World J Diabetes 2011; 2(1): 1-8 

http://www.wjnet.com/1948-9358/full/v2/i1/1.htm 

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wjd@wjgnet.com 

doi:10.4239/wjd.v2.i1.1 

Relationship between gut and sepsis: Role of ghrelin 

Undurti N Das 

Undurti N Das, Jawaharlal Nehru Technological University, Kakinada 

533003, India 

Undurti N Das, UND Life Sciences, Shaker Heights, OH 44120, 

United States 

Author contribution: Das UN contributed solely to this paper. 

Correspondence to: Undurti N Das, MD, FAMS, Jawaharlal 

Nehru Technological University, Kakinada 533003, 

India. Undurti@hotmail.com 

Telephone: +912162315548 Fax: +919288330316 

Received: September 19, 2010 Revised: December 22, 2010 

Accepted: December 29, 2010 

Published online: January 15, 2011 

Abstract 

Ghrelin is a growth hormone secretagogue produced 

by the gut, and is expressed in the hypothalamus 

and other tissues as well. Ghrelin not only plays an 

important role in the regulation of appetite, energy balance 

and glucose homeostasis, but also shows antibacterial 

activity, suppresses proinflammatory cytokine 

production and restores gut barrier function. In 

experimental animals, ghrelin has shown significant 

beneficial actions in preventing mortality from sepsis. 

In the critically ill, corticosteroid insufficiency as a result 

of dysfunction of the hypothalamicpituitaryadrenal 

axis is known to occur. It is therefore possible that both 

gut and hypothalamus play an important role in the 

pathogenesis of sepsis by virtue of their ability to produce 

ghrelin, which, in turn, could be a protective phenomenon 

to suppress inflammation. It remains to be 

seen whether ghrelin and its analogues are of benefit in 

treating patients with sepsis. 

© 2011 Baishideng. All rights reserved. 

Key words: Ghrelin; Sepsis; Cytokines; Inflammation; 

Critically ill; Insulin 

Peer reviewers: Vladimir N Uversky, Senior Research Professor, 

Center for Computational Biology & Bioinformatics, 

Department of Biochemistry and Molecular Biology, Indiana 

University School of Medicine, Indianapolis, IN 46202, United 

States; Joseph Fomusi Ndisang, PharmD, PhD, Assistant Pro 

WJD|www.wjgnet.com 




EDITORIAL 

fessor, College of Medicine, Epartment of Physiology, University 

of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada 

Das UN. Relationship between gut and sepsis: Role of ghrelin. 

World J Diabetes 2011; 2(1): 17 Available from: URL: http:// 

www.wjgnet.com/19489358/full/v2/i1/1.htm DOI: http://dx.doi. 

org/10.4239/wjd.v2.i1.1 

INTRODUCTION 

Ghrelin, a peptide hormone that serves as the endogenous 

ligand of the growth hormone secretagogue receptor, 

is secreted mainly by P/D1 cells lining the fundus of 

the human stomach, and the epsilon cells of the pancreas 

that stimulate hunger [1] . Ghrelin is also secreted from the 

small intestine and the colon. It is expressed in the hypothalamus, 

pituitary, and several peripheral tissues suggesting 

that it could have diverse physiological functions [25] . 

Ghrelin regulates growth hormone secretion, and plays an 

important role in the regulation of appetite, energy balance 

and glucose homeostasis. It regulates gastrointestinal, 

cardiovascular, and immune functions, and bone physiology 

[612] . Ghrelin levels increase before meals, decrease 

after meals, and serve as the counterpart of leptin, which 

induces satiation when present at higher levels. Bariatric 

procedures lead to a reduction in the amount of ghrelin 

produced, which causes the satiation that could explain 

the weight loss occurring after gastric bypass surgery. 

Receptors for ghrelin are expressed by the neurons in the 

arcuate nucleus and the ventromedial hypothalamus [13] that 

have a regulatory role in insulin secretion and participate 

in the pathophysiology of type 2 diabetes mellitus, thus 

implying that ghrelin has a role in insulin resistance. The 

ghrelin receptor is a G proteincoupled receptor. Ghrelin 

is essential for cognitive adaptation to changing environments 

and the process of learning [14] , and activates endothelial 

nitric oxide synthase (eNOS) [15,16] . Obestatin, which 

is derived from the same gene as ghrelin, has opposite ac 

tions to that of ghrelin on energy homeostasis and gastroin 

testinal function, thus adding complexity to the role of ghre 

lin in various physiological and pathological situations [17] . 

1 January 15, 2011|Volume 2|Issue 1|

positive result of intensive insulin therapy on the critically 

ill could be attributed to the prevention of sepsis, multiple 

organ failure and need for prolonged invasive organ 

support and intensive care. These results suggest that reduced 

stimulation of pituitary function seen in prolonged 

critically ill patients needs to be corrected to reverse the 

paradoxical ‘wasting syndrome’, and that maintenance of 

strict normoglycemia with insulin is important to increase 

the chances of survival of these patients. It is now believed 

that, from an endocrinological point of view, the 

acute phase and the later phase of critical illness manifest 

themselves differently. When the disease process becomes 

prolonged, there is a uniformlyreduced pulsatile secretion 

of anterior pituitary hormones, with proportionally 

reduced concentrations of peripheral anabolic hormones. 

During critical illness, prolonged activation of the HPA 

axis can result in hypercortisolemia and hypocortisolemia; 

both can be detrimental to recovery from critical illness. 

Recognition of adrenal dysfunction in critically ill patients 

is difficult because a reliable history is not available, and 

laboratory results are difficult to interpret [43,44] . For instance, 

the acute phase of critical illness is characterized 

by an actively secreting pituitary, but the concentrations of 

most peripheral effector hormones are low, partly due to 

the development of targetorgan resistance. In contrast, 

in prolonged critical illness, predominantly hypothalamic 

suppression of the (neuro)endocrine axes occurs, leading 

to the low serum levels of the respective targetorgan hormones. 

The adaptations in the acute phase are considered 

to be beneficial for shortterm survival. In the chronic 

phase, however, the observed (neuro)endocrine alterations 

contribute to the general wasting syndrome. With 

the exception of intensive insulin therapy, and perhaps 

hydrocortisone administration for a subgroup of patients, 

no hormonal intervention has proven to affect outcome 

beneficially [45] . In this context, the recently described beneficial 

actions of ghrelin in the critically ill may have important 

clinical implications. 

GHRELIN IN SEPSIS 

Experimental studies 

In the rat model of septic shock which was made by 

caecal ligation and perforation, infusion of ghrelin 10 

nmol/kg at the time of operation through the femoral 

vein, followed by a sc (subcutaneous) injection at 8 h after 

operation, revealed that, compared to that of the septic 

shock group, mean arterial blood pressure (MABP) of rats 

in the ghrelintreated group increased by 33 % (P < 0.01); 

the values of +LVdp/dtmax and LVdp/dtmax increased 

by 27 % and 33 %, respectively (P < 0.01), but LVEDP 

decreased by 33 % (P < 0.01). The plasma glucose concentration 

and myocardial ATP content increased by 

53% and 22 %, respectively, whereas plasma lactate concentration 

decreased by 40% in the ghrelintreated rats (P 

< 0.01). The plasma ghrelin level in rats with septic shock 

was 51% higher than that of rats in the sham group, 

and was negatively correlated with MABP and blood 

glucose concentration (r = 0.721 and 0.811, respectively, 

P < 0.01). The mortality rates were 47% (9/19) in rats 


Das UN. Ghrelin and sepsis 

with septic shock and 25% (3/12) in rats of the ghrelintreated 

group, respectively, suggesting that treatment with 

ghrelin could at least partially correct the abnormalities of 

hemodynamics and metabolic disturbance in septic shock 

of rats [46] . 

In an extension of these studies, it was noted that 

even endotoxininduced shock and mortality could be 

significantly decreased by ghrelin treatment in rats [47] . 

Early and late (12 h after lipopolysaccharide injection) 

treatment with ghrelin markedly increased the plasma 

glucose concentration, and decreased the plasma lactate 

concentration. This action on the part of ghrelin in increasing 

plasma glucose levels (resulting in hyperglycemia) 

may suggest that it could be harmful in the setting of 

sepsis or critical illness, since hyperglycemia is believed to 

accentuate inflammation. In the initial stages of sepsis, 

hyperglycemia (reactive hyperglycemia) as a result of 

the enhanced production of hypercortisolemia occurs, 

whereas in the later stages, hypoglycemia sets in, partly 

due to hypocortisolemia [48,49] . It was reported that during 

the early phase of sepsis, plasma glucose levels increased, 

whereas plasma insulin and glucagon levels remained 

unchanged, but corticosterone levels increased 2.5fold 

over control values. At later stages of sepsis, plasma 

glucose levels returned to normal, whereas insulin, glucagon, 

and corticosterone levels increased significantly i.e. 

40fold, 6.5fold, and 6fold respectively [48,49] . Therefore, 

the initial rise and subsequent decline in blood glucose 

correlated well with a corticosterone followed by an insulindependent 

phenomenon. Thus, blood glucose levels 

in sepsis depend to a large extent on the balance between 

corticosterone and insulin levels, and the stage of sepsis [49] . 

Hence, the ability of ghrelin to enhance plasma glucose 

levels could, especially in the later stages of sepsis, prevent 

hypoglycemia that is detrimental and ghrelin may therefore 

be useful in later stages of sepsis. Furthermore, ghrelin 

and insulin seem to have both positive and negative feedback 

control over each other [5052] , suggesting that ghrelin 

may be involved in maintaining glucose homeostasis, 

under both normal conditions and sepsis. 

Early treatment with ghrelin significantly attenuated 

the deficiency in myocardial ATP content, but late treatment 

with ghrelin had no effect on myocardial ATP content. 

The plasma ghrelin level was significantly increased 

in the rats with endotoxin shock, and it increased further 

after ghrelin administration. Exposure of rat gastric mucosa 

in vitro to lipopolysaccharide (1.0 to 100 µg/mL) triggered 

the release of ghrelin from mucosa tissue in a dose 

and timedependent manner [47] . These results suggest that 

lipopolysaccharide directly stimulates gastric mucosa to 

synthesize and secrete ghrelin, that may result in a decrease 

in endotoxininduced target organ damage. 

