Serum amylase levels are decreased in Chinese non-alcoholic fatty liver disease patients
© Yao et al.; licensee BioMed Central Ltd. 2014
Received: 30 July 2014
Accepted: 1 December 2014
Published: 7 December 2014
Low serum amylase levels have been reported in patients with metabolic syndrome (MS), diabetes, and asymptomatic non-alcoholic fatty liver disease (NAFLD). However, no study has yet indicated the serum amylase levels in NAFLD with MS. The aim of the present study was to evaluate serum amylase levels in NAFLD patients with and without MS, and to explore a possible association between serum amylase levels with the components of MS and the degree of hepatic fibrosis in NAFLD patients.
Our study included 713 NAFLD participants (180 females and 533 males) and 304 healthy control participants (110 females and 194 males). The diagnosis of NAFLD was based on ultrasonography, and advanced fibrosis was assessed by the FIB-4 index.
Serum amylase levels were significantly lower in NAFLD patients with MS compared with NAFLD patients without MS and healthy controls (42, 45, and 53 IU/L, respectively). The serum amylase levels of patients with elevated glucose, elevated triglycerides, and low high density lipoprotein cholesterol patients were significantly lower than in case of normal parameters (both p < 0.05). Multivariate logistic regression analysis showed that a relative serum amylase level increase was an independent factor predicting advanced fibrosis (FIB-4 ≥1.3) in NAFLD participants (OR: 1.840, 95% CI: 1.117-3.030, p=0.017).
Compared with NAFLD patients without MS and healthy controls, serum amylase levels were significantly lower in NAFLD patients with MS. Moreover, a relative serum amylase increase may be an independent factor of more advanced hepatic fibrosis.
KeywordsNAFLD Amylase Metabolic syndrome Fibrosis
NAFLD is a clinico-pathological condition and corresponds to a disease spectrum encompassing simple steatosis, nonalcoholic steatohepatitis (NASH) with or without cirrhosis, and hepatocellular carcinoma (HCC) [1–5]. Approximately, 5% to 20% of patients with NAFLD develop NASH, which progresses to advanced fibrosis in 10% to 20% of cases and cirrhosis in nearly 5% of cases [3, 4, 6]. The prevalence of NAFLD in the general population in Europe is estimated to be 20% to 30% , and 12% to 24% in Asia . In Shanghai, Guangdong, and Hong Kong (China) it has been reported to be 17%, 15%, and 16%, respectively [9–11].
NAFLD is closely associated with obesity, type 2 diabetes mellitus, metabolic syndrome (MS), insulin resistance, hypertension and dyslipidemia . However, it is worth noting that nonalcoholic steatohepatitis also induces and enhances insulin resistance, leading to a vicious cycle . Patients with NAFLD exhibit increased liver-related complications and mortality . NAFLD has become a significant public health burden owing to hepatic and extrahepatic morbidity and mortality [2, 13].
The gold standard of hepatic fibrosis remains liver biopsy, but this technique is potentially risky and expensive . Adams et al.  found that the FIB-4 index was the most appropriate indicator for advanced fibrosis prediction compared with other non-invasive fibrosis models. Likewise, Xun et al. found that the FIB-4 index, although slightly less accurate than liver biopsy, can be used to evaluate liver fibrosis in Chinese NAFLD patients .
Elevated serum amylase remains the most widely used biochemical test for the diagnosis of acute pancreatitis with serum amylase levels ≥ 3 times the normal upper limit [16, 17]. Low serum amylase has been reported in diffuse pancreas destruction and/or atrophic pancreas tissue [18–21]. Recently, other studies [22–26] have shown that lower serum amylase levels are associated with an increased prevalence for MS, diabetes, and NAFLD in asymptomatic adults and suggested that insulin resistance and fat accumulation may result in a decrease of serum amylase levels. Morever, Nakajima K et al. indicated that low serum amylase may be a marker for moderate or severe NAFLD .
Since NAFLD and MS can each lead to the decrease of serum amylase levels, we hypothesized that the combination of NAFLD and MS could further accentuate this decrease. Therefore, we aimed to explore the diagnostic value of serum amylase levels in the context of NAFLD with and without MS.
Materials and methods
This study was approved by the ethics committee of the First Affiliated Hospital of the Medical College at Zhejiang University in China and was performed in accordance with the Helsinki Declaration. Written informed consent was obtained from each participant at the time of enrollment.
