Liver, Pancreas and Biliary Tract| Volume 53, ISSUE 4, P445-451, April 2021

Uncontrolled diabetes mellitus increases risk of infection in patients with advanced cirrhosis

Published:November 02, 2020DOI:



      Diabetes mellitus (DM) is common in patients with cirrhosis and is associated with increased risk of infection.


      To analyze the impact of uncontrolled DM on infection and mortality among inpatients with advanced cirrhosis.


      This study utilized the Nationwide Inpatient Sample from 1998 to 2014. We defined advanced cirrhosis using a validated ICD-9-CM algorithm requiring a diagnosis of cirrhosis and clinically significant portal hypertension or decompensation. The primary outcome was bacterial infection. Secondary outcomes included inpatient mortality stratified by elderly age (age≥70). Multivariable logistic regression analyzed outcomes.


      906,559 (29.2%) patients had DM and 109,694 (12.1%) were uncontrolled. Patients who had uncontrolled DM were younger, had less ascites, but more encephalopathy. Bacterial infection prevalence was more common in uncontrolled DM (34.2% vs. 28.4%, OR 1.33, 95% CI 1.29–1.37, p<0.001). Although uncontrolled DM was not associated with mortality, when stratified by age, elderly patients with uncontrolled DM had a significantly higher risk of inpatient mortality (OR 1.62, 95% CI 1.46–1.81).


      Uncontrolled DM is associated with increased risk of infection, and when combined with elderly age is associated with increased risk of inpatient mortality. Glycemic control is a modifiable target to improve morbidity and mortality in patients with advanced cirrhosis.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Digestive and Liver Disease
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Menke A.
        • Casagrande S.
        • Geiss L.
        • Cowie C.C.
        Prevalence of and trends in diabetes among adults in the United States, 1988-2012.
        J Am Med Assoc. 2015;
        • Scaglione S.
        • Kliethermes S.
        • Cao G.
        • Shoham D.
        • Durazo R.
        • Luke A.
        • et al.
        The epidemiology of cirrhosis in the United States a population-based study.
        J Clin Gastroenterol. 2015; 49: 690-696
        • Davila J.A.
        • Morgan R.O.
        • Shaib Y.
        • McGlynn K.A.
        • El-Serag H.B.
        Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study.
        Gut. 2005; 54: 533-539
        • Wang P.
        • Kang D.
        • Cao W.
        • Wang Y.
        • Liu Z.
        Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis.
        Diabetes Metab Res Rev. 2012;
        • Noureddin M.
        • Vipani A.
        • Bresee C.
        • Todo T.
        • Kim I.K.
        • Alkhouri N.
        • et al.
        NASH leading cause of liver transplant in women: updated analysis of indications for liver transplant and ethnic and gender variances.
        Am J Gastroenterol. 2018;
        • Leone S.
        • Lorenzini P.
        • Cozzi-Lepri A.
        • Orofino G.
        • Bernacchia D.
        • Castagna A.
        • et al.
        Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study.
        Eur J Clin Microbiol Infect Dis. 2019;
        • Elkrief L.
        • Chouinard P.
        • Bendersky N.
        • Hajage D.
        • Larroque B.
        • Babany G.
        • et al.
        Diabetes mellitus is an independent prognostic factor for major liver-related outcomes in patients with cirrhosis and chronic hepatitis C.
        Hepatology. 2014;
        • Kothari A.N.
        • Loy V.M.
        • Brownlee S.A.
        • Ezure Y.
        • Schaidle-Blackburn C.
        • Cotler S.J.
        • et al.
        Adverse effect of post-discharge care fragmentation on outcomes after readmissions after liver transplantation.
        J Am Coll Surg. 2017; 225: 62-67
        • Jacquez-Quintana J.O.
        • Garcia-Compean D.
        • Gonzalez-Gonzalez J.A.
        • Villarreal-Pérez J.Z.
        • Lavalle-González F.J.
        • Munoz-Espinoza L.
        • et al.
        The impact of diabetes mellitus in mortality of patients with compensated liver cirrhosis-a prospective study.
        Ann Hepatol. 2011; 10: 56-62
        • Pearson-Stuttard J.
        • Blundell S.
        • Harris T.
        • Cook D.G.
        • Critchley J.
        Diabetes and infection: assessing the association with glycaemic control in population-based studies.
        Lancet Diabetes Endocrinol. 2016;
        • Diaz J.
        • Monge E.
        • Roman R.
        • Ulloa V.
        Diabetes as a risk factor for infections in cirrhosis.
        Am J Gastroenterol. 2008; 103: 248
        • Hine J.L.
        • de Lusignan S.
        • Burleigh D.
        • Pathirannehelage S.
        • McGovern A.
        • Gatenby P.
        • et al.
        Association between glycaemic control and common infections in people with type 2 diabetes: a cohort study.
        Diabet Med. 2017;
        • Muller L.M.A.J.
        • Gorter K.J.
        • Hak E.
        • Goudzwaard W.L.
        • Schellevis F.G.
        • Hoepelman A.I.M.
        • et al.
        Increased risk of common infections in patients with type 1 and type 2 diabetes mellitus.
        Clin Infect Dis. 2005;
        • Han H.
        • Sun Y.
        • Zhang Y.
        • Tacke F.
        • haitao Zhao
        • Deng H.
        • et al.
        Prevalence and in-hospital outcomes of diabetes mellitus in elderly patients with liver cirrhosis.
        AME Med J. 2017; 2
        • Bajaj J.S.
        • O'Leary J.G.
        • Reddy K.R.
        • Wong F.
        • Biggins S.W.
        • Patton H.
        • et al.
        Survival in infection-related acute-on-chronic liver failure is defined by extrahepatic organ failures.
        Hepatology. 2014; 60: 250-256
        • O'Leary J.G.
        • Reddy K.R.
        • Garcia-Tsao G.
        • Biggins S.W.
        • Wong F.
        • Fallon M.B.
        • et al.
        NACSELD acute-on-chronic liver failure (NACSELD-ACLF) score predicts 30-day survival in hospitalized patients with cirrhosis.
        Hepatology. 2018; 67: 2367-2374
        • Bajaj J.S.
        • O'Leary J.G.
        • Reddy K.R.
        • Wong F.
        • Olson J.C.
        • Subramanian R.M.
        • et al.
        Second infections independently increase mortality in hospitalized patients With cirrhosis: the north American Consortium for the study of end-stage liver disease (NACSELD) experience.
        Hepatology. 2012; 56: 2328-2335
      1. Nationwide Inpatient Sample (NIS), Healthcare cost and utilization project, Agency for Healthcare Research and Quality 1998–2014.