Ghrelin suppresses production of pro-inflammatory 

cytokines 

Ghrelin-inhibited proinflammatory cytokine production, 

mononuclear cell binding, and nuclear factorkappaB 

activation in human endothelial cells in vitro, and endotoxininduced 

cytokine production in vivo, by interacting 

with growth hormone secretagogue receptors and thus, 



P/D1 cells of fundus of the stomach Epsilon cells of the pancreas Hypothalamic arcuate nucleus 

ghrelin behaves as an endogenous anti-inflammatory mo- 

lecule [53] . These anti-inflammatory actions of ghrelin may 

explain why it is able to improve cachexia in heart fai 

lure and cancer, and to ameliorate the hemodynamic and 

metabolic disturbances in septic shock (Figure 1). By 

virtue of its anti-inflammatory action, ghrelin could play 

a modulatory role in atherosclerosis as well, especially in 

obese patients, in whom ghrelin levels are reduced. In a rat 

model of polymicrobial sepsis induced by cecal ligation 

and puncture, though ghrelin levels decreased at early (at 

5 h after ligation and puncture) or late sepsis (20 h after 

ligation and cecal puncture) its receptor was markedly 

elevated in early sepsis. Moreover, ghrelininduced relaxation 

in resistance blood vessels of the isolated small 

intestine increased significantly during early sepsis, but 

was not altered in late sepsis. GHSR1a expression in 

smooth muscle cells was significantly increased at mRNA 

and protein levels with stimulation by LPS at 10 ng/mL, 

suggesting that GHSR1a expression is upregulated, and 

vascular sensitivity to ghrelin stimulation is increased in 

the hyperdynamic phase of sepsis [54] as a compensatory 

phenomenon to septic process. Furthermore, ghrelin improved 

tissue perfusion in severe sepsis by downregulating 

endothelin1 involving a NFkappaBdependent pathway 

[55] . 

These experimental results are supported by the report 

that during postoperative intraabdominal sepsis seen in 


Vagal afferent endings 

Ghrelin 

Leukocytes, Macrophages, 

T and B cells Cardiovascular system Respiratory system CNS 


↓ TNF, IL6, HMGB1 

↓ Inflammation and sepsis 

Akt/eNOS 

↓ Ischemia/reperfusion 

injury Atherosclerosis 


↓ TNF, IL6, HMGB1 

↓ Sepsisinduced lung injury 

GH, Corticosteroids, 

dopamine, insulin, 

leptin, etc . 

↑ Appetite 

↓ Depression 

↑Learning 

and memory 

Figure 1 Scheme showing various actions of ghrelin and their possible clinical importance. Ghrelin seems to be of benefit in suppressing inflammation and 

sepsis; protects against ischemia/reperfusion-induced myocardial damage; protects lungs from sepsis-induced damage, enhances appetite, relieves depression and 

enhances learning and memory. GH: growth hormone; CNS: central nervous system. 

patients, both ghrelin and leptin plasma levels were elevated 

and positively correlated with both inflammatory cytokines 

(TNFα, IL-6) and CRP. However, this hormonal 

reaction does not seem to be specific to sepsis since a significant 

increase in both ghrelin and leptin was observed 

to occur during an uncomplicated postoperative response, 

although to a lesser extent than was shown in sepsis [56] . 

Ghrelin stimulates vagus nerve 

Ghrelin stimulates the vagus nerve. Since plasma levels of 

ghrelin were significantly reduced in sepsis; and ghrelin 

administration improved organ perfusion and function, it 

was hypothesized that ghrelin decreases pro-inflammatory 

cytokines in sepsis by means of activation of the vagus 

nerve. This is so since the vagus mediator, acetylcholine, 

has potent antiinflammatory actions and suppresses 

TNFα, IL6 and HMGB1 production by stimulating the 

alpha7 subunitcontaining nicotinic acetylcholine receptor 

(alpha7nAChR) [57,58] . As predicted, experimental studies revealed 

that vagotomy prevented ghrelin’s downregulatory 

effect on TNFα and IL-6 production, thus confirming 

that ghrelin downregulates proinflammatory cytokines 

in sepsis through activation of the vagus nerve [59] . It was 

reported that ghrelin has sympathoinhibitory properties 

that are mediated by central ghrelin receptors, involving 

a NPY/Y1 receptordependent pathway [60] . Ghrelin also 

inhibited the production of HMGB1 by activated macro 


Ghrelin 

Gut 

Disruption 

of gut 

barrier 

function 

phages, and also showed antibacterial activity [61] that may 

explain its beneficial action in sepsis and other inflammatory 

conditions [6264] . It is important to note that ghrelin 

ameliorated gut barrier dysfunction [65] , an abnormality that 

is seen in patients with sepsis. 

CONCLUSION 

Absorption 

of 

endotoxin 

CRH, ACTH, 

corticosterone 

Melanocortins 

It is evident from the preceding discussion that ghrelin 

has anti-inflammatory, para-sympathetic stimulatory and 

sympathoinhibitory effects that may underlie its beneficial 

actions in sepsis and other inflammatory conditions. 

In addition, ghrelin seems to be of significant benefit 

in improving cachexia in heart failure and cancer, and 

the ameliorization of the hemodynamic and metabolic 

disturbances in septic shock (Figure 1). The ability of 

ghrelin to suppress the synthesis and release of proinflammatory 

cytokines such as TNF-α, IL6 and HMGB1 

suggests that it may find its use in the management of 

other inflammatory conditions such as atherosclerosis, 

lupus and rheumatoid arthritis, but this remains to be 

determined. The fact that ghrelin is capable of restoring 

gut barrier function and possess antimicrobial action suggests 

that it may be useful in the management of cirrhosis 

of the liver where gut barrier function is compromised, 

leading to endotoxin absorption into the circulation. Since 

failure of gut barrier function is also one of the initial 

abnormalities seen in sepsis, ghrelin is eminently suited 

to be employed in its therapy, either by itself, or in combination 

with other therapies. These actions of ghrelin 


Infection/Injury/Surgery 

Activation of neutrophils, 

T cells and macrophages 

Elimination of invading pathogens 

Excess TNFα, IL6, MIF, 

HMGB1 

Excess free radicals, 

eicosanoids and nitric oxide 

Hypoglycemia, hypotension and 

decreased tissue perfusion 

Sepsis and septic shock 

Stimulation 

of gut 

Ghrelin 


↑ Vagal nerve 

stimulation and 

acetylcholine 

release 

Figure 2 Scheme showing the actions of ghrelin that are relevant to its potential benefit in sepsis. CRH: corticotropin-releasing hormone; ACTH: 

adrenocorticotropic hormone. 

suggest that ghrelin has the potential to be of significant 

benefit in sepsis and other critically ill patients (Figure 

2). Obviously, large scale human studies are need before 

ghrelin comes into the clinic in the management of sepsis. 

Ghrelin has been shown to have the ability to alter 

nerve cell connections and synaptic plasticity [66,67] in the 

melanocortin system, implying that ghrelin regulates me 

tabolic control by a central action. Melanocortins are kno 

wn to have anti-inflammatory actions [68,69] suggesting that 

modulation of the melanocortin system could be yet another 

means by which ghrelin could bring about its anti 

inflammatory action. It has, in fact, been reported that 

ghrelin inhibited POMC neurons [70] , and stimulated the 

hypothalamopituitaryadrenal (HPA) axis, resulting in 

the release of corticotropin-releasing hormone (CRH), 

adrenocorticotropic hormone (ACTH), and corticosterone, 

suggesting a hypothalamic site of action [71] . Thus, 

ghrelin could be producing its anti-inflammatory actions 

by inducing the release of CRH, ACTH and corticosterone. 

Ghrelin might also help prevent the stressinduced 

depression and anxiety [72,73] that is common in patients 

with sepsis and the critically ill. Ghrelin may thus be of 

significant benefit in the management of sepsis and the 

critically ill, provided that clinical trials confirm the anticipated 

benefits. 


Dr UN Das was in receipt of the Ramalingaswami Fellow- 



ship of the Department of Biotechnology, India, during 

the tenure of this study. 

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Protein Pept Lett 2010; 17: 186-196 

S- Editor Zhang HN L- Editor Herholdt A E- Editor Liu N 




doi:10.4239/wjd.v2.i1.8 

ORIGINAL ARTICLES 

Excessive 5-year weight gain predicts metabolic syndrome 

development in healthy middle-aged adults 

Yu-Cheng Lin, Jong-Dar Chen, Pau-Chung Chen 

Yu-Cheng Lin, The Department of Occupational Medicine, En 

Chu Kong Hospital, New Taipei City, 23742, Taiwan, China 

Yu-Cheng Lin, School of Medicine, Fu Jen Catholic University, 

New Taipei City 24205, Taiwan, China 

Jong-Dar Chen, Department of Family Medicine, Shin Kong 

Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan, China 

Yu-Cheng Lin, Pau-Chung Chen, Institute of Occupational Medicine 

and Industrial Hygiene, College of Public Health, National 

Taiwan University, Taipei 100, Taiwan, China 

Author contributions: Lin YC collected and analyzed data; Lin 

YC and Chen JD interpreted data; Lin YC drafted the article; 

Chen JD revised critically for important intellectual content; and 

Chen PC finally approved the version to be published. 

Correspondence to: Pau-Chung Chen, Professor, Institute of 

Occupational Medicine and Industrial Hygiene, College of Public 

Health, National Taiwan University, No. 17, Xu-Zhou Road, Taipei 

10020, Taiwan, China. pchen@ntu.edu.tw 

Telephone: +886-02-3366-8088 Fax: +886-02-2341-8570 

Received: August 31, 2010 Revised: December 1, 2010 

Accepted: December 8, 2010 

Published online: January 15, 2011 

Abstract 

AIM: To quantitatively examine the impacts of an easyto-measure 

parameter - weight gain - on metabolic 

syndrome development among middle-aged adults. 

METHODS: We conducted a five-year interval observational 

study. A total of 1384 middle-aged adults not 

meeting metabolic syndrome (MetS) criteria at the initial 

screening were included in our analysis. Baseline data 

such as MetS-components and lifestyle factors were 

collected in 2002. Body weight and MetS-components 

were measured in both 2002 and 2007. Participants 

were classified according to proximal quartiles of 

weight gain (WG) in percentages (%WG ≤ 1%, 1% < 

%WG ≤ 5%, 5% < %WG ≤ 10% and %WG > 10%, 

defined as: control, mild-WG, moderate-WG and severe- 

WG groups, respectively) at the end of the follow-up. 

Multivariate models were used to assess the association 





between MetS outcome and excessive WG in the total 

population, as well as in both genders. 

RESULTS: In total, 175 (12.6%) participants fulfilled 

MetS criteria within five years. In comparison to the control 

group, mild-WG adults had an insignificant risk for 

MetS development while adults having moderate-WG 

had a 3.0-fold increased risk for progression to MetS 

[95% confidence interval (CI), 1.8-5.1], and this risk 

was increased 5.4-fold (95% CI, 3.0-9.7) in subjects 

having severe-WG. For females having moderate- and 

severe-WG, the risk for developing MetS was 3.6 (95% 

CI, 1.03-12.4) and 5.5 (95% CI, 1.4-21.4), respectively. 