Inclusion and exclusion criteria
The diagnosis of MS was based on the Chinese Diabetes Society (CDS) classification when any three or more of the following five components were present : (i) body mass index (BMI) ≥ 25 kg/m2 ; (ii) fasting plasma glucose (FPG) ≥ 6.1 mmol/L or taking anti-diabetic medications; (iii) blood pressure ≥ 140/90 mmHg or taking anti-hypertensive medications; (iv) triglycerides (TG) ≥ 1.7 mmol/L; and (v) high density lipoprotein cholesterol (HDL-c) < 0.9 mmol/L in males or < 1.0 mmol/L in females. Diabetes diagnosis was based on the 2010 International Expert Committee (IEC) and the American Diabetes Association (ADA) guidelines . Diabetes mellitus was identified according to the following components: HbA1c ≥ 6.5%; random plasma glucose or 2-hour glucose ≥ 11.1 mmol/L; and fasting plasma glucose ≥ 7.0 mmol/dL. NAFLD was diagnosed according to the guidelines established for the diagnosis and treatment of NAFLD issued by the Chinese National Consensus Workshop on Nonalcoholic Fatty Liver Disease . The diagnosis of NAFLD was based on ultrasonography finding of hepatic steatosis as diagnosed by characteristic echo patterns using a Toshiba Nemio 20 sonography machine with a 3.5-MHz probe (Toshiba, Tokyo, Japan). Hepatic steatosis was identified according to characteristics of the echo patterns, such as ultrasound beam attenuation, diffuse hyper echogenicity of the liver, and poor visualization of intra hepatic structures . Patients with any of the following conditions in their medical history were excluded from the study: (i) alcohol consumption greater than 140 g/week for men and 70 g/week for women; (ii) viral hepatitis or autoimmune hepatitis; or (iii) hepatotoxic medications .
Healthy control participants were selected from clinically asymptomatic participants after exclusion of the following conditions: kidney, cardiovascular, liver, respiratory, and gynecologic diseases, impaired glucose tolerance, arterial hypertension, body mass index (BMI) ≥ 28 kg/m2 or ≤ 18.5 kg/m2, abnormal triglycerides (≥ 2.26 mmol/L) or total cholesterol (≥ 6.22 mmol/L), smoking (≥ 20 cigarettes per day) or drinking (≥ 30 g per day), the presence of pregnancy or lactation, surgery during the previous six months, acute or chronic infections, history of malignancy or drug intake within the previous two weeks.
Our study included 713 NAFLD participants (180 females [50.8 ± 13.4 years] and 533 males [44.5 ± 11.2 years]) and 304 healthy control participants (110 females [46.7 ± 11.5 years] and 194 males [46.0 ± 10.1 years]) who underwent a general health checkup in the context of the Health Care Centre at the First Affiliated Hospital of Medical College of Zhejiang University between September 2013 and February 2014. We divided the NAFLD participants into two groups: (1) NAFLD with MS (N = 300) and (2) NAFLD without MS (N = 413).
Clinical and biochemical assessment
All study participants were subjected to the following biochemical determinations: serum amylase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), γ-glutamyltransferase ( γ-GT), FPG, creatinine (Cr), uric acid (UA), high sensitivity C reactive protein (hsCRP), platelet count (PLT), and glycated hemoglobin A1C (HbA1C) measurements.
All venous blood samples were obtained in the morning following a 12 h fast. Serum amylase, ALT, AST, TG, TC, HDL-c, LDL-c, γ -GT, and FPG were determined using a Hitachi DDP autoanalyzer (Hitachi Corp, Ibaragi, Japan). ALT, AST, TG, TC, γ -GT, and FPG levels were measured using Roche reagents (Roche Diagnostics, Indianapolis, USA). Serum amylase, HDL-c and LDL-c levels were measured using Shenshuoyoufu reagents (Shenshuoyoufu, Shanghai, China). HbA1c was determined on a Sysmex HbA1c analyzer G8 (Sysmex corporation, Kobe, Japan) using Sysmex reagents. PLT count was determined using a Sysmex XE-2100 automated hematology analyzer (Sysmex Corp, Kobe, Japan).