        • Goldberg D.
        • Lewis J.D.
        • Halpern S.D.
        • Weiner M.
        • Lo Re V.
        Validation of three coding algorithms to identify patients with end-stage liver disease in an administrative database.
        Pharmacoepidemiol Drug Saf. 2012; 21: 765-769
        • Khokhar B.
        • Jette N.
        • Metcalfe A.
        • Cunningham C.T.
        • Quan H.
        • Kaplan G.G.
        • et al.
        Systematic review of validated case definitions for diabetes in ICD-9-coded and ICD-10-coded data in adult populations.
        BMJ Open. 2016;
        • Chen G.
        • Khan N.
        • Walker R.
        • Quan H.
        Validating ICD coding algorithms for diabetes mellitus from administrative data.
        Diabetes Res Clin Pract. 2010;
        • Goto T.
        • Yoshida K.
        • Tsugawa Y.
        • Filbin M.R.
        • Camargo C.A.
        • Hasegawa K.
        Mortality trends in U.S. adults with septic shock, 2005-2011: a serial cross-sectional analysis of nationally-representative data.
        BMC Infect Dis. 2016; 16
        • Nanchal R.
        • Kumar G.
        • Taneja A.
        • Patel J.
        • Deshmukh A.
        • Tarima S.
        • et al.
        Pulmonary embolism: the weekend effect.
        Chest. 2012;
        • Waikar S.S.
        Validity of international classification of diseases, ninth revision, clinical modification codes for acute renal failure.
        J Am Soc Nephrol. 2006;
        • Rosenblatt R.E.
        • Shen N.
        • Tafesh Z.H.
        • Cohen-Mekelburg S.
        • Crawford C.V.
        • Kumar S.
        • et al.
        The NACSELD‐ACLF score accurately predicts survival: an external validation using a national cohort.
        Liver Transpl. 2019;
        • Rosenblatt R.
        • Mehta A.
        • Cohen-Mekelburg S.
        • Shen N.
        • Snell D.
        • Lucero C.
        • et al.
        The rise of clostridioides difficile infections and fall of associated mortality in hospitalized advanced cirrhotics.
        Liver Int. 2019; 39: 1263-1270
        • Tapper E.B.
        • Halbert B.
        • Mellinger J.
        Rates of and reasons for hospital readmissions in patients with cirrhosis: a multistate population-based cohort study.
        Clin Gastroenterol Hepatol. 2016; 14 (e2): 1181-1188
        • Mellinger J.L.
        • Richardson C.R.
        • Mathur A.K.
        • Volk M.L.
        Variation among United States hospitals in inpatient mortality for cirrhosis.
        Clin Gastroenterol Hepatol. 2015; 13: 577-584
        • Drahos J.
        • Vanwormer J.J.
        • Greenlee R.T.
        • Landgren O.
        • Koshiol J.
        Accuracy of ICD-9-CM codes in identifying infections of pneumonia and herpes simplex virus in administrative data.
        Ann Epidemiol. 2013;
        • Zhan C.
        • Elixhauser A.
        • Richards C.L.
        • Wang Y.
        • Baine W.B.
        • Pineau M.
        • et al.
        Identification of hospital-acquired catheter-associated urinary tract infections from medicare claims: sensitivity and positive predictive value.
        Med Care. 2009;
        • Levine P.J.
        • Elman M.R.
        • Kullar R.
        • Townes J.M.
        • Bearden D.T.
        • Vilches-Tran R.
        • et al.
        Use of electronic health record data to identify skin and soft tissue infections in primary care settings: a validation study.
        BMC Infect Dis. 2013;
        • Elixhauser A.
        • Steiner C.
        • Harris D.R.
        • Coffey R.M.
        Comorbidity measures for use with administrative data.
        Med Care. 1998; 36: 8-27
        • de Vries F.E.E.
        • Gans S.L.
        • Solomkin J.S.
        • Allegranzi B.
        • Egger M.
        • Dellinger E.P.
        • et al.
        Meta-analysis of lower perioperative blood glucose target levels for reduction of surgical-site infection.
        Br J Surg. 2017;
        • Berriós-Torres S.I.
        • Umscheid C.A.
        • Bratzler D.W.
        • Leas B.
        • Stone E.C.