For males having moderate- and severe-WG, the odds 

ratio for MetS outcome was respectively 3.0 (95% CI, 

1.6-5.5) and 5.2 (95% CI, 2.6-10.2). 

CONCLUSION: For early-middle-aged healthy adults 

with a five-year weight gain over 5%, the severity of 

weight gain is related to the risk for developing metabolic 

syndrome. 


Key words: Excess weight gain; Metabolic syndrome; 

Middle-aged adults; Follow-up; Worker population 

Peer reviewers: Yoshinari Uehara, MD, PhD, Department of 

Cardiology, Fukuoka University Faculty of Medicine, 7-45-1 

Nanakuma, Jonan-ku, Fukuoka 814-0180 Japan; Mark A Sperling, 

MD, Professor of Pediatrics, Children's Hospital of Pittsburgh 

of UPMC, 4401 Penn Avenue, Division of Endocrinology, 

Faculty Pavilion -8th Floor, Pittsburgh, PA 15224, United States; 

Narattaphol Charoenphandhu, MD, PhD, Department of Physiology, 

Faculty of Science, Mahidol University, Rama VI Road, 

Bangkok 10400, Thailand 

Lin YC, Chen JD, Chen PC. Excessive 5-year weight gain 

predicts metabolic syndrome development in healthy middleaged 

adults. World J Diabetes 2011; 2(1): 8-15 Available from: 

URL: http://www.wjgnet.com/1948-9358/full/v2/i1/8.htm DOI: 

http://dx.doi.org/10.4239/wjd.v2.i1.8 


INTRODUCTION 

Measuring body weight is noninvasive, inexpensive and 

reliable both in terms of clinical and self-health monitoring 

[1] . Analyses from the general population have 

revealed excessive weight gain (WG) as an important risk 

factor for developing metabolic syndrome (MetS) [2,3] . MetS 

is also becoming an important concern in workplaces [4-6] 

for its impacts on both the health condition [7] and productivity 

[8] of employees. Excessive WG is common in 

the early-middle-aged population [9,10] who account for 

the majority of the workforce. However, there was a lack 

of a comprehensive follow-up survey for examining the 

possible quantitative association between WG severity 

and the risk for MetS development in the early-middleaged 

worker population. Improving our knowledge of the 

impacts of WG on MetS development is helpful to health 

promotion in workplaces. Since periodic routine health 

checkups are compulsory for employees at many worksites 

in Taiwan, we had an opportunity to conduct a workplacebased 

follow-up observation for MetS development. We 

used this approach to evaluate the impacts of excessive 

WG on MetS development among early-middle-aged employees. 

MATERIALS AND METHODS 

Participants 

A flowchart of the experimental protocol is shown below 

in the Figure 1. In 2002 and 2007, 1648 eligible employees 

of an electronic manufacturing company underwent compulsory 

health checkups in accordance with the Labor 

Health Protection Regulation of the Labor Safety and Health Act. 

The final analysis of this follow-up study only included 

subjects who did not fulfill MetS criteria in 2002. In total, 

256 employees were excluded from the study because they 

had been screened previously for MetS. Final records from 

a total of 1384 workers (338 female and 996 male workers, 

aged 18 to 58 years with a mean age of 32.3 years) made 

up the cohort for the study and for the endpoint analysis. 

Most of the employees of this electronics manufacturing 

company were residents of northern Taiwan. 

The health examination was open to all registered 

employees during every working day within a one-month 

period. All of the employees were recommended to avoid 

vigorous physical exercise for three days before their 

health examination. The subjects’ identities were anonymous 

and were not linked to the data. This analytical 

study, limited to health checkup records, followed the 

ethical criteria for human research and the study protocol 

(TYGH09702108) was reviewed and approved by the 

Ethics Committee of the Tao-Yuan General Hospital, 

Taiwan. 

Demographics, lifestyle data, and biological 

measurements 

In 2002, the examinees completed a questionnaire about 

their baseline personal history, including their lifestyle 

factors. 


Lin YC et al . Excessive weight gain predicts metabolic syndrome 

A total 1648 eligible employees completed a questionnaire about their 

baseline personal, occupational and lifestyle history; received physical 

checkups including Mets components and body weight, in 2002 

1384 workers not fulfilling Mets criteria in 2002 were 

followed up for Mets components and body weight, in 2007 

175 workers fulfilled Mets 

criteria in 2007 

Figure 1 Flowchart of experimental protocol. 

256 workers were excluded 

from the study because being 

screened Mets in 2002 

1209 workers did not fulfill 

Mets criteria in 2007 

Physical examinations and blood tests were performed 

on all participants in both 2002 and 2007. The participants 

arrived at the health care unit of the factory in the morning, 

between 07:30 and 09:30 h, after an overnight 8 

h fast. The physical examination records included measurements 

of waist circumference, weight, height and 

blood pressure. All the measuring apparatuses were rou 

tinely calibrated. Waist circumference was measured midway 

between the lowest rib and the superior border of 

the iliac crest. After being seated for 5 min, sitting blood 

pressure was measured with the dominant arm using digital 

automatic sphygmomanometers (model HEM 907, 

Omron, Japan) two times with a 5 min interval; the mean 

of these readings was used in the data analysis. After the 

physical examination, participants were placed in a reclined 

position, and venous blood (20 mL) was taken from an 

antecubital vein of the arm for subsequent tests. Blood 

specimens were centrifuged immediately thereafter, and 

were frozen and shipped on dry ice to a central clinical 

laboratory in the Tao-Yuan General Hospital (certified 

by ISO 15189 and ISO 17025). Glucose, triglyceride and 

high-density lipoprotein (HDL) cholesterol analyses were 

conducted by a Hitachi autoanalyzer model 7150 (Hitachi, 

Tokyo, Japan). 

Weight gain evaluation 

Weight gain (WG) was calculated as a percentage by the 

formula: [(body weight 2007 - body weight 2002)/body weight 

2002] and was represented as %WG. Participants were classified 

into four subgroups according to their proximal 

quartiles of increased weight gain (%WG ≤ 1%, 1% < 

%WG ≤ 5%, 5% < %WG ≤ 10% and 10% > %WG, 

defined as: control, mild-WG, moderate-WG and severe- 

WG groups, respectively) at end of the follow-up examination. 

Metabolic syndrome 

The MetS designation was made if three or more of the 

following five criteria were fulfilled: central obesity (waist 


the two genders. Also, as shown at the bottom of Table 

1, 12.6 % of total population developed MetS within five 

years; this value was 8.8% for female and was significantly 

higher for male workers, at 14.2%. 

Among the four WG subgroups (Table 2), the baseline 

measurements of body weight, body mass index, waist circumstance 

and most lifestyle factors were not significantly 

different, except that workers who had moderate and 

severe weight gain tended to snack before sleeping. The 

mean age of the severe-WG subgroup was lower than 

that of the other subgroups and the severe-WG subgroup 

was healthier than other subgroups at beginning of the 

experiment in terms of the baseline MetS-component 

measures. Table 2 also shows that the five-year occurrence 

rates of MetS were significantly higher in the moderate- 

and severe-WG subgroups. 

Since the baseline measurements were significantly 

different between the two genders, Table 3 presents the 

baseline data for the MetS-components according to the 

severity of weight gain for both genders. For the earlymiddle-aged 

females, the subjects showing severe-WG 

were younger than those in other WG groups. Although 

the majority of baseline characteristics were similar, females 

who gained a moderate or severe amount of weight 

tended to snack between meals and before sleeping (Table 

3). In our male adults, the severe WG group was the youngest 

and had better MetS-component baseline data than 

the other subgroups. Males who gained a moderate or 

severe amount of weight were inclined to snack before 

sleeping. 

Table 4 presents the changes of MetS-component 

factors and the occurrence of MetS among four WG 



Table 2 Summary of baseline characteristics of variables for the total population and five-year occurrence rates of metabolic 

syndrome according to the severity of weight gain (N = 1384) 

Baseline data WG within 5 years 

Control Mild Moderate Severe 

%WG ≤ 1% 1% < %WG ≤ 5% 5% < %WG ≤ 10% %WG > 10% 

n = 341 n =337 n =387 n =391 

Measurements; mean (standard deviation) 

Age (year) b 

33.5 (6.8) 33.3 (6.4) 32.4 (6.4) 29.7 (5.7) 

Body weight (kg) 64.4 (10.5) 63.9 (11.8) 63.6 (11.0) 62.9 (10.3) 

Body mass index (kg/m 2 ) 23.3 (2.8) 23.1 (3.0) 23.0 (3.2) 22.6 (2.9) 

Waist (cm) 76.0 (8.2) 75.8 (8.9) 75.8 (9.1) 74.5 (8.0) 

Systolic blood pressure (mmHg) a 

118.9 (14.5) 116.4 (14.4) 117.0 (15.0) 115.7 (13.3) 

Diastolic blood pressure (mmHg) b 

73.3 (9.4) 71.7 (9.3) 71.5 (9.8) 70.2 (7.8) 

Fasting blood glucose (mg/dL) a 

95.8 (15.1) 94.5 (7.9) 93.9 (7.4) 92.8 (19.5) 

Triglycerides (mg/dL) b 

115.4 (118.8) 105.5 (65.0) 98.8 (55.9) 89.9 (52.2) 

HDL cholesterol (mg/dL) 

Prevalent rates (%) 

Lifestyle factors 

49.2 (11.0) 50.6 (12.7) 50.8 (12.6) 51.6 (10.7) 

Physical exercise; > 3 times a week 34.90% 30.90% 31.30% 31.30% 

Habitual drinker 6.20% 7.10% 8.50% 3.90% 

Having snacks before sleeping (≥ third a week) b 

34.00% 35.90% 44.20% 43.30% 

Having snacks between meals (≥ third a week) 46.60% 43.60% 47.00% 48.90% 

Ever been a smoker (yes vs no) 31.10% 29.70% 33.10% 34.80% 

MetS development within 5 years 9.10% b 

9.50% b 

15.80% b 

16.00% b 

a P < 0.05; b P < 0.01; An ANOVA was conducted, adjusting for age, using a Tukey’s test. A trend test was conducted for categorical variables. WG: weight 

gain; HDL: high density lipoprotein cholesterol. 

subgroups for each gender. For our early-middle-aged 

females, the changes in the factors for central obesity 

and in Low-HDL levels were significantly less favorable 

in workers who gained moderate or severe amounts of 

weight and the development of MetS was found to be 

significantly higher in these subgroups than in others. For 

the male adults in our study, the moderate- and severs- 

WG subgroups showed significantly more unfavorable 

changes in nearly all MetS-components and had higher 

rates of MetS within five years than mild-WG and control 

subgroups. 