Evaluation of liver fibrosis
No liver biopsy was performed. Instead, a non-invasive FIB-4 index of ≥1.3 was utilized to evaluate advanced fibrosis in NAFLD patients (defined as portal fibrosis with many septa and cirrhosis [14, 32]), according to studies by Xun et al. and Kim et al. [15, 33].
Baseline characteristics of study participants
NAFLD (n = 713)
Healthy controls (n = 304)
Without MS (n = 413)
With MS (n = 300)
45.9 ± 12.1
46.3 ± 12.2
46.3 ± 10.6
25.9 ± 2.7*#
26.8 ± 2.5*
22.8 ± 2.6
132 ± 16*
120 ± 14
80 ± 11*
81 ± 11*
78 ± 10
4.91 ± 0.91*#
5.06 ± 1.06*
4.51 ± 0.63
1.24 ± 0.34*#
1.01 ± 0.24*
1.27 ± 0.28
2.74 ± 0.57*#
2.62 ± 0.64*
2.49 ± 0.44
73 (37–104) #
233 ± 52*
231 ± 55*
214 ± 41
Characteristics of NAFLD participants according to serum amylase quartile levels
46.1 ± 12.1
43.0 ± 11.0
45.5 ± 11.0
45.9 ± 11.9
50.5 ± 12.1
26.2 ± 2.6
26.7 ± 3.0
26.3 ± 2.6
26.2 ± 2.5
25.6 ± 2.2
131 ± 16
132 ± 16
131 ± 15
131 ± 16
132 ± 17
4.97 ± 0.98
4.92 ± 0.90
5.07 ± 1.16
4.97 ± 0.95
4.92 ± 0.89
1.14 ± 0.32
1.13 ± 0.45
1.13 ± 0.27
1.16 ± 0.26
1.15 ± 0.24
2.69 ± 0.61
2.63 ± 0.57
2.73 ± 0.64
2.72 ± 0.62
2.69 ± 0.60
233 ± 53
241 ± 50
228 ± 51
233 ± 52
228 ± 59
FIB-4 ≥ 1.3 (%)
Baseline characteristics of study participants
Characteristics of NAFLD participants according to the quartile of amylase levels
We divided NAFLD participants into four groups: Q1 (lowest), Q2, Q3, and Q4 (highest) according to the quartile of their serum amylase levels. Across increasing serum amylase quartiles, BMI, SBP, DBP, TG, FPG, and HsCRP levels were gradually decreased, while age, FIB-4 values and the incidence of FIB-4 ≥ 1.3 gradually increased. Age, BMI, SBP, DBP, ALT, γ-GT, TG, FPG, Cr, UA, HbA1C, HsCRP, FIB-4 values, and the incidence of FIB-4 ≥ 1.3 and MS were significantly different between the four groups.
Correlation analysis between serum amylase levels and other variables
The correlation between serum amylase and other covariates
Association of serum amylase and the incidence of advanced fibrosis in NAFLD participants
Odds ratios for advanced fibrosis in NAFLD participants according to serum amylase quartiles levels (Q4 vs. Q1)
Odds ratio (95% CI)
The present cross-sectional study showed that NAFLD patients with MS had lower serum amylase levels than healthy controls and NAFLD patients without MS. The prevalence of MS in NAFLD patients was higher in the lower serum amylase levels group compared to the other three groups. Moreover, serum amylase levels of NAFLD patients with elevated FPG, elevated TG, or reduced HDL-c levels were lower than in NAFLD patients with normal FPG, TG, or HDL-c levels. In addition, serum amylase levels were increased, as an independent factor, in NAFLD patients with advanced liver fibrosis. These results provide evidence for a significant association between low serum amylase levels and NAFLD with MS.
