World J Gastroenterol. 2014 Nov 7;20(41):15351-7.

Resistin is not an appropriate biochemical marker to predict severity of acute pancreatitis: a case-controlled study.

Al-Maramhy H, Abdelrahman AI, Sawalhi S.

Hamdi Al-Maramhy, Samer Sawalhi, Department of Surgery, College of Medicine, Taibah University, Al-Madina 30001, Saudi Arabia.

 

Abstract

AIM: To assess levels of serum resistin upon hospital admission as a predictor of acute pancreatitis (AP) severity.

METHODS: AP is both a common and serious disease, with severe cases resulting in a high mortality rate. Several predictive inflammatory markers have been used clinically to assess severity. This prospective study collected data from 102 patients who were diagnosed with an initial acute biliary pancreatitis between March 2010 and February 2013. Measurements of body mass index (BMI) and waist circumference (WC) were obtained and serum resistin levels were analyzed at the time of hospital admission using enzyme-linked immunosorbent assay. Additionally, resistin levels were measured from a control group after matching gender, BMI and age.

RESULTS: A total of 102 patients (60 females and 42 males) were diagnosed with acute gallstone-induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m(2) (Obese, class I). Twenty-two patients (21.6%) had severe AP, while eighty-eight patients had mild pancreatitis (78.4%). Our results showed that BMI significantly correlated with pancreatitis severity (P = 0.007). Serum resistin did not correlate with BMI, weight or WC. Furthermore, serum resistin was significantly higher in patients with AP compared to control subjects (P < 0.0001). The mean resistin values upon admission were 17.5 ng/mL in the severe acute biliary pancreatitis group and 16.82 ng/mL in the mild AP group (P = 0.188), indicating that resistin is not an appropriate predictive marker of clinical severity.

CONCLUSION: We demonstrate that obesity is a risk factor for developing severe AP. Further, although there is a correlation between serum resistin levels and AP at the time of hospital admission, resistin does not adequately serve as a predictive marker of clinical severity.

KEYWORDS: Acute pancreatitis; Body mass index; Resistin; Waist circumference

PMID: 25386084

 

Supplement:

The prevalence of acute pancreatitis (AP) is increasing and is paralleled by an increased prevalence of obesity. Obesity is a chronic, low-grade inflammatory state characterized by high circulating levels of proinflammatory cytokines [1], and associated with higher levels of inflammatory markers[2], which could potentially be of predictive value. A large amount of visceral fat surrounding the pancreas may easily promote the inflammation in AP[3].

Central fat distribution was revealed as a more definitive risk factor than the actual amount of fat and it is, therefore, plausible that the inflammatory properties of intrapancreatic fat may be involved in triggering the onset of AP. In line with these data, obesity may intensify the immune response, which is able to exacerbate pancreatic injury.

High levels of adipocytokines, including resistin , can indicate a large amount of visceral fat surrounding the pancreas.

Resistin has been identified in pancreatic islets. Recently, resistin was shown to serve as a marker of monocyte activation[4]. Thus, resistin can be used for detection of early inflammation of peripancreatic adipose tissue infiltrated by monocytes. Importantly, human resistin mRNA expression is higher in abdominal adipose tissue than in subcutaneous adipose tissue [5], therefore we chose to investigate the serum level of resistin in AP patients to assess its potential value for detecting pancreatitis severity specifically induced by adipose tissue inflammation. Until now, resistin has not been reported in purely acute biliary pancreatitis patients of a substantial sample size.

Our aim is to study the ability of serum resistin to predict the clinical severity of acute biliary pancreatitis and its potential use as a marker of pancreatic injury.

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Table 1

 

Methods:

Venous blood samples were collected and, after sampling, the tubes were immediately centrifuged at 1.5g for 10minutes. Aliquots of serum were stored at −20°C and routine

haematology and biochemistry tests were performed. All biochemical measurements were carried out by the same team of laboratory technicians and samples were collected after the patient’s first attack of AP at the time of hospital admission.

We enrolled a control group of 102 persons with matched BMI, gender and age,Figure[1], because serum resistin concentration increases in obesity, and is positively correlated with BMI, insulin resistance or body fat[6]. Resistin plasma samples for both test patients and control groups were stored at -80 ℃ and diluted 100-fold and stored until biochemical analysis was completed. as recommended by the manufacturer (Assaypro, Saint Charles, MO, USA)

One technician performed the analysis in a blinded fashion. Resistin concentrations for both groups were measured by using enzyme-linked immunosorbent assay (ELISA) [Figure 2]

 

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Figure 1

 

assay conditions.

The serum was quantitatively assayed for resistin using a sandwich enzyme immunoassay. Standards and samples were sandwiched by immobilized antibodies and biotinylated polyclonal antibodies specific for resistin . Samples were analyzed using the Bio-plex suspension array system (Bio-Rad Laboratories Inc., Hercules, CA, USA)-Figure2 , which included a fluorescent reader, and Bio-plex Manager analytic software version 6.1.1 (Bio-Rad Laboratories Inc.,Hercules, CA, USA) at the Taibah University Biochemical Department. The mean value for duplicate readings was calculated for each standard and sample. The cut-off value of resistin was 15 ng/mL.