After controlling for the confounding factors of initial 

age, MetS-components and lifestyle factors, a multivariate 

analysis was conducted and the results are shown in Table 

5. The risk of developing MetS in subjects with moderate- 

and severe-WG was 3.0-times [95% confidence interval 

(CI), 1.8-5.1] and 5.4-times (95% CI, 3.0-9.7) greater 

than with the control group. For female workers with 

moderate- and severe-WG, the risk of developing MetS 

was 3.6-times (95% CI, 1.03-12.4) and 5.5-times (95% 

CI, 1.4-21.4) higher than the control group. Females who 

had been smokers had an increased risk (6.7 times higher, 

95% CI, 1.2-36.7) of developing MetS than those who 

had never smoked. The risk of developing MetS in male 

adults with moderate- and severe-WG was 3.0-times [95% 

confidence interval (CI), 1.6-5.5] and 5.2-times (95% CI, 

2.6-10.2) greater than the control group. 

DISCUSSION 

In this five-year interval follow up, approximately half 

of healthy middle-aged adults had a WG of over 5%, 



Table 3 Summary of baseline characteristics of variables for female and male adults according to the severity of weight gain 

and a quarter of the overall sample had a WG of more 

than 10%. Major clinical manifestations in adults, such 

as cardiovascular complications and diabetes, have been 

associated with excess WG [10,15] . In a preventive sense, our 

analyses show that the development of MetS, a precursor 

of diabetes [16,17] , is significantly quantitatively associated 

with a five-year WG exceeding 5% in healthy early-middleaged 

adults of both genders (Table 5). 

Waist circumference is an important factor for MetS. 

It is likely that weight gain contributes to increases in 

waist circumference. However, for the general population, 

the body weight measurement is less rigorous than waist 

measurement which has a specific anatomic definitions [18] 

and ,therefore, present study investigated changes in 


Female N = 388 



%WG ≤ 1% 1% < %WG ≤ 5% 5% < %WG ≤ 10% %WG >10% 

n = 105 n = 100 n = 99 n = 84 


Age (year) 33.6 (8.7) 33.0 (7.4) 33.1 (8.1) 31.1 (7.0) 

Body weight (kg) 55.3 (7.3) 53.0 (7.5) 53.5 (8.3) 55.3 (8.8) 

Body mass index (kg/m 2 ) b 

23.9 (2.7) 23.8 (2.8) 23.3 (3.0) 22.6 (2.8) 

Waist (cm) 68.8 (5.9) 67.8 (6.4) 68.1 (7.9) 69.5 (7.2) 

Systolic blood pressure (mmHg) 112.2 (13.8) 109.7 (12.1) 113.2 (14.6) 110.6 (12.9) 

Diastolic blood pressure (mmHg) 68.9 (9.0) 67.7 (8.8) 69.8 (9.6) 67.7 (8.1) 

Fasting blood glucose (mg/dL) 94.0 (9.1) 94.7 (8.6) 94.2 (7.0) 91.9 (7.4) 

Triglycerides (mg/dL) 79.4 (38.3) 73.4 (33.6) 74.0 (33.1) 73.2 (51.9) 

HDL cholesterol (mg/dL) 



53.2 (11.6) 57.1 (12.9) 56.4 (14.4) 55.6 (10.2) 

Physical exercise; ≥ 3 times a week 25.70% 26.00% 23.20% 27.40% 


Having snacks before sleeping (≥ third a week) 28.60% 26.00% 44.40% 27.40% 



Male N = 996 



%WG ≤ 1% 1% < %WG ≤ 5% 5% < %WG ≤ 10% %WG > 10% 

n = 236 n = 237 n = 288 n = 235 


Age (year) b 

33.4 (5.7) 33.5 (6.0) 32.2 (5.7) 29.2 (5.0) 

Body weight (kg) b 

68.5 (9.0) 68.6 (10.1) 67.1 (9.6) 65.6 (9.5) 

Body mass index (kg/m 2 ) 22.2 (2.8) 21.6 (2.8) 21.8 (3.5) 22.4 (3.1) 

Waist (cm) b 

79.3 (7.0) 79.2 (7.5) 78.4 (7.9) 76.3 (7.5) 

Systolic blood pressure (mmHg) b 

121.8 (13.8) 119.2 (14.3) 118.2 (14.9) 117.6 (13.0) 

Diastolic blood pressure (mmHg) b 

75.2 (8.9) 73.4 (8.9) 72.0 (9.8) 71.1 (7.6) 

Fasting blood glucose (mg/dL) 96.6 (17.1) 94.4 (7.6) 93.8 (7.5) 93.2 (22.3) 

Triglycerides (mg/dL) b 

131.5 (137.6) 119.1 (70.2) 107.3 (59.5) 95.9 (51.1) 

HDL cholesterol (mg/dL) a 



47.4 (10.3) 47.9 (11.5) 48.8 (11.3) 50.1 (10.5) 

Physical exercise; ≥ 3 times a week 39.00% 32.90% 34.00% 32.80% 


Having snacks before sleeping (≥ third a week) a 36.40% 40.10% 44.10% 48.90% 



a P < 0.05, b P < 0.01, An ANOVA was conducted, adjusting for age, using a Tukey’s test. A trend test was conducted for categorical variables; WG: weight 

gain; HDL: high density lipoprotein cholesterol. 

weight. Nevertheless, we treated waist circumference as a 

confounder in the multivariate analysis (Table 5) because 

it has a decisive influence on the development of metabolic 

syndrome. On the other hand, occupational and 

lifestyle factors naturally affect dietary behaviors and thus 

affect body weight changes [19] and other factors of atherosclerosis 

which are important in MetS development, 

including total cholesterol, low density lipoprotein cholesterol, 

uric acid and insulin. Our present study focused 

on body weight changes, and although we controlled 

some occupational, lifestyle and baseline metabolic factors 

(not shown in tables), the detailed impact of these factors 

needs to be clarified by other investigations. 

Findings from both our study (Table 4) and other 


follow-up observations [20] indicate that the adults without 

excess WG have stable or improved serum levels of 

HDL and glucose, while the adults gaining excess weight 

over several years have dramatically greater changes in 

triglyceride levels than other groups. HDL levels demonstrated 

improving trends in our middle aged sample population. 

This dissimilar to earlier findings in an elderly 

population [21] , but similar to what was shown in other 

follow-up observations for healthy Asian adults [22] . Discussing 

these findings in an earlier article [12] ; we suggested 

that our relative young healthy workers might not yet 

have reached their HDL concentration plateau so had the 

potential to increase their HDL concentration within our 



Table 4 Summary of five-year changes in metabolic syndrome-components for female and male adults and the occurrence rates of 

metabolic syndrome according to the severity of weight gain 

Female N = 388 

Follow-up changes (%) WG within 5 years 


%WG ≤ 1% 1% < %WG ≤ 5% 5% < %WG ≤ 10% %WG > 10% 

n = 105 n = 100 n = 99 n = 84 

△Central obesity b 

8.50% 16.00% 22.60% 32.80% 

△High blood pressure 22.90% 28.70% 28.50% 37.00% 

△Hyperglycemia -3.40% -4.20% -3.10% 1.30% 

△Hypertriglyceridemia b 

-0.40% 8.00% 15.60% 24.30% 

△Low-HDL cholesterol b 

-14.40% -17.70% -5.90% -6.00% 

MetS Development within 5 years b 

5.70% 3.00% 14.10% 13.10% 

Male N = 996 

Follow-up changes (%) WG within 5 years 


%WG ≤ 1% 1% < %WG ≤ 5% 5% < %WG ≤ 10% %WG > 10% 

n = 236 n = 237 n = 288 n = 235 

△Central obesity b 

10.00% 3.00% 21.20% 40.50% 

△High blood pressure a 

21.00% 20.00% 21.20% 19.00% 

△Hyperglycemia -8.00% -11.00% -5.10% -2.40% 

△Hypertriglyceridemia b 

2.00% 2.00% 8.10% 11.90% 

△Low-HDL cholesterol b 

-34.00% -24.00% -24.20% -7.10% 

MetS development within 5 years 10.60% 12.20% 16.30% 17.00% 

a b 

P < 0.05; P < 0.01; An ANOVA was conducted, adjusting for age, using Tukey’s test. Δ: Differences between 2007 and 2002; minus indicates decreasing 

trend within follow-up; WG: weight gain; HDL: high density lipoprotein cholesterol. 

Table 5 The adjusted risks for development of metabolic 

syndrome 

WG severities Odd ratio 95% CI 

Total population 

Mild WG (1% < %WG < 5%) 1.2 0.70 - 2.2 

Moderate WG (5% < %WG < 10%) b 

3.0 1.80 - 5.1 

Severe WG (%WG > 10%) b 

Female 

5.4 3.00 - 9.7 

Mild WG (1% < %WG < 5%) 0.9 0.20 - 4.5 

Moderate WG (5% < %WG < 10%) a 

3.6 1.03 - 12.4 


Male 

5.5 1.40 - 21.4 

Mild WG (1% < %WG < 5%) 1.4 0.70 - 2.7 

Moderate WG (5% < %WG < 10%) b 

3/0 1.60 - 5.5 


5.2 2.60 - 10.2 

a b 

P < 0.05; P < 0.01; Adjusted variables were age, metabolic syndrome 

components and lifestyle and occupational factors; WG: weight gain. 

follow-up. Significantly, moderate or severe weight gainers 

had much lower capacity for increasing their HDL levels 

than those free from significant weight gain (Table 4). 

In addition, as presented in Tables 3 and 4, although the 

severe-WG subgroups were the youngest (mean aged 31 

years) at the outset, after five years they showed the worst 

changes in all MetS-components and the highest MetS 

occurrence rate among the workers examined. We found 

that the glucose and lipid metabolism capabilities in our 

young workers with excessive WG became significantly 

worse than in older subjects without excessive WG. This 

phenomenon supports, in terms of nutritional metabolism, 

the hypothesis that rapidly becoming obese can 

speed up the aging process in adults [23] . Experts have sug- 

gested that public health efforts need to tackle rapid WG 

in adolescents [24] and our findings indicate that these efforts 

should be extended to early-middle-aged workers. 

Since “yo-yo” effects [25] have appeared in many trials for 

weight reduction, body weight monitoring and preventing 

excess WG is an important strategy for maintaining heal- 

thy lipid and sugar metabolism in early-middle-aged workers. 

Weight gain of more than 5% within a five-year 

period should be avoided in order to prevent the development 

of MetS. On the other hand, limited weight gain was 

previously found not to be a risk factor for diabetes [15] and 

in the present analysis, five-year mild-WG (< 5% WG) 

appeared to be tolerable in terms of progression to MetS 

(Table 5). 