The significant association between low serum amylase levels and NAFLD with MS suggest that MS and NAFLD may both contribute to the decrease in serum amylase levels. The potential mechanism accounting for the association between NAFLD and low serum amylase levels may be insulin resistance and fatty pancreas. Insulin resistance is known to be one of the key components of MS and it eventually leads to the development of type 2 diabetes, and NAFLD and NASH are tightly associated with insulin resistance [22–26]. In humans, a strong relationship exists between hepatic fat accumulation and whole-body insulin resistance. Morever, insulin resistance may enhance hepatic fat accumulation by increasing free fatty acid delivery and by stimulating the anabolic process due to hyperinsulinemia . In 2014, Gruben et al.  found that hepatic lipid accumulation and inflammation could be the main drivers of hepatic insulin resistance. The association between lipid accumulation (such as diacylglycerol and TG) and hepatic insulin resistance has been observed in some animal models [36, 37]. Although the physiological liver maintains blood glucose homeostasis by gluconeogenesis and insulin inhibition, in hepatic insulin resistance, this inhibition is no longer effective . Diacylglycerol is used for the formation of TG, a process catalyzed by the enzyme diacylglycerol acyltransferase 2 (Dgat2), and leading to protein kinase Cϵ activation (PKCϵ), which in turn results in hepatic insulin resistance [36, 39]. Reduction of diacylglycerol by down-regulation of Dgat2 can improve glucose intolerance and restore hepatic insulin signaling in mice . Main inflammatory pathways, nuclear factor κB (NF-κB) activation regulated by the IKK2 or TNFR signaling cascade, c-Jun NH2-terminal kinase (JNK) activation, and Kupffer cell depletion are involved in the development of insulin resistance [40–42].
Some studies reported the associations between low serum amylase levels and MS, diabetes, NAFLD, cardiometabolic aspects, and insulin resistance after adjustement for relevant confounding factors [23, 25, 43, 44]. These associations may be related to insulin resistance and systemic ectopic fat deposition in the pancreas in asymptomatic adults . In rat models, long-term exposure to a high-fat diet induced both interlobular and intralobular fat accumulation, pancreas fibrosis, and damaged the normal pancreatic architecture and islets . In human studies, fatty pancreas is closely associated with increased insulin resistance, metabolic syndrome, and fatty liver . NAFLD and MS have been reported to be associated with fatty pancreas [47, 48]. Some previous studies have indicated that fatty pancreas may lead to exocrine-endocrine dysfunction and to a loss of β-cell mass and function [25, 49], which may cause the decrease of serum amylase . Wu et al. found that serum amylase values were significantly lower for the fatty pancreas as compared to normal pancreas . Lee et al., and our previous study, also found that low serum amylase levels were associated with an increased prevalence of MS [22, 24]. Our results are consistent with the studies of Nakajima et al. [23, 25] who also suggested that low serum amylase levels may be associated with NAFLD and MS through insulin resistance and fatty pancreas.
Liver biopsy is the gold standard for determining the presence and degree of hepatic fibrosis in NAFLD patients, but liver biopsy has several shortcomings . The identification of advanced fibrosis in NAFLD patients is of utmost important in clinical practice . Therefore, non-invasive fibrosis models, such as APRI, BARD, Hepascore, Fibrotest, FIB4, AAR, and NIKEI, were developed for evaluating advanced fibrosis in NAFLD patients [14, 15, 51]. Xun et al., in China, showed that a FIB-4 index ≥ 1.3 for evaluating advanced fibrosis was better than the other non-invasive models and was suitable for evaluating advanced fibrosis in Chinese NAFLD patients . Therefore, we chose to use this index for evaluating advanced fibrosis in our study.
NAFPD may lead to nonalcoholic steatopancreatitis (NASP), and pancreatic steatosis has also become increasingly and may affect the progression of NAFLD [48, 52, 53]. Patel et al. found that pancreatic fat content was lower in NAFLD patients who had advanced liver fibrosis as assessed by novel magnetic resonance imaging technology . Although serum amylase levels in NAFLD patients were globally decreased, those NAFLD patients with advanced fibrosis had relatively higher serum amylase levels for less pancreatic fat content. Similar to our results, Nakajima et al. suggested that low serum amylase was associated with NAFLD independently of MS, diabetes and obesity and may be an independent marker for moderate/severe NAFLD in asymptomatic adults . However, in their study, it appears difficult to evaluate the association between serum amylase and hepatic fibrosis since the study included a large number of non-obese individuals with only a small proportion having MS and diabetes, which may have resulted in a lower likelihood of advanced hepatic fibrosis.
