Mayo Clinic Proceedings Home

Glucose Control, Diabetes Status, and Mortality in Critically Ill Patients

The Continuum From Intensive Care Unit Admission to Hospital Discharge



      To describe the relationships among glycemic control, diabetes mellitus (DM) status, and mortality in critically ill patients from intensive care unit (ICU) admission to hospital discharge.

      Patients and Methods

      This is a retrospective investigation of 6387 ICU patients with 5 or more blood glucose (BG) tests and 4462 ICU survivors admitted to 2 academic medical centers from July 1, 2010, through December 31, 2014. We studied the relationships among mean BG level, hypoglycemia (BG level <70 mg/dL [to convert to mmol/L, multiply by 0.0555]), high glucose variability (coefficient of variation ≥20%), DM status, and mortality.


      The ICU mortality for patients without DM with ICU mean BG levels of 80 to less than 110, 110 to less than 140, 140 to less than 180, and at least 180 mg/dL was 4.50%, 7.30%, 12.16%, and 32.82%, respectively. Floor mortality for patients without DM with these BG ranges was 2.74%, 2.64%, 7.88%, and 5.66%, respectively. The ICU and floor mean BG levels of 80 to less than 110 and 110 to less than 140 mg/dL were independently associated with reduced ICU and floor mortality compared with mean BG levels of 140 to less than 180 mg/dL in patients without DM (odds ratio [OR] [95% CI]: 0.43 (0.28-0.66), 0.62 (0.45-0.85), 0.41 (0.23-0.75), and 0.40 (0.25-0.63), respectively) but not in patients with DM. Both ICU and floor hypoglycemia and increased glucose variability were strongly associated with ICU and floor mortality in patients without DM, and less so in those with DM. The independent association of dysglycemia occurring in either setting with mortality was cumulative in patients without DM.


      These findings support the importance of glucose control across the entire trajectory of hospitalization in critically ill patients and suggest that the BG target of 140 to less than 180 mg/dL is not appropriate for patients without DM. The optimal BG target for patients with DM remains uncertain.

      Abbreviations and Acronyms:

      APACHE (Acute Physiology and Chronic Health Evaluation), BG (blood glucose), DM (diabetes mellitus), CV (coefficient of variation), HbA1c (hemoglobin A1c), ICU (intensive care unit), LOS (length of stay), OR (odds ratio), PM (predicted mortality)
      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 Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Krinsley J.S.
        Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients.
        Mayo Clin Proc. 2003; 78: 1471-1478
        • Falciglia M.
        • Freyberg R.W.
        • Almenoff P.L.
        • D'alessio D.A.
        • Render M.L.
        Hyperglycemia-related mortality in critically ill patients varies with admission diagnosis.
        Crit Care Med. 2009; 37: 3001-3009
        • Krinsley J.S.
        • Grover A.
        Severe hypoglycemia in critically ill patients: risk factors and outcomes.
        Crit Care Med. 2007; 35: 2262-2267
        • Egi M.
        • Bellomo R.
        • Stachowski E.
        • et al.
        Hypoglycemia and outcome in critically ill patients.
        Mayo Clin Proc. 2010; 85: 217-224
        • Krinsley J.S.
        • Schultz M.J.
        • Spronk P.E.
        • et al.
        Mild hypoglycemia is independently associated with increased mortality in the critically ill.
        Crit Care. 2011; 15: R173
        • Egi M.
        • Bellomo R.
        • Stachowski E.
        • French C.J.
        • Hart G.
        Variability of blood glucose concentration and short-term mortality in critically ill patients.
        Anesthesiology. 2006; 105: 244-252
        • Krinsley J.S.
        Glycemic variability: a strong independent predictor of mortality in critically ill patients.
        Crit Care Med. 2008; 36: 3008-3013
        • Krinsley J.S.
        Glycemic control, diabetic status, and mortality in a heterogeneous population of critically ill patients before and during the era of intensive glycemic management: six and one-half years experience at a university-affiliated community hospital.
        Semin Thorac Cardiovasc Surg. 2006; 18: 317-325
        • Egi M.
        • Bellomo R.
        • Stachowski E.
        • et al.
        Blood glucose concentration and outcome of critical illness: the impact of diabetes.
        Crit Care Med. 2008; 36: 2249-2255
        • Siegelaar S.E.
        • Hickmann M.
        • Hoekstra J.B.
        • Holleman F.
        • DeVries J.H.
        The effect of diabetes on mortality in critically ill patients: a systematic review and meta-analysis.
        Crit Care. 2011; 15: R205
        • Krinsley J.S.
        • Egi M.
        • Kiss A.
        • et al.
        Diabetic status and the relation of the three domains of glycemic control to mortality in critically ill patients: an international multicenter cohort study.
        Crit Care. 2013; 17: R37
        • Sechterberger M.K.
        • Bosman R.J.
        • Oudemans-van Straaten H.M.
        • et al.
        The effect of diabetes mellitus on the association between measures of glycaemic control and ICU mortality: a retrospective cohort study.
        Crit Care. 2013; 17: R52
        • Lanspa M.J.
        • Hirshberg E.L.
        • Phillips G.D.
        • Holmen J.
        • Stoddard G.
        • Orme J.
        Moderate glucose control is associated with increased mortality compared with tight glucose control in critically ill patients without diabetes.
        Chest. 2013; 143: 1226-1234
        • Krinsley J.S.
        • Preiser J.C.
        • Hirsch I.B.
        Safety and efficacy of personalized glycemic control in critically ill patients: a 2 year before and after interventional trial.
        Endocr Pract. 2017; 23: 318-330
        • Umpierrez G.E.
        • Kosiborod M.
        Inpatient dysglycemia and clinical outcomes: association or causation?.
        J Diabetes Complications. 2014; 28: 427
        • Furnary A.P.
        • Wu Y.
        • Bookin S.O.
        Effect of hyperglycemia and continuous intravenous insulin infusions on outcomes of cardiac surgical procedures: the Portland Diabetic Project.
        Endocr Pract. 2004; 10: 21-33
        • Greco G.
        • Ferket B.S.
        • D'Alessandro D.A.
        • et al.
        Diabetes and the association of postoperative hyperglycemia with clinical and economic outcomes in cardiac surgery.
        Diabetes Care. 2016; 39: 408-417
        • McAlister F.A.
        • Majumdar S.R.
        • Blitz S.
        • Rowe B.H.
        • Romney J.
        • Marrie T.J.
        The relation between hyperglycemia and outcomes in 2,471 patients admitted to the hospital with community-acquired pneumonia.
        Diabetes Care. 2005; 28: 810-815
        • Baker E.H.
        • Janaway C.H.
        • Philips B.J.
        • et al.
        Hyperglycaemia is associated with poor outcomes in patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease.
        Thorax. 2006; 61: 284-289
        • Turchin A.
        • Matheny M.E.
        • Shubina M.
        • Scanlon J.V.
        • Greenwood B.
        • Pendergrass M.L.
        Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward.
        Diabetes Care. 2009; 32: 1153-1157
        • Zapatero A.
        • Gómez-Huelgas R.
        • González N.
        • et al.
        Frequency of hypoglycemia and its impact on length of stay, mortality, and short-term readmission in patients with diabetes hospitalized in internal medicine wards.
        Endocr Pract. 2014; 20: 870-875
        • Brodovicz K.G.
        • Mehta V.
        • Zhang Q.
        • et al.
        Association between hypoglycemia and inpatient mortality and length of hospital stay in hospitalized, insulin-treated patients.
        Curr Med Res Opin. 2013; 29: 101-107
        • Mendez C.E.
        • Mok K.T.
        • Ata A.
        • Tanenberg R.J.
        • Calles-Escandon J.
        • Umpierrez G.E.
        Increased glycemic variability is independently associated with length of stay and mortality in noncritically ill hospitalized patients.
        Diabetes Care. 2013; 36: 4091-4097
        • Dungan K.M.
        • Binkley P.
        • Nagaraja H.N.
        • Schuster D.
        • Osei K.
        The effect of glycaemic control and glycaemic variability on mortality in patients hospitalized with congestive heart failure.
        Diabetes Metab Res Rev. 2011; 27: 85-93
        • Farrokhi F.
        • Chandra P.
        • Smiley D.
        • et al.
        Glucose variability is an independent predictor of mortality in hospitalized patients treated with total parenteral nutrition.
        Endocr Pract. 2013; 20: 41-45
        • Bersoux S.
        • Cook C.B.
        • Kongable G.L.
        • Shu J.
        Retrospective study of glycemic control following transition from the intensive care unit in a national sample of US hospitals.
        Endocr Pract. 2015; 21: 986-992
        • Zimmerman J.E.
        • Kramer A.A.
        • McNair D.S.
        • Malila F.M.
        Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients.
        Crit Care Med. 2006; 34: 1297-1310
        • Meyfroidt G.
        • Keenan D.M.
        • Wang X.
        • Wouters P.J.
        • Veldhuis J.D.
        • Van den Berghe G.
        Dynamic characteristics of blood glucose time series during the course of critical illness: effects of intensive insulin therapy and relative association with mortality.
        Crit Care Med. 2010; 38: 1021-1029
        • NICE-SUGAR Study Investigators
        Hypoglycemia and risk of death in critically ill patients.
        N Engl J Med. 2012; 2012: 1108-1118
        • Moghissi E.S.
        • Korytkowski M.T.
        • DiNardo M.
        • et al.
        American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control.
        Diabetes Care. 2009; 32: 1119-1131
        • Ichai C.
        • Preiser J.C.
        International recommendations for glucose control in adult non diabetic critically ill patients.
        Crit Care. 2010; 14: R166
        • NICE-SUGAR Study Investigators
        Intensive versus conventional glucose control in critically ill patients.
        N Engl J Med. 2009; 2009: 1283-1297
        • Egi M.
        • Bellomo R.
        • Stachowski E.
        • et al.
        The interaction of chronic and acute glycemia with mortality in critically ill patients with diabetes.
        Crit Care Med. 2011; 39: 105-111
        • Plummer M.P.
        • Bellomo R.
        • Cousins C.E.
        • et al.
        Dysglycaemia in the critically ill and the interaction of chronic and acute glycaemia with mortality.
        Intensive Care Med. 2014; 40: 973-980
        • Egi M.
        • Krinsley J.S.
        • Maurer P.
        • et al.
        Pre-morbid glycemic control modifies the interaction between acute hypoglycemia and mortality.
        Intensive Care Med. 2016; 42: 562-571

      Linked Article

      • Correction
        Mayo Clinic ProceedingsVol. 94Issue 6
        • Preview
          In the article by Krinsley et al entitled “Glucose Control, Diabetes Status, and Mortality in Critically Ill Patients,” published in the July 2017 issue of Mayo Clinic Proceedings (Mayo Clin Proc. 2017;92(7):1019-1029), the ages listed in Table 2 for Patients with diabetes, Survivors and Non-survivors were incorrect. The correct data are: Survivors 68 (59-77), Non-survivors 75 (67-83), P=0.0001.
        • Full-Text
        • PDF