For both genders, there were differences in dietary 

habits among our four WG subgroups: the moderate- and 

severe- weight gainers were significantly more likely to 

snack between meals or before sleep (Table 3). The major 



weight-related behaviors in late-adolescence are snack- 

ing and late-night eating [26] .Further more, a study on twins 

showed that night-time eating was significantly more com- 

mon in obese subjects than in subjects with normal weight 

[27] . Because awareness of weight control is itself bene- 

ficial for the prevention of MetS [28] and our workers who 

gained excessive weight tended to snack in addition to 

regular meals, education and reminders of healthy dietary 

behaviors for employees are essential for MetS mana- 

gement in workplaces. Dietary behavior is an important 

but complex issue in surveys concerning MetS development 

[29,30] . However, there is a lack of precise data regarding 

caloric intake and dietary contents in the current 

analysis, and this might explain why our multivariate analysis 

involving dietary behaviors did not reach a statistical 

significance for MetS outcome. Future surveys for MetS 

in workplaces should focus on the details of dietary behaviors 

among employees. 

The present observational approach demonstrated a 

significant association between severity of weight gain 

and MetS outcome. However, there are several research 

limitations should be addressed. Because National Health 

Insurance in Taiwan provides convenient medical care 

for subjects with MetS traits, it was difficult to avoid 

confounding protective effects from the correction efforts 

for MetS components [31] during the period of our follow 

up. At the same time, our conclusions were drawn from 

the relatively healthy employees by excluding the data of 

the workers who fulfilled the MetS criteria at baseline 

and, thus “healthy-worker effects [32] ” might be involved. 

Given the conditions mentioned above, it is possible 

that we might have underestimated the risk for MetS outcome. 

Finally, our findings were obtained from a five- year 

interval approach and thus the possible impacts on MetS 

outcomes of body weight changes over a shorter time 

period require further study. In conclusion, for early-middle-aged 

healthy adults with a five-year weight gain over 

5%, severity of weight gain is quantitatively associated 

with the risk for metabolic syndrome development. We 

suggest prioritizing the optimization of body weight and 

modifications in dietary behaviors for the prevention of 

metabolic syndrome among early-middle-aged workers. 


The authors would like to thank the personnel of the 

Department of Family Medicine, Center of Health Management 

in the Tao-Yuan General Hospital for their support 

and generous assistance. 

COMMENTS 

Background 

Measuring body weight is noninvasive, inexpensive and reliable both in terms 

of clinical and self-health monitoring. Analyses from the general population 

have revealed excessive weight gain (WG) as an important risk factor for 

developing metabolic syndrome (MetS), which is becoming an important 

concern in workplaces for its impacts on both health conditions and productivity 

of employees. Excessive WG is common in the early-middle-aged population 


who account for the majority of the workforce. However, there was a lack of 

a comprehensive follow-up survey for examining the quantitative association 

between WG severity and the risk for MetS development in the early-middle-aged 

worker population. 

Research frontiers 

Improving our knowledge of the impacts of WG on MetS development is helpful to 

health promotion in workplaces. Periodic routine health checkups are compulsorily 

for employees at many worksites in Taiwan, thus we had an opportunity to 

conduct a workplace-based follow-up observation of MetS development. We used 

this approach to evaluate the impacts of excessive WG on MetS development 

among early-middle-aged employees. 

Innovations and breakthroughs 

In comparison to the control group, mild-WG adults had an insignificant risk for 

MetS development, while adults having moderate-WG had a 3.0-fold increased 

risk for progression to MetS [95% confidence interval (CI), 1.8-5.1], and this risk 

was increased 5.4-fold (95% CI, 3.0-9.7) in subjects having severe-WG. For 

females having moderate- and severe-WG, the risk for developing MetS was 3.6 

(95% CI, 1.03-12.4) and 5.5 (95% CI, 1.4-21.4), respectively. For males having 

moderate- and severe-WG, the odds ratio for MetS outcome was respectively 3.0 

(95% CI, 1.6-5.5) and 5.2 (95% CI, 2.6-10.2). 

Applications 

For early-middle-aged healthy adults with a five-year weight gain over 5%, severity 

of weight gain is related to the risk for developing metabolic syndrome. We 

suggest prioritizing body weight optimization and modifications in dietary behaviors 

for the prevention of metabolic syndrome among early-middle-aged workers. 

Terminology 

A designation of Metabolic Syndrome was made if three or more of the following 

five criteria were fulfilled: central obesity (waist circumference > 90 cm for males 

and > 80 cm for females based on Taiwanese criteria); High blood pressure 

(systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85 mmHg); 

hyperglycemia (fasting sugar ≥ 100 mg/dL); hypertriglyceridemia (triglycerides 

≥ 150 mg/dL); and low-HDL-cholesterolemia (high density lipoprotein cholesterol 

(HDL) < 40 mg/dL for males, < 50 for females). 

Peer reviews 

The major finding of the study is that weight gain, especially in the higher centiles 

is more likely to be associated with the development of the metabolic syndrome. 

Overall, this is a timely paper that could lead to public health measures 

encouraging exercise and care in the calorie consumption of workers in large 

plants. The benefits to the involved individuals, the companies they work for and 

society at large could be significant. 

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S- Editor Zhang HN L- Editor Hughes D E- Editor Liu N 


ness and quality of life [5,6] . CPAP is commonly used to 

treat OSAS by delivering a constant pressure throughout 

inspiration and expiration to maintain upper airway patency 

during sleep. It consists of a flow generator that delivers 

airflow at a constant pressure to the patient through a 

mask via a tubing system. CPAP technology has improved 

considerably over the years. This technological progress 

notwithstanding, patient adherence to CPAP treatment 

remains suboptimal and its use during sleep time shows 

substantial variation between patients [7] . 

CONTINUOUS POSITIVE AIRWAY 

PRESSURE: ITS ROLE IN GLUCOSE 

HOMEOSTASIS 

Not only is CPAP the established treatment for OSAS, 

it may also have a favorable effect on insulin resistance 

and glucose metabolism in such patients. It has been postulated 

that CPAP can ameliorate intermittent hypoxia 

and sympathetic overactivation, both pathophysiological 

mechanisms responsible for the impaired glucose metabolism 

in OSAS patients. This additional therapeutic benefit 

conferred by CPAP is now attracting considerable interest 

but is still an issue of ongoing debate [8] . Indeed, findings 

from numerous studies on the effect of CPAP treatment 

on glucose metabolism, both in diabetic and non-diabetic 

populations, have been rather conflicting. This can be 

attributed to differences between the studied populations 

(i.e. diabetic, non-diabetic, obese or non-obese patients), 

the primary outcomes, the method of assessment of glucose 

metabolism (i.e. fasting glucose, glycated hemoglobin, 

hyperinsulinemic euglycemic clamp etc.), the period 

of CPAP application (ranging between 1 night and 2.9 

years) [8] and the patient’s adherence to CPAP use [9] . Unfortunately, 

only three randomised control studies have so 

far examined the effect of CPAP on different parameters 

of glucose metabolism [10-12] and only one, the most recent, 

has shown a favorable effect. 

The latter [10] demonstrated an increase in insulin sen- 

sitivity among the 31 patients with moderate/severe OS 

AS who received CPAP treatment, as opposed to no improvement 

among the 30 controls receiving sham CPAP. 

An additional improvement was also recorded after 12 

wk of CPAP use in subjects with body mass index exceeding 

25 kg/m 2[10] . The authors have used the short 


Steiropoulos P et al . CPAP in sleep apnea 

Table 1 Summary of the 3 randomised controlled trials which examined the role of continuous positive airway pressure on glucose 

homeostasis 

Author Patients Duration Methods Results 

Lam et al [10] 

West et al [11] 

Coughlin et al [12] 

61 1 wk Short insulin tolerance test Increase in insulin sensitivity after 1 wk of CPAP use. Further improvement 

after 12 wk in subjects with BMI < 25 kg/m 2 

12 wk 

42 3 mo Hyperinsulinemic euglycemic clamp, 

HOMA index, HbA1C 

No difference after 3 mo of APAP use 

24 6 wk Fasting glucose, insulin, HOMA index No difference 

CPAP: continuous positive airway pressure; APAP: automatic positive airway pressure; BMI: body mass index; HbA1c: haemoglobin A1c. 

insulin tolerance test, a rapid and simple test that has 

been validated against clamp studies [13] and whose short 

duration inhibits interference from counter regulatory 

hormones [14] . Additional strengths of the study include 

good CPAP adherence and exclusion of OSA patients 

with comorbidities, a fact that allows a clear delineation of 

the impact of OSA per se on glucose metabolism. 

Conversely, two further randomised control studies 

indicate that CPAP treatment does not improve glucose 

metabolism. The first one by West et al [11] compared 20 

OSAS patients receiving automatic positive airway pressure 

(APAP) therapy with 22 OSAS patients receiving 

sham therapy for 3 mo (Table 1). All patients were male 

with established type 2 diabetes mellitus. There was no sig- 

nificant change in haemoglobin A1C (HbA1c), insulin sen- 

sitivity assessed by euglycemic clamp and HOMA in 

either group [11] . Even after excluding 8 patients with poor 

compliance, changes remained insignificant [11] . The other 

study by Coughlin et al [12] was a randomised placebocontrolled 

blinded cross-over trial, comparing 6 wk of 

therapeutic and sham CPAP in 34 obese OSAS patients. 

No change occurred in fasting glucose and insulin levels 

or insulin resistance, as assessed by HOMA [12] . Nonetheless, 

it should be borne in mind that the study period 

was rather short. Indeed, the authors themselves queried 

whether a prolonged longer study period would be necessary 

to reveal significant changes [12] . 

Clearly, the role of CPAP in the improvement of glu- 

cose metabolism and insulin sensitivity has not been defined 

yet [8] . Results are conflicting which may be explained 

by the differences in recruited populations (diabetic or 

non-diabetic), adherence to CPAP use, as well as in study 

design (duration of follow-up) and endpoints (different 

parameters of insulin resistance and glucose homeostasis) 

[8] . In addition, other issues such as the role of diet and 

exercise should always be addressed. 

CONCLUSIONS AND FUTURE 

DIRECTIONS 

In the light of current knowledge, further research therefore 

needs to revisit the effect of CPAP on glucose homeostasis 

[8] . It is important to define which patients stand 

to benefit and how long the treatment takes to produce 

favorable changes. Moreover, the magnitude of the effect 

needs to be re-evaluated in terms of quantifying the 


Steiropoulos P et al . CPAP in sleep apnea 

changes in insulin sensitivity, fasting and post-prandial glucose 

levels and HbA1c. These issues should be addressed 

by large-scale, long-term, randomised controlled trials. 

In the authors’ opinion, the accumulating evidence for a 

positive effect of CPAP on glycemic control is very promising 

and warrants careful attention. It has recently been 

realised that OSAS aggravates glycemic control, even at 

the earliest stages of glucose intolerance [15] , opening rich 

perspectives for application of CPAP. Patient health care 

is anticipated to have improved by 2020 and physicians 

will be able to make better and more individualised use of 

CPAP to affect favorable changes in glucose homeostasis, 

targeting both hypoxia and hyperglycemia. 