Several limitations of our study should be mentioned. First, it is a cross-sectional observational study that cannot definitively comment on causality or temporal association between low serum amylase and NAFLD. Second, NAFLD diagnosis was based not on the gold standard of liver biopsy, but on ultrasonography, which may not be sensitive enough to detect mild steatosis. Third, for evaluating advanced fibrosis, we did not use liver biopsy but the surrogate FIB-4 index ≥ 1.3 ; it remains possible that some patients were inadequately classified. Finally, we only studied Chinese NAFLD patients and our results may not fully apply to other ethnic populations.
This work was financially supported by grants from the Department of Education Foundation of Zhejiang Province, China (No. Y201330146), the Science Foundation of the Health Bureau of Zhejiang Province (No. 2013KYB116), and the National Natural Science Foundation of China (No. 81370008).
- Wang L, Li YM, He FC, Jiang Y: Nonalcoholic fatty liver disease and immune disturbance. Zhonghua Gan Zang Bing Za Zhi. 2008, 16 (11): 870-871. ChinesePubMedGoogle Scholar
- Nascimbeni F, Pais R, Bellentani S, Day CP, Ratziu V, Loria P, Lonardo A: From NAFLD in clinical practice to answers from guidelines. J Hepatol. 2013, 59 (4): 859-871. 10.1016/j.jhep.2013.05.044View ArticlePubMedGoogle Scholar
- Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M: Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology. 2002, 123 (1): 134-140. 10.1053/gast.2002.34168View ArticlePubMedGoogle Scholar
- Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ: The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American association for the study of liver diseases, American college of gastroenterology, and the American gastroenterological association. Hepatology. 2012, 55 (6): 2005-2023. 10.1002/hep.25762View ArticlePubMedGoogle Scholar
- Vernon G, Baranova A, Younossi ZM: Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011, 34 (3): 274-285. 10.1111/j.1365-2036.2011.04724.xView ArticlePubMedGoogle Scholar
- Weiß J, Rau M, Geier A: Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. Dtsch Arztebl Int. 2014, 111 (26): 447-452.PubMed CentralPubMedGoogle Scholar
- Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F: The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013, 58 (3): 593-608. 10.1016/j.jhep.2012.12.005View ArticlePubMedGoogle Scholar
- Fan JG, Saibara T, Chitturi S, Kim BI, Sung JJ, Chutaputti A: Asia-Pacific Working Party for NAFLD: What are the risk factors and settings for non-alcoholic fatty liver disease in Asia-Pacific?. J Gastroenterol Hepatol. 2007, 22 (6): 794-800. 10.1111/j.1440-1746.2007.04952.xView ArticlePubMedGoogle Scholar
- Fan JG, Zhu J, Li XJ, Chen L, Li L, Dai F, Li F, Chen SY: Prevalence of and risk factors for fatty liver in a general population of Shanghai, China. J Hepatol. 2005, 43 (3): 508-514. 10.1016/j.jhep.2005.02.042View ArticlePubMedGoogle Scholar
- Zhou YJ, Li YY, Nie YQ, Ma JX, Lu LG, Shi SL, Chen MH, Hu PJ: Prevalence of fatty liver disease and its risk factors in the population of South China. World J Gastroenterol. 2007, 13 (47): 6419-6424. 10.3748/wjg.v13.i47.6419PubMed CentralView ArticlePubMedGoogle Scholar
- Wong VW, Chan HL, Hui AY, Chan KF, Liew CT, Chan FK, Sung JJ: Clinical and histological features of non-alcoholic fatty liver disease in Hong Kong Chinese. Aliment Pharmacol Ther. 2004, 20 (1): 45-49. 10.1111/j.1365-2036.2004.02012.x.View ArticlePubMedGoogle Scholar