 

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Figure 2

 

Results

Our study consisted of 102 patients (60 females and 42 males) diagnosed with an initial first attack of acute gallstone- induced pancreatitis. The mean age was 45 years, and mean BMI value was 30.5 kg/m2 (Obese, class Ⅰ). Patient characteristics are summarized in Table 1. None of the patients had ever consumed alcohol or had a history of drug consumption.

We investigated the relationship between severity of pancreatitis and risk factors such as age, gender, BMI, WC, and body weight. Our results showed that only BMI significantly correlated with severity of acute biliary pancreatitis (P = 0.007; Figure 3). Serum resistin concentration was significantly higher in patients with AP compared with control subjects (Figures 4).

Resistin concentrations upon admission correlated with AP. Receiver-operator curve and area under the curve (AUC) delineate sensitivity and specificity of serum resistin concentration as an inflammatory marker on the day of admission in AP, AUC> 97% and cutoff value: 15 ng/mL (Figures 5 A and B), but resistin failed to serve as a predictive marker of clinical severity in AP (P = 0.188; Figure 6).

 

 

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Figure3: The significant correlation between BMI and severity of biliary pancreatitis (mild/severe) (P=0.007)

 

 

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Figure 4 :Significant difference between resistin level in acute biliary pancreatitis patients and control subjects (P = 0.0001).

 

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Figure 5 (A-B)

 

 

The importance of this study is :

Many inflammatory markers, such as trypsinogen activation peptide, interleukin-6, interleukin-10, procalcitonin, phospholipase A2 and C-reactive protein, have been used to assess the severity of pancreatitis. [7] . In our study, we used a biochemical marker that specifically reflects the inflammation of peri-pancreatic adipose tissue. In addition, our study was designed with strict exclusion criteria to eliminate any confounding variables that affected patients’ weight or BMI.

Our study, however, had twice the sample size and most of the pancreatitis cases were biliary in origin, which has not previously been extensively studied. Additionally, we measured the serum resistin levels in our patients within a few hours after a confirmed diagnosis of acute biliary pancreatitis upon hospital admission.

Exploration of an inflammatory marker, such as resistin, reflects the severity burden of AP and is superior over other scoring approaches. Before resistin can be used widely in the clinical setting, our results must be confirmed by larger and multi-center studies.

Resistin serum levels can be used as a diagnostic marker for acute pancreatitis , as levels are increased upon hospital admission.

The use of new biochemical marker in a cute gallstone induced pancreatitis appears very promising.

 

 

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Figure-6

 

References

1-Lee YH, Pratley RE. The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep 2005; 5:70–5. http://dx.doi.org/10.1007/s11892-005-0071-7

2-Sempere L, Martinez J, de Madaria E, et al. Obesity and fat distribution imply a greater systemic inflammatory response and a worse prognosis in acute pancreatitis. Pancreatology 2008; 8:257–64. http://dx.doi.org/10.1159/000134273

3-Yashima Y, Isayama H, Tsujino T, et al. A large volume of visceral adipose tissue leads to severe acute pancreatitis. J Gastroenterol 2011; 46:1213–8. http://dx.doi.org/10.1007/s00535-011-0430-x

4-Schäffler A, Hamer O, Dickopf J, Goetz A, Landfried K, Voelk M, Herfarth H, Kopp A, Büchler C, Schölmerich J, Brünnler T. Admission resistin levels predict peripancreatic necrosis and clinical severity in acute pancreatitis. Am J Gastroenterol 2010; 105: 2474-2484 [PMID: 20648005 DOI: 10.1038/ajg.2010.278]

5-McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, Crocker J, Barnett AH, Kumar S. Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 2002; 87: 2407 [PMID: 11994397 DOI: 10.1210/jcem.87.5.8627]

6-Fujinami A, Obayashi H, Ohta K, Ichimura T, Nishimura M, Matsui H, Kawahara Y, Yamazaki M, Ogata M, Hasegawa G, Nakamura N, Yoshikawa T, Nakano K, Ohta M. Enzymelinked immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes. Clin Chim Acta 2004; 339: 57-63 [PMID: 14687894 DOI: 10.1016/j.cccn.2003.09.009]

7-Manes G, Spada OA, Rabitti PG, Pacelli L, Iannaccone L, Uomo G. Serum interleukin-6 in acute pancreatitis due to common bile duct stones. A reliable marker of necrosis. Recenti Prog Med 1997; 88: 69-72 [PMID: 9148369

 

Acknowledgements:  This study was supported by research grant no 433/780 from Scientific Research Deanship,Taibah University

 

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Contact

Samer Al-Sawalhi

Assistant Professor and surgical consultant

Department of Surgery-Taibah University

E-mail(skyscraper555@yahoo.com)

Tel:+962776103548

 

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