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S- Editor Zhang HN L- Editor Roemmele A E- Editor Liu N 






Acknowledgments to reviewers of World Journal of 


Many reviewers have contributed their expertise and 

time to the peer review, a critical process to ensure the 

quality of World Journal of Diabetes. The editors and 

authors of the articles submitted to the journal are 

grateful to the following reviewers for evaluating the 

articles (including those published in this issue and those 

rejected for this issue) during the last editing time period. 

Marcin Baranowski, PhD, Department of Physiology, Medical 

University of Bialystok, Mickiewicza 2c, Bialystok 15-222, Poland 

Narattaphol Charoenphandhu, MD, PhD, Department of Physiology, 

Faculty of Science, Mahidol University, Rama VI Road, 

Bangkok 10400, Thailand 

Nigel Irwin, PhD, School of Biomedical Sciences, University of 

Ulster, Coleraine, Northern Ireland, BT52 1SA, United Kingdom 

Arulmozhi D Kandasamy, PhD, Cardiovascular Research Centre, 

4-62 Heritage Medical Research Centre, University of Alberta, Edmonton 

T6G 2S2, Alberta, Canada 

Reema Mody, PhD, MBA, Principal Scientist, Global Health 

Economic and Outcomes Research, Takeda Pharmaceuticals International, 

Inc., 33976 Wooded Glen Dr. Grayslake, IL 60030, United 

States 

Joseph Fomusi Ndisang, PharmD, PhD, Assistant Professor, 

College of Medicine, Epartment of Physiology, University of Saskatchewan, 

107 Wiggins Road, Saskatoon, SK, Canada 


World J Diabetes 2011 January 15; 2(1): I 



Craig S Nunemaker, PhD, University of Virginia, Charlottesville, 

VA 22901, United States 

Luciano Pirola, PhD, Epigenetics in Human Health and Disease 

Laboratory, Baker IDI Heart and Diabetes Institute, 75 Commercial 

Road, Melbourne, VIC 3004, Australia 

Cristina Rabadán-Diehl, PhD, MPH, Program Director, Division 

of Cardiovascular Diseases, National Heart, Lung, and Blood 

Institute/NIH, Rockledge II, Suite 8156, 6701 Rockledge Drive, 

Bethesda, MD 20892-7956, United States 

Mark A Sperling, MD, Professor of Pediatrics, Children's Hospital 

of Pittsburgh of UPMC, 4401 Penn Avenue, Division of Endocrinology, 

Faculty Pavilion -8th Floor, Pittsburgh, PA 15224, United 

States 

Greg Tesch, PhD, Department of Nephrology, Monash Medical 

Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia 

Yoshinari Uehara, MD, PhD, Department of Cardiology, Fukuoka 

University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, 

Fukuoka 814-0180 Japan 

Vladimir N Uversky, Senior Research Professor, Center for 

Computational Biology & Bioinformatics, Department of Biochemistry 

and Molecular Biology, Indiana University School of Medicine, 

Indianapolis, IN 46202, United States 

Kevin CJ Yuen, MBChB, MRCP, CCST, MD, Department of 

Endocrinology, Oregon Health and Science University, 3181 SW 

Sam Jackson Park Road, Mailcode L607, Portland, OR 97239, 

United States 





Meetings 

Events Calendar 2011 

January 14-15, 2011 

AGA Clinical Congress of 

Gastroenterology and Hepatology: 

Best Practices in 2011 Miami 

FL, United States 

January 28, 2011 

Diabetes UK and External 

Conferences 

Diabetes Awareness Training 

London, United Kingdom 

January 28-29, 2011 

9. Gastro Forum München 

Munich, Germany 

February 13-27, 2011 

Gastroenterology: New Zealand 

CME Cruise Conference 

Sydney, NSW, Australia 

February 16-19, 2011 

The 4th International Conference on 

Advance Technologies & Treatments 

for Diabetes 

London, United Kingdom 

February 24-26, 2011 

2nd International Congress on 

Abdominal Obesity 

Buenos Aires, Brazil 

February 26-March 1, 2011 

Canadian Digestive Diseases Week, 

Westin Bayshore, Vancouver 

British Columbia, Canada 

February 28-March 1, 2011 

Childhood & Adolescent Obesity: A 

Whole-system Strategic Approach 

Abu Dhabi, United Arab Emirates 

March 3-5, 2011 

42nd Annual Topics in Internal 

Medicine 

Gainesville, FL, United States 

March 14-17, 2011 

British Society of Gastroenterology 

Annual Meeting 2011, Birmingham 

England, United Kingdom 

March 17-20, 2011 

Mayo Clinic Gastroenterology & 

Hepatology 

Jacksonville, FL , United States 

March 18, 2011 

UC Davis Health Informatics: 

Change Management and Health 

Informatics, The Keys to Health 

Reform 

Sacramento, CA, United States 

March 25-27, 2011 

MedicReS IC 2011 Good Medical 

Research 

Istanbul, Turkey 

March 28–30, 2011 

The Second World Congress on 

Interventional Therapies for Type 2 


New York, United States 

April 25-27, 2011 

The Second International Conference 

of the Saudi Society of Pediatric 

Gastroenterology, Hepatology & 

Nutrition 

Riyadh, Saudi Arabia 

May 7-10, 2011 

Digestive Disease Week 

Chicago, IL, United States 


June 2-5, 2011 

The 1st Asia Pacific Congress on 

Controversies to Consensus in 

Diabetes, Obesity and Hypertension 

Shanghai, China 

June 11-12, 2011 

The International Digestive Disease 

Forum 2011 

Hong Kong, China 

June 22-25, 2011 

ESMO Conference: 13th World 

Congress on Gastrointestinal Cancer 

Barcelona, Spain 

August 3-6, 2011 

AADE 38th Annual Meeting 

Las Vegas, United States 

October 16-18, 2011 

ISPAD Science School for Health 

Professionals 

Miami, Unites States 

October 19-22, 2011 

ISPAD 36th Annual Meeting 

Miami, United States 

October 22-26, 2011 

19th United European 

Gastroenterology Week 

Stockholm, Sweden 

October 26-29, 2011 

CDA/CSEM Professional 

Conference and Annual Meetings 

Toronto, Ontario, Canada 

October 28-November 2, 2011 

ACG Annual Scientific Meeting & 

Postgraduate Course 

Washington, DC, United States 

November 10-12, 2011 

The Second International Diabetes & 

Obesity Forum 

Istanbul, Turkey 

World J Diabetes 2011 January 15; 2(1): I 







Instructions to authors 

GENERAL INFORMATION 

World Journal of Diabetes (World J Diabetes, WJD, online ISSN 

1948-9358, DOI: 10.4239), is a monthly, open-access (OA), pe 

er-reviewed journal supported by an editorial board of 323 experts 

in diabetes mellitus research from 38 countries. 

The biggest advantage of the OA model is that it provides 

free, full-text articles in PDF and other formats for experts and 

the public without registration, which eliminates the obstacle that 

traditional journals possess and usually delays the speed of the 

propagation and communication of scientific research results. 

Maximization of personal benefits 

The role of academic journals is to exhibit the scientific levels of 

a country, a university, a center, a department, and even a scientist, 

and build an important bridge for communication between 

scientists and the public. As we all know, the significance of the 

publication of scientific articles lies not only in disseminating 

and communicating innovative scientific achievements and academic 

views, as well as promoting the application of scientific 

achievements, but also in formally recognizing the “priority” and 

“copyright” of innovative achievements published, as well as 

evaluating research performance and academic levels. So, to realize 

these desired attributes of WJD and create a well-recognized 

journal, the following four types of personal benefits should be 

maximized. The maximization of personal benefits refers to the 

pursuit of the maximum personal benefits in a well-considered 

optimal manner without violation of the laws, ethical rules and the 

benefits of others. (1) Maximization of the benefits of editorial 

board members: The primary task of editorial board members 

is to give a peer review of an unpublished scientific article via 

online office system to evaluate its innovativeness, scientific and 

practical values and determine whether it should be published or 

not. During peer review, editorial board members can also obtain 

cutting-edge information in that field at first hand. As leaders in 

their field, they have priority to be invited to write articles and 

publish commentary articles. We will put peer reviewers’ names 

and affiliations along with the article they reviewed in the journal to 

acknowledge their contribution; (2) Maximization of the benefits 

of authors: Since WJD is an open-access journal, readers around 

the world can immediately download and read, free of charge, highquality, 

peer-reviewed articles from WJD official website, thereby 

realizing the goals and significance of the communication between 

authors and peers as well as public reading; (3) Maximization of 

the benefits of readers: Readers can read or use, free of charge, 

high-quality peer-reviewed articles without any limits, and cite 

the arguments, viewpoints, concepts, theories, methods, results, 

conclusion or facts and data of pertinent literature so as to validate 

the innovativeness, scientific and practical values of their own 

research achievements, thus ensuring that their articles have novel 

arguments or viewpoints, solid evidence and correct conclusion; 

and (4) Maximization of the benefits of employees: It is an 

iron law that a first-class journal is unable to exist without firstclass 

editors, and only first-class editors can create a first-class 

academic journal. We insist on strengthening our team cultivation 

and construction so that every employee, in an open, fair and 

transparent environment, could contribute their wisdom to edit 

and publish high-quality articles, thereby realizing the maximization 

of the personal benefits of editorial board members, authors and 

readers, and yielding the greatest social and economic benefits. 


I 

World J Diabetes 2011 January 15; 2(1): I-V 



Aims and scope 

The major task of WJD is to report rapidly the most recent results 

in basic and clinical research on diabetes including: metabolic syndrome, 

functions of α, β, δ and PP cells of the pancreatic islets, 

effect of insulin and insulin resistance, pancreatic islet transplantation, 

adipose cells and obesity, clinical trials, clinical diagnosis and 

treatment, rehabilitation, nursing and prevention. This covers epidemiology, 

etiology, immunology, pathology, genetics, genomics, 

proteomics, pharmacology, pharmacokinetics, pharmacogenetics, 

diagnosis and therapeutics. Reports on new techniques for treating 

diabetes are also welcome. 