        • Kelz R.R.
        • et al.
        Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017.
        JAMA Surg. 2017;
        • Khan R.
        • Foster G.
        • Chowdhury T.
        Managing diabetes in patients with chronic liver disease.
        Postgrad Med. Jul 2012; 124: 130-137
        • Tolman K.G.
        • Fonseca V.
        • Dalpiaz A.
        • Tan M.H.
        Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease.
        Diabetes Care. 2007;
        • Nadelson J.
        • Satapathy S.K.
        • Nair S.
        Glycated hemoglobin levels in patients with decompensated cirrhosis.
        Int J Endocrinol. 2016;
        • Stratton I.M.
        Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.
        BMJ. 2000; 321: 405-412
        • Arvaniti V.
        • D'Amico G.
        • Fede G.
        • Manousou P.
        • Tsochatzis E.
        • Pleguezuelo M.
        • et al.
        Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis.
        Gastroenterology. 2010;
        • Montalvo-Gordon I.
        • Chi-Cervera L.A.
        • García-Tsao G.
        Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) ameliorate ascites and peripheral edema in patients with cirrhosis and diabetes.
        Hepatology. 2020;
        • Bustamante J.
        • Rimola A.
        • Ventura P.J.
        • Navasa M.
        • Cirera I.
        • Reggiardo V.
        • et al.
        Prognostic significance of hepatic encephalopathy in patients with cirrhosis.
        J Hepatol. 1999;
        • Tergast T.
        • Laser H.
        • Gerbel S.
        • Manns M.P.
        • Cornberg M.
        • Maasoumy B.
        Association between type 2 diabetes mellitus, HbA1c and the risk for spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis and ascites.
        Clin Transl Gastroenterol. 2018; 9: 189
        • Johnson E.L.
        • Feldman H.
        • Butts A.
        • Billy C.D.R.
        • Dugan J.
        • Leal S.
        • et al.
        Standards of medical care in diabetes—2019 abridged for primary care providers.
        Clin Diabetes. 2019;
        • Runyon B.A.
        Patients with deficient ascitic fluid opsonic activity are predisposed to spontaneous bacterial peritonitis.
        Hepatology. 1988;
        • Mauriello C.T.
        • Hair P.S.
        • Rohn R.D.
        • Rister N.S.
        • Krishna N.K.
        • Cunnion K.M.
        Hyperglycemia inhibits complement-mediated immunological control of S. aureus in a rat model of peritonitis.
        J Diabetes Res. 2014;
        • Runyon B.A.
        AASLD practice guideline management of adult patients with ascites due to cirrhosis: update 2012.
        Hepatology. 2013; 57: 1651-1653
        • Shakov R.
        • Salazar R.S.
        • Kagunye S.K.
        • Baddoura W.J.
        • DeBari V.A.
        Diabetes mellitus as a risk factor for recurrence of Clostridium difficile infection in the acute care hospital setting.
        Am J Infect Control. 2011;
        • Dial S.
        • Alrasadi K.
        • Manoukin C.
        • Huang A.
        • Menzies D.
        Risk of Clostridium difficile diaarhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies.
        CMAJ. 2004;
        • Stone M.A.
        • Camosso-Stefinovic J.
        • Wilkinson J.
        • De Lusignan S.
        • Hattersley A.T.
        • Khunti K.
        Incorrect and incomplete coding and classification of diabetes: a systematic review.
        Diabet Med. 2010;
        • Peng M.
        • Southern D.A.
        • Williamson T.
        • Quan H.
        Under-coding of secondary conditions in coded hospital health data: impact of co-existing conditions, death status and number of codes in a record.
        Health Inform J. 2017;
        • Kanwal F.
        • Tansel A.
        • Kramer J.
        • Feng H.
        • Asch S.
        • El-Serag H.B.
        Trends in 30-day and 1-year mortality among patients hospitalized with cirrhosis from 2004 to 2013.
        Am J Gastroenterolerican J Gastroenterol. 2017; 112: 1287-1297