- Hurjui DM, Niţă O, Graur LI, Mihalache L, Popescu DS, Graur M: The central role of the non alcoholic fatty liver disease in metabolic syndrome. Rev Med Chir Soc Med Nat Iasi. 2012, 116 (2): 425-431.PubMedGoogle Scholar
- Lonardo A, Sookoian S, Chonchol M, Loria P, Targher G: Cardiovascular and systemic risk in nonalcoholic fatty liver disease - atherosclerosis as a major player in the natural course of NAFLD. Curr Pharm Des. 2013, 19 (29): 5177-5192. 10.2174/1381612811319290003View ArticlePubMedGoogle Scholar
- Adams LA, George J, Bugianesi E, Rossi E, De Boer WB, van der Poorten D, Ching HL, Bulsara M, Jeffrey GP: Complex non-invasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2011, 26 (10): 1536-1543. 10.1111/j.1440-1746.2011.06774.xView ArticlePubMedGoogle Scholar
- Xun YH, Fan JG, Zang GQ, Liu H, Jiang YM, Xiang J, Huang Q, Shi JP: Suboptimal performance of simple noninvasive tests for advanced fibrosis in Chinese patients with nonalcoholic fatty liver disease. J Dig Dis. 2012, 13 (11): 588-595. 10.1111/j.1751-2980.2012.00631.xView ArticlePubMedGoogle Scholar
- Yang RW, Shao ZX, Chen YY, Yin Z, Wang WJ: Lipase and pancreatic amylase activities in diagnosis of acute pancreatitis in patients with hyperamylasemia. Hepatobiliary Pancreat Dis Int. 2005, 4 (4): 600-603.PubMedGoogle Scholar
- Wu BU, Banks PA: Clinical management of patients with acute pancreatitis. Gastroenterology. 2013, 144 (6): 1272-1281. 10.1053/j.gastro.2013.01.075View ArticlePubMedGoogle Scholar
- Domínguez-Muñoz JE, Pieramico O, Büchler M, Malfertheiner P: Ratios of different serum pancreatic enzymes in the diagnosis and staging of chronic pancreatitis. Digestion. 1993, 54: 231-236. 10.1159/000201042View ArticlePubMedGoogle Scholar
- Maruyama K, Takahashi H, Okuyama K, Yokoyama A, Nakamura Y, Kobayashi Y, Ishii H: Low serum amylase levels in drinking alcoholics. Alcohol Clin Exp Res. 2003, 27: 16S-21S. 10.1097/01.ALC.0000078827.46112.76View ArticlePubMedGoogle Scholar
- Dandona P, Freedman DB, Foo Y, Rosalki SB, Beckett AG: Exocrine pancreatic function in diabetes mellitus. J Clin Pathol. 1984, 37: 302-306. 10.1136/jcp.37.3.302PubMed CentralView ArticlePubMedGoogle Scholar
- Aughsteen AA, Abu-Umair MS, Mahmoud SA: Biochemical analysis of serum pancreatic amylase and lipase enzymes in patients with type 1 and type 2 diabetes mellitus. Saudi Med J. 2005, 26: 73-77.PubMedGoogle Scholar
- Lee JG, Park SW, Cho BM, Lee S, Kim YJ, Jeong DW, Yi YH, Cho YH: Serum amylase and risk of the metabolic syndrome in Korean adults. Clin Chim Acta. 2011, 412 (19–20): 1848-1853.View ArticlePubMedGoogle Scholar
- Nakajima K, Nemoto T, Muneyuki T, Kakei M, Fuchigami H, Munakata H: Low serum amylase in association with metabolic syndrome and diabetes: a community-based study. Cardiovasc Diabetol. 2011, 10: 34- 10.1186/1475-2840-10-34PubMed CentralView ArticlePubMedGoogle Scholar
- Zhao Y, Zhang J, Zhang J, Wu J, Chen Y: Metabolic syndrome and diabetes are associated with low serum amylase in a Chinese asymptomatic population. Scand J Clin Lab Invest. 2014, 74 (3): 235-239. 10.3109/00365513.2013.878469View ArticlePubMedGoogle Scholar
- Nakajima K, Oshida H, Muneyuki T, Saito M, Hori Y, Fuchigami H, Kakei M, Munakata H: Independent association between low serum amylase and non-alcoholic fatty liver disease in asymptomatic adults: a cross-sectional observational study. BMJ Open. 2013, 3 (1): e002235-PubMed CentralView ArticlePubMedGoogle Scholar