Columns 

The columns in the issues of WJD will include: (1) Editorial: To 

introduce and comment on major advances and developments 

in the field; (2) Frontier: To review representative achievements, 

comment on the state of current research, and propose directions 

for future research; (3) Topic Highlight: This column consists of 

three formats, including (A) 10 invited review articles on a hot 

topic, (B) a commentary on common issues of this hot topic, and 

(C) a commentary on the 10 individual articles; (4) Observation: 

To update the development of old and new questions, highlight 

unsolved problems, and provide strategies on how to solve the 

questions; (5) Guidelines for Basic Research: To provide guidelines 

for basic research; (6) Guidelines for Clinical Practice: To provide 

guidelines for clinical diagnosis and treatment; (7) Review: To 

review systemically progress and unresolved problems in the field, 

comment on the state of current research, and make suggestions 

for future work; (8) Original Article: To report innovative and 

original findings in diabetes; (9) Brief Article: To briefly report 

the novel and innovative findings in diabetes research; (10) Case 

Report: To report a rare or typical case; (11) Letters to the Editor: 

To discuss and make reply to the contributions published in WJD, 

or to introduce and comment on a controversial issue of general 

interest; (12) Book Reviews: To introduce and comment on quality 

monographs of diabetes mellitus; and (13) Guidelines: To introduce 

consensuses and guidelines reached by international and national 

academic authorities worldwide on basic research and clinical 

practice in diabetes mellitus. 

Name of journal 


CSSN 


Indexing/abstracting 

PubMed Central,PubMed 

Published by 

Baishideng Publishing Group Co., Limited 

SPECIAL STATEMENT 

All articles published in this journal represent the viewpoints of the 

authors except where indicated otherwise. 

Biostatistical editing 

Statisital review is performed after peer review. We invite an expert 

in Biomedical Statistics from to evaluate the statistical method used 

in the paper, including t-test (group or paired comparisons), chisquared 

test, Ridit, probit, logit, regression (linear, curvilinear, or 



stepwise), correlation, analysis of variance, analysis of covariance, 

etc. The reviewing points include: (1) Statistical methods should be 

described when they are used to verify the results; (2) Whether the 

statistical techniques are suitable or correct; (3) Only homogeneous 

data can be averaged. Standard deviations are preferred to standard 

errors. Give the number of observations and subjects (n). Losses 

in observations, such as drop-outs from the study should be reported; 

(4) Values such as ED50, LD50, IC50 should have their 

95% confidence limits calculated and compared by weighted probit 

analysis (Bliss and Finney); and (5) The word ‘significantly’ should 

be replaced by its synonyms (if it indicates extent) or the P value (if 

it indicates statistical significance). 

Conflict-of-interest statement 

In the interests of transparency and to help reviewersassess any 

potential bias, WJD requires authors of all papers to declare any 

competing commercial, personal, political, intellectual, or religious 

interests in relation to the submitted work. Referees are also asked 

to indicate any potential conflict they might have reviewing a 

particular paper. Before submitting, authors are suggested to read 

“Uniform Requirements for Manuscripts Submitted to Biomedical 

Journals: Ethical Considerations in the Conduct and Reporting of 

Research: Conflicts of Interest” from International Committee of 

Medical Journal Editors (ICMJE), which is available at: http://www. 

icmje.org/ethical_4conflicts.html. 

Sample wording: [Name of individual] has received fees for 

serving as a speaker, a consultant and an advisory board member for 

[names of organizations], and has received research funding from 

[names of organization]. [Name of individual] is an employee of 

[name of organization]. [Name of individual] owns stocks and shares 

in [name of organization]. [Name of individual] owns patent [patent 

identification and brief description]. 

Statement of informed consent 

Manuscripts should contain a statement to the effect that all human 

studies have been reviewed by the appropriate ethics committee 

or it should be stated clearly in the text that all persons gave their 

informed consent prior to their inclusion in the study. Details that 

might disclose the identity of the subjects under study should be 

omitted. Authors should also draw attention to the Code of Ethics 

of the World Medical Association (Declaration of Helsinki, 1964, 

as revised in 2004). 

Statement of human and animal rights 

When reporting the results from experiments, authors should 

follow the highest standards and the trial should comform to Good 

Clinical Practice (for example, US Food and Drug Administration 

Good Clinical Practice in FDA-Regulated Clinical Trials; UK 

Medicines Research Council Guidelines for Good Clinical Practice 

in Clinical Trials) and/or the World Medical Association Declaration 

of Helsinki. Generally, we suggest authors follow the lead investigator’s 

national standard. If doubt exists whether the research 

was conducted in accordance with the above standards, the authors 

must explain the rationale for their approach and demonstrate 

that the institutional review body explicitly approved the doubtful 

aspects of the study. 

Before submitting, authors should make their study approved 

by the relevant research ethics committee or institutional review 

board. If human participants were involved, manuscripts must be 

accompanied by a statement that the experiments were undertaken 

with the understanding and appropriate informed consent of each. 

Any personal item or information will not be published without 

explicit consents from the involved patients. If experimental animals 

were used, the materials and methods (experimental procedures) 

section must clearly indicate that appropriate measures were taken to 

minimize pain or discomfort, and details of animal care should be 

provided. 

SUBMISSION OF MANUSCRIPTS 

Manuscripts should be typed in 1.5 line spacing and 12 pt. Book 

WJD|www.wjgnet.com II 

Antiqua with ample margins. Number all pages consecutively, and 

start each of the following sections on a new page: Title Page, Abstract, 

Introduction, Materials and Methods, Results, Discussion, 

Acknowledgements, References, Tables, Figures, and Figure Legends. 

Neither the editors nor the publisher are responsible for the 

opinions expressed by contributors. Manuscripts formally accepted 

for publication become the permanent property of Baishideng 

Publishing Group Co., Limited, and may not be reproduced by any 

means, in whole or in part, without the written permission of both 

the authors and the publisher. We reserve the right to copy-edit and 

put onto our website accepted manuscripts. Authors should follow 

the relevant guidelines for the care and use of laboratory animals 

of their institution or national animal welfare committee. For the 

sake of transparency in regard to the performance and reporting 

of clinical trials, we endorse the policy of the International Committee 

of Medical Journal Editors to refuse to publish papers 

on clinical trial results if the trial was not recorded in a publiclyaccessible 

registry at its outset. The only register now available, 

to our knowledge, is http://www. clinicaltrials.gov sponsored by 

the United States National Library of Medicine and we encourage 

all potential contributors to register with it. However, in the case 

that other registers become available you will be duly notified. A 

letter of recommendation from each author’s organization should 

be provided with the contributed article to ensure the privacy and 

secrecy of research is protected. 

Authors should retain one copy of the text, tables, photographs 

and illustrations because rejected manuscripts will not be returned 

to the author(s) and the editors will not be responsible for loss or 

damage to photographs and illustrations sustained during mailing. 

Online submissions 

Manuscripts should be submitted through the Online Submission 

System at: http://www.wjgnet.com/1948-9358office. Authors are 

highly recommended to consult the ONLINE INSTRUCTIONS 

TO AUTHORS (http://www.wjgnet.com/1948-9358/ 

g_info_20100107165233.htm) before attempting to submit online. 

For assistance, authors encountering problems with the Online 

Submission System may send an email describing the problem 

to wjd@wjgnet.com, or by telephone: +86-10-59080038. If you 

submit your manuscript online, do not make a postal contribution. 

Repeated online submission for the same manuscript is strictly 

prohibited. 

MANUSCRIPT PREPARATION 

All contributions should be written in English. All articles must be 

submitted using word-processing software. All submissions must 

be typed in 1.5 line spacing and 12 pt. Book Antiqua with ample 

margins. Style should conform to our house format. Required 

information for each of the manuscript sections is as follows: 

Title page 

Title: Title should be less than 12 words. 

Running title: A short running title of less than 6 words should 

be provided. 

Authorship: Authorship credit should be in accordance with the 

standard proposed by International Committee of Medical Journal 

Editors, based on (1) substantial contributions to conception and 

design, acquisition of data, or analysis and interpretation of data; (2) 

drafting the article or revising it critically for important intellectual 

content; and (3) final approval of the version to be published. Authors 

should meet conditions 1, 2, and 3. 

Institution: Author names should be given first, then the complete 

name of institution, city, province and postcode. For example, Xu- 

Chen Zhang, Li-Xin Mei, Department of Pathology, Chengde 

Medical College, Chengde 067000, Hebei Province, China. One 

author may be represented from two institutions, for example, George 

Sgourakis, Department of General, Visceral, and Transplan- 


tation Surgery, Essen 45122, Germany; George Sgourakis, 2nd 

Surgical Department, Korgialenio-Benakio Red Cross Hospital, 

Athens 15451, Greece 

Author contributions: The format of this section should be: 

Author contributions: Wang CL and Liang L contributed equally 

to this work; Wang CL, Liang L, Fu JF, Zou CC, Hong F and Wu 

XM designed the research; Wang CL, Zou CC, Hong F and Wu 

XM performed the research; Xue JZ and Lu JR contributed new 

reagents/analytic tools; Wang CL, Liang L and Fu JF analyzed the 

data; and Wang CL, Liang L and Fu JF wrote the paper. 

Supportive foundations: The complete name and number of 

supportive foundations should be provided, e.g., Supported by 

National Natural Science Foundation of China, No. 30224801 

Correspondence to: Only one corresponding address should 

be provided. Author names should be given first, then author 

title, affiliation, the complete name of institution, city, postcode, 

province, country, and email. All the letters in the email should be 

in lower case. A space interval should be inserted between country 

name and email address. For example, Montgomery Bissell, MD, 

Professor of Medicine, Chief, Liver Center, Gastroenterology 

Division, University of California, Box 0538, San Francisco, CA 

94143, United States. montgomery.bissell@ucsf.edu 

Telephone and fax: Telephone and fax should consist of +, 

country number, district number and telephone or fax number, e.g., 

Telephone: +86-10-59080039 Fax: +86-10-85381893 

Peer reviewers: All articles received are subject to peer review. 

Normally, three experts are invited for each article. Decision for 

acceptance is made only when at least two experts recommend 

an article for publication. Reviewers for accepted manuscripts are 

acknowledged in each manuscript, and reviewers of articles which 

were not accepted will be acknowledged at the end of each issue. 

To ensure the quality of the articles published in WJD, reviewers 

of accepted manuscripts will be announced by publishing the 

name, title/position and institution of the reviewer in the footnote 

accompanying the printed article. For example, reviewers: Professor 

Jing-Yuan Fang, Shanghai Institute of Digestive Disease, Shanghai, 

Affiliated Renji Hospital, Medical Faculty, Shanghai Jiaotong 

University, Shanghai, China; Professor Xin-Wei Han, Department 

of Radiology, The First Affiliated Hospital, Zhengzhou University, 

Zhengzhou, Henan Province, China; and Professor Anren Kuang, 

Department of Nuclear Medicine, Huaxi Hospital, Sichuan University, 

Chengdu, Sichuan Province, China. 

Abstract 

There are unstructured abstracts (no more than 256 words) and 

structured abstracts (no more than 480). The specific requirements 

for structured abstracts are as follows: 

An informative, structured abstracts of no more than 480 

words should accompany each manuscript. Abstracts for original 

contributions should be structured into the following sections. AIM 

(no more than 20 words): Only the purpose should be included. 