      Linked Article

      • Uncontrolled diabetes mellitus and advanced cirrhosis
        Digestive and Liver DiseaseVol. 53Issue 6
        • Preview
          Rosenblatt and colleagues recently published an attractive research paper on uncontrolled diabetes mellitus (DM) and the risk of infection in patients with advanced cirrhosis [1]. In this study, the authors found that uncontrolled DM was associated with an increased risk of infection, after controlling for potential confounders. In addition, the combination of uncontrolled DM and elderly age could significantly improve the predictive value of mortality in cirrhosis patients. There is no doubt that the findings of this study will help clinicians pay more attention to the glycemic control of cirrhosis patients, so as to better refine the risk classification.
        • Full-Text
        • PDF
      • Reply to “Uncontrolled diabetes mellitus and advanced cirrhosis”
        Digestive and Liver DiseaseVol. 53Issue 6
        • Preview
          We appreciate the thoughtful letter from Dr. Zong [1]. While the use of large databases brings significant advantages, there are noteworthy limitations. The most prominent advantage is certainly the enormous power and sample size. Equally important, the Nationwide Inpatient Sample [2], the database utilized in our analysis, provides a nationally representative cohort by sampling hospitals and patients across the United States. However, as discussed in our limitations section [3], we relied on diagnosis codes for the definition of controlled and uncontrolled diabetes.
        • Full-Text
        • PDF