- Wu WC, Wang CY: Association between non-alcoholic fatty pancreatic disease (NAFPD) and the metabolic syndrome: case–control retrospective study. Cardiovasc Diabetol. 2013, 12: 77- 10.1186/1475-2840-12-77PubMed CentralView ArticlePubMedGoogle Scholar
- Sun X, Du T, Huo R, Yu X, Xu L: I mpact of HbA1c criterion on the definition of glycemic component of the metabolic syndrome: the China health and nutrition survey 2009. BMC Public Health. 2013, 13: 1045- 10.1186/1471-2458-13-1045PubMed CentralView ArticlePubMedGoogle Scholar
- Olson DE, Rhee MK, Herrick K, Ziemer DC, Twombly JG, Phillips LS: Screening for diabetes and pre-diabetes with proposed A1C-based diagnostic criteria. Diabetes Care. 2010, 33 (10): 2184-2189. 10.2337/dc10-0433PubMed CentralView ArticlePubMedGoogle Scholar
- Zeng MD, Fan JG, Lu LG, Li YM, Chen CW, Wang BY, Mao YM: Chinese national consensus workshop on nonalcoholic fatty liver disease: guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases. J Dig Dis. 2008, 9 (2): 108-112. 10.1111/j.1751-2980.2008.00331.xView ArticlePubMedGoogle Scholar
- Zhang J, Zhao Y, Xu C, Hong Y, Lu H, Wu J, Chen Y: Association between serum free fatty acid levels and nonalcoholic fatty liver disease: a cross-sectional study. Sci Rep. 2014, 25 (4): 5832-Google Scholar
- Jian-gao F: Chinese liver disease association: guidelines for management of nonalcoholic fatty liver disease: an updated and revised edition. Zhonghua Gan Zang Bing Za Zhi. 2010, 18 (3): 163-166.PubMedGoogle Scholar
- Chen B, Ye B, Zhang J, Ying L, Chen Y: RDW to platelet ratio: a novel noninvasive index for predicting hepatic fibrosis and cirrhosis in chronic hepatitis B. PLoS One. 2013, 8 (7): e68780- 10.1371/journal.pone.0068780PubMed CentralView ArticlePubMedGoogle Scholar
- Kim HM, Kim BS, Cho YK, Kim BI, Sohn CI, Jeon WK, Kim HJ, Park DI, Park JH, Joo KJ, Kim CJ, Kim YS, Heo WJ, Choi WS: Elevated red cell distribution width is associated with advanced fibrosis in NAFLD. Clin Mol Hepatol. 2013, 19 (3): 258-265. 10.3350/cmh.2013.19.3.258PubMed CentralView ArticlePubMedGoogle Scholar
- Utzschneider KM, Kahn SE: Review: the role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab. 2006, 91 (12): 4753-4761. 10.1210/jc.2006-0587View ArticlePubMedGoogle Scholar
- Gruben N, Shiri-Sverdlov R, Koonen DP, Hofker MH: Nonalcoholic fatty liver disease: a main driver of insulin resistance or a dangerous liaison?. Biochim Biophys Acta. 2014, 1842 (11): 2329-2343. 10.1016/j.bbadis.2014.08.004View ArticlePubMedGoogle Scholar
- Choi CS, Savage DB, Kulkarni A, Yu XX, Liu ZX, Morino K, Kim S, Distefano A, Samuel VT, Neschen S, Zhang D, Wang A, Zhang XM, Kahn M, Cline GW, Pandey SK, Geisler JG, Bhanot S, Monia BP, Shulman GI: Suppression of diacylglycerol acyltransferase-2 (DGAT2), but not DGAT1, with antisense oligonucleotides reverses diet-induced hepatic steatosis and insulin resistance. J Biol Chem. 2007, 282 (31): 22678-22688. 10.1074/jbc.M704213200View ArticlePubMedGoogle Scholar
- Chan SM, Sun RQ, Zeng XY, Choong ZH, Wang H, Watt MJ, Ye JM: Activation of PPARα ameliorates hepatic insulin resistance and steatosis in high fructose-fed mice despite increased endoplasmic reticulum stress. Diabetes. 2013, 62 (6): 2095-2105. 10.2337/db12-1397PubMed CentralView ArticlePubMedGoogle Scholar
- Klover PJ, Mooney RA: Hepatocytes: critical for glucose homeostasis. Int J Biochem Cell Biol. 2004, 36 (5): 753-758. 10.1016/j.biocel.2003.10.002View ArticlePubMedGoogle Scholar
- Jornayvaz FR, Shulman GI: Diacylglycerol activation of protein kinase Cϵ and hepatic insulin resistance. Cell Metab. 2012, 15 (5): 574-584. 10.1016/j.cmet.2012.03.005PubMed CentralView ArticlePubMedGoogle Scholar