Please write the aim as the form of “To investigate/study/…; 

MATERIALS AND METHODS (no more than 140 words); 

RESULTS (no more than 294 words): You should present P values 

where appropriate and must provide relevant data to illustrate 

how they were obtained, e.g. 6.92 ± 3.86 vs 3.61 ± 1.67, P < 0.001; 

CONCLUSION (no more than 26 words). 

Key words 

Please list 5-10 key words, selected mainly from Index Medicus, which 

reflect the content of the study. 

Text 

For articles of these sections, original articles, rapid communication 

and case reports, the main text should be structured into 

the following sections: INTRODUCTION, MATERIALS AND 

WJD|www.wjgnet.com III 


METHODS, RESULTS and DISCUSSION, and should include 

appropriate Figures and Tables. Data should be presented in the 

main text or in Figures and Tables, but not in both. The main 

text format of these sections, editorial, topic highlight, case 

report, letters to the editors, can be found at: http://www.wjgnet. 

com/1948-9358/g_info_20100107165233.htm. 

Illustrations 

Figures should be numbered as 1, 2, 3, etc., and mentioned clearly 

in the main text. Provide a brief title for each figure on a separate 

page. Detailed legends should not be provided under the figures. 

This part should be added into the text where the figures are 

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files (in tiff, eps, jpeg formats) at high-resolution. Examples can 

be found at: http://www.wjgnet.com/1007-9327/13/4520. 

pdf; http://www.wjgnet.com/1007-9327/13/4554.pdf; 

http://www.wjgnet.com/1007-9327/13/4891.pdf; http:// 

www.wjgnet.com/1007-9327/13/4986.pdf; http://www. 

wjgnet.com/1007-9327/13/4498.pdf. Keeping all elements 

compiled is necessary in line-art image. Scale bars should be 

used rather than magnification factors, with the length of the bar 

defined in the legend rather than on the bar itself. File names should 

identify the figure and panel. Avoid layering type directly over 

shaded or textured areas. Please use uniform legends for the 

same subjects. For example: Figure 1 Pathological changes in 

atrophic gastritis after treatment. A: ...; B: ...; C: ...; D: ...; E: ...; F: ...; 

G: …etc. It is our principle to publish high resolution-figures for the 

printed and E-versions. 

Tables 

Three-line tables should be numbered 1, 2, 3, etc., and mentioned 

clearly in the main text. Provide a brief title for each table. 

Detailed legends should not be included under tables, but rather 

added into the text where applicable. The information should 

complement, but not duplicate the text. Use one horizontal line 

under the title, a second under column heads, and a third below 

the Table, above any footnotes. Vertical and italic lines should be 

omitted. 

Notes in tables and illustrations 

Data that are not statistically significant should not be noted. a P < 

0.05, b P < 0.01 should be noted (P > 0.05 should not be noted). If 

there are other series of P values, c P < 0.05 and d P < 0.01 are used. 

A third series of P values can be expressed as e P < 0.05 and f P < 0.01. 

Other notes in tables or under illustrations should be expressed as 

1 F, 2 F, 3 F; or sometimes as other symbols with a superscript (Arabic 

numerals) in the upper left corner. In a multi-curve illustration, each 

curve should be labeled with ●, ○, ■, □, ▲, △, etc., in a certain 

sequence. 

Acknowledgments 

Brief acknowledgments of persons who have made genuine contributions 

to the manuscript and who endorse the data and conclusions 

should be included. Authors are responsible for obtaining 

written permission to use any copyrighted text and/or illustrations. 

REFERENCES 

Coding system 

The author should number the references in Arabic numerals 

according to the citation order in the text. Put reference numbers 

in square brackets in superscript at the end of citation content or 

after the cited author’s name. For citation content which is part of 

the narration, the coding number and square brackets should be 

typeset normally. For example, “Crohn’s disease (CD) is associated 

with increased intestinal permeability [1,2] ”. If references are cited 

directly in the text, they should be put together within the text, for 

example, “From references [19,22-24] , we know that...” 

When the authors write the references, please ensure that 

the order in text is the same as in the references section, and also 

ensure the spelling accuracy of the first author’s name. Do not list 

the same citation twice. 



PMID and DOI 

Pleased provide PubMed citation numbers to the reference list, 

e.g. PMID and DOI, which can be found at http://www.ncbi. 

nlm.nih.gov/sites/entrez?db=pubmed and http://www.crossref. 

org/SimpleTextQuery/, respectively. The numbers will be used in 

E-version of this journal. 

Style for journal references 

Authors: the name of the first author should be typed in boldfaced 

letters. The family name of all authors should be typed with 

the initial letter capitalized, followed by their abbreviated first 

and middle initials. (For example, Lian-Sheng Ma is abbreviated 

as Ma LS, Bo-Rong Pan as Pan BR). The title of the cited article 

and italicized journal title (journal title should be in its abbreviated 

form as shown in PubMed), publication date, volume number 

(in black), start page, and end page [PMID: 11819634 DOI: 

10.3748/wjg.13.5396]. 

Style for book references 

Authors: the name of the first author should be typed in bold-faced 

letters. The surname of all authors should be typed with the initial 

letter capitalized, followed by their abbreviated middle and first 

initials. (For example, Lian-Sheng Ma is abbreviated as Ma LS, Bo- 

Rong Pan as Pan BR) Book title. Publication number. Publication 

place: Publication press, Year: start page and end page. 

Format 

Journals 

English journal article (list all authors and include the PMID where 

applicable) 

1 Jung EM, Clevert DA, Schreyer AG, Schmitt S, Rennert J, 

Kubale R, Feuerbach S, Jung F. Evaluation of quantitative 

contrast harmonic imaging to assess malignancy of liver 

tumors: A prospective controlled two-center study. World J 

Gastroenterol 2007; 13: 6356-6364 [PMID: 18081224 DOI: 

10.3748/wjg.13.6356] 

Chinese journal article (list all authors and include the PMID where 

applicable) 

2 Lin GZ, Wang XZ, Wang P, Lin J, Yang FD. Immunologic 

effect of Jianpi Yishen decoction in treatment of Pixudiarrhoea. 

Shijie Huaren Xiaohua Zazhi 1999; 7: 285-287 

In press 

3 Tian D, Araki H, Stahl E, Bergelson J, Kreitman M. Signature 

of balancing selection in Arabidopsis. Proc Natl Acad Sci USA 

2006; In press 

Organization as author 

4 Diabetes Prevention Program Research Group. Hypertension, 

insulin, and proinsulin in participants with impaired 

glucose tolerance. Hypertension 2002; 40: 679-686 [PMID: 

12411462 PMCID:2516377 DOI:10.1161/01.HYP.00000 

35706.28494.09] 

Both personal authors and an organization as author 

5 Vallancien G, Emberton M, Harving N, van Moorselaar RJ; 

Alf-One Study Group. Sexual dysfunction in 1, 274 European 

men suffering from lower urinary tract symptoms. J Urol 

2003; 169: 2257-2261 [PMID: 12771764 DOI:10.1097/01. 

ju.0000067940.76090.73] 

No author given 

6 21st century heart solution may have a sting in the tail. 

BMJ 2002; 325: 184 [PMID: 12142303 DOI:10.1136/ 

bmj.325.7357.184] 

Volume with supplement 

7 Geraud G, Spierings EL, Keywood C. Tolerability and safety 

of frovatriptan with short- and long-term use for treatment 

of migraine and in comparison with sumatriptan. Headache 

2002; 42 Suppl 2: S93-99 [PMID: 12028325 DOI:10.1046/ 

j.1526-4610.42.s2.7.x] 

Issue with no volume 

8 Banit DM, Kaufer H, Hartford JM. Intraoperative frozen 

section analysis in revision total joint arthroplasty. Clin Orthop 

WJD|www.wjgnet.com IV 

Relat Res 2002; (401): 230-238 [PMID: 12151900 DOI:10.109 

7/00003086-200208000-00026] 

No volume or issue 

9 Outreach: Bringing HIV-positive individuals into care. HRSA 

Careaction 2002; 1-6 [PMID: 12154804] 

Books 

Personal author(s) 

10 Sherlock S, Dooley J. Diseases of the liver and billiary system. 

9th ed. Oxford: Blackwell Sci Pub, 1993: 258-296 

Chapter in a book (list all authors) 

11 Lam SK. Academic investigator’s perspectives of medical 

treatment for peptic ulcer. In: Swabb EA, Azabo S. Ulcer 

disease: investigation and basis for therapy. New York: Marcel 

Dekker, 1991: 431-450 

Author(s) and editor(s) 

12 Breedlove GK, Schorfheide AM. Adolescent pregnancy. 2nd 

ed. Wieczorek RR, editor. White Plains (NY): March of Dimes 

Education Services, 2001: 20-34 

Conference proceedings 

13 Harnden P, Joffe JK, Jones WG, editors. Germ cell tumours V. 

Proceedings of the 5th Germ cell tumours Conference; 2001 

Sep 13-15; Leeds, UK. New York: Springer, 2002: 30-56 

Conference paper 

14 Christensen S, Oppacher F. An analysis of Koza's computational 

effort statistic for genetic programming. In: Foster 

JA, Lutton E, Miller J, Ryan C, Tettamanzi AG, editors. 

Genetic programming. EuroGP 2002: Proceedings of the 5th 

European Conference on Genetic Programming; 2002 Apr 

3-5; Kinsdale, Ireland. Berlin: Springer, 2002: 182-191 

Electronic journal (list all authors) 

15 Morse SS. Factors in the emergence of infectious diseases. 

Emerg Infect Dis serial online, 1995-01-03, cited 1996-06-05; 

1(1): 24 screens. Available from: URL: http://www.cdc.gov/ 

ncidod/eid/index.htm 

Patent (list all authors) 

16 Pagedas AC, inventor; Ancel Surgical R&D Inc., assignee. 

Flexible endoscopic grasping and cutting device and 

positioning tool assembly. United States patent US 200201 

03498. 2002 Aug 1 

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Statistical expression 

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Use SI units. For example: body mass, m (B) = 78 kg; blood 

pressure, p (B) = 16.2/12.3 kPa; incubation time, t (incubation) = 

96 h, blood glucose concentration, c (glucose) 6.4 ± 2.1 mmol/L; 

blood CEA mass concentration, p (CEA) = 8.6 24.5 mg/L; CO 2 

volume fraction, 50 mL/L CO 2, not 5% CO 2; likewise for 40 g/L 

formaldehyde, not 10% formalin; and mass fraction, 8 ng/g, etc. 

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and Abbreviations: A Guide for Biological and Medical Editors and 

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Quantities: t time or temperature, c concentration, A area, l length, 

m mass, V volume. 

Genotypes: gyrA, arg 1, c myc, c fos, etc. 

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