- Liang W: Lindeman JH2, Menke AL3, Koonen DP4, Morrison M5, Havekes LM1, van den Hoek AM5, Kleemann R6: Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1β-induced chronic inflammation. Lab Invest. 2014, 94 (5): 491-502. 10.1038/labinvest.2014.11View ArticlePubMedGoogle Scholar
- Seki E, Brenner DA, Karin M: A liver full of JNK: signaling in regulation of cell function and disease pathogenesis, and clinical approaches. Gastroenterology. 2012, 143 (2): 307-320. 10.1053/j.gastro.2012.06.004PubMed CentralView ArticlePubMedGoogle Scholar
- Baffy G: Kupffer cells in non-alcoholic fatty liver disease: the emerging view. J Hepatol. 2009, 51 (1): 212-223. 10.1016/j.jhep.2009.03.008PubMed CentralView ArticlePubMedGoogle Scholar
- Muneyuki T, Nakajima K, Aoki A, Yoshida M, Fuchigami H, Munakata H, Ishikawa SE, Sugawara H, Kawakami M, Momomura S, Kakei M: Latent associations of low serum amylase with decreased plasma insulin levels and insulin resistance in asymptomatic middle-aged adults. Cardiovasc Diabetol. 2012, 11: 80- 10.1186/1475-2840-11-80PubMed CentralView ArticlePubMedGoogle Scholar
- Nakajima K, Muneyuki T, Munakata H, Kakei M: Revisiting the cardiometabolic relevance of serum amylase. BMC Res Notes. 2011, 4: 419- 10.1186/1756-0500-4-419PubMed CentralView ArticlePubMedGoogle Scholar
- Lann D, LeRoith D: Insulin resistance as the underlying cause for the metabolic syndrome. Med Clin North Am. 2007, 91: 1063-1077. 10.1016/j.mcna.2007.06.012View ArticlePubMedGoogle Scholar
- Zhang X, Cui Y, Fang L, Li F: Chronic high-fat diets induce oxide injuries and fibrogenesis of pancreatic cells in rats. Pancreas. 2008, 37: e31-e38. 10.1097/MPA.0b013e3181744b50View ArticlePubMedGoogle Scholar
- van Geenen EJ, Smits MM, Schreuder TC, van der Peet DL, Bloemena E, Mulder CJ: Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease. Pancreas. 2010, 39 (8): 1185-1190. 10.1097/MPA.0b013e3181f6fce2View ArticlePubMedGoogle Scholar
- Sepe PS, Ohri A, Sanaka S, Berzin TM, Sekhon S, Bennett G, Mehta G, Chuttani R, Kane R, Pleskow D, Sawhney MS: A prospective evaluation of fatty pancreas by using EUS. Gastrointest Endosc. 2011, 73 (5): 987-993. 10.1016/j.gie.2011.01.015View ArticlePubMedGoogle Scholar
- Kharroubi I, Ladriere L, Cardozo AK, Dogusan Z, Cnop M, Eizirik DL: Free fatty acids and cytokines induce pancreatic beta-cell apoptosis by different mechanisms: role of nuclear factor-kappaB and endoplasmic reticulum stress. Endocrinology. 2004, 145: 5087-5096. 10.1210/en.2004-0478View ArticlePubMedGoogle Scholar
- Sumida Y, Nakajima A, Itoh Y: Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Gastroenterol. 2014, 20 (2): 475-485. 10.3748/wjg.v20.i2.475PubMed CentralView ArticlePubMedGoogle Scholar
- Demir M, Lang S, Schlattjan M, Drebber U, Wedemeyer I, Nierhoff D, Kaul I, Sowa J, Canbay A, Töx U, Steffen HM: NIKEI: a new inexpensive and non-invasive scoring system to exclude advanced fibrosis in patients with NAFLD. PLoS One. 2013, 8 (3): e58360- 10.1371/journal.pone.0058360PubMed CentralView ArticlePubMedGoogle Scholar
- Pitt HA: Hepato-pancreato-biliary fat: the good, the bad and the ugly. HPB (Oxford). 2007, 9 (2): 92-97. 10.1080/13651820701286177View ArticleGoogle Scholar
- Patel NS, Peterson MR, Brenner DA, Heba E, Sirlin C, Loomba R: Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2013, 37 (6): 630-639. 10.1111/apt.12237PubMed CentralView ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.