The interaction of chronic and acute glycemia with mortality in critically ill patients with diabetes*

Objectives:The relationship between hyperglycemia and mortality is altered by the presence of diabetes mellitus. Biological adjustment to preexisting hyperglycemia might explain this phenomenon. We tested whether the degree of preexisting hyperglycemia would modulate the association between glycemia and outcome during critical illness in patients with diabetes mellitus. Design:Retrospective observational study. Setting:Two tertiary intensive care units. Patients:Four hundred fifteen critically ill diabetic patients with HbA1c levels measured within 3 months of intensive care unit admission. Interventions:None. Measurements and Main Results:There were 9,946 blood glucose measurements in this study cohort (glucose measured 6.7 times per day; every 3.6 hrs on average). The median preadmission HbA1c level was 7.0%. There was no significant difference in HbA1c levels (p = .17) or time-weighted average of blood glucose concentrations (p = .49) between survivors and nonsurvivors. The time-weighted average of blood glucose concentrations during intensive care unit stay for nonsurvivors was lower than that of survivors when the HbA1c was >6.8%. In multivariate analysis, we found that there was a significant interaction between HbA1c and the time-weighted glucose level, indicating that the relationship between HbA1c and mortality changed according to the levels of time-weighted average of blood glucose concentrations (p = .008). As a consequence, in patients with higher (>7%) preadmission levels of HbA1c, the higher the time-weighted acute glucose concentration during intensive care unit stay (>10 mmol/L), the lower the hospital mortality compared with the lower HbA1c cohort (<7%). Conclusions:In patients with diabetes mellitus admitted to intensive care units, there was a significant interaction between preexisting hyperglycemia and the association between acute glycemia and mortality. These observations generate the hypothesis that glucose levels that are considered safe and desirable in other patients might be undesirable in diabetic patients with chronic hyperglycemia. Further studies are required to confirm or refute our findings.

[1]  S. Kaplan,et al.  Comorbidity Affects the Relationship Between Glycemic Control and Cardiovascular Outcomes in Diabetes , 2009, Annals of Internal Medicine.

[2]  Mercedes Falciglia,et al.  Hyperglycemia–related mortality in critically ill patients varies with admission diagnosis* , 2009, Critical care medicine.

[3]  Stephane Heritier,et al.  Intensive versus conventional glucose control in critically ill patients. , 2009, The New England journal of medicine.

[4]  J. Fraser,et al.  The relationship between blood glucose level and QTc duration in the critically ill. , 2009, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[5]  Michael Bailey,et al.  Blood glucose concentration and outcome of critical illness: The impact of diabetes* , 2008, Critical care medicine.

[6]  Diederick Grobbee,et al.  Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. , 2008, The New England journal of medicine.

[7]  D. Cooper,et al.  The Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. , 2008, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[8]  F. Schlenk,et al.  Insulin-related decrease in cerebral glucose despite normoglycemia in aneurysmal subarachnoid hemorrhage , 2008, Critical care.

[9]  R. Bellomo,et al.  Circadian rhythm of blood glucose values in critically ill patients , 2007, Critical care medicine.

[10]  R. Bellomo,et al.  A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients. , 2006, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[11]  J. Krinsley 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. , 2006, Seminars in thoracic and cardiovascular surgery.

[12]  N. Orford Intensive insulin therapy in septic shock. , 2006, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[13]  Rinaldo Bellomo,et al.  Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients , 2006, Anesthesiology.

[14]  R. Kalyani,et al.  Assessing glycemia in diabetes using self-monitoring blood glucose and hemoglobin A1c. , 2006, JAMA.

[15]  R. Bellomo,et al.  Intensive insulin therapy in postoperative intensive care unit patients: a decision analysis. , 2006, American journal of respiratory and critical care medicine.

[16]  G. Van den Berghe,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[17]  Brian W Whitcomb,et al.  Impact of admission hyperglycemia on hospital mortality in various intensive care unit populations* , 2005, Critical care medicine.

[18]  Daniel J. Johnson,et al.  Influence of individual characteristics on outcome of glycemic control in intensive care unit patients with or without diabetes mellitus. , 2005, Mayo Clinic proceedings.

[19]  A. May,et al.  The impact of a normoglycemic management protocol on clinical outcomes in the trauma intensive care unit. , 2005, JPEN. Journal of parenteral and enteral nutrition.

[20]  James Stephen Krinsley,et al.  Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. , 2004, Mayo Clinic proceedings.

[21]  M. Mlynarek,et al.  An Insulin Infusion Protocol in Critically Ill Cardiothoracic Surgery Patients , 2004, The Annals of pharmacotherapy.

[22]  P. Stow,et al.  Safety and feasibility of an insulin adjustment protocol to maintain blood glucose concentrations within a narrow range in critically ill patients in an Australian level III adult intensive care unit. , 2004, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[23]  D. Coursin,et al.  Perioperative diabetic and hyperglycemic management issues , 2004, Critical care medicine.

[24]  T. Evans,et al.  Glucose control and mortality in critically ill patients. , 2004, JAMA.

[25]  Howard Cabral,et al.  Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events , 2004, Circulation.

[26]  Mitchell M. Levy,et al.  Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock , 2004, Critical care medicine.

[27]  M. Cakir,et al.  Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. , 2003, The Journal of clinical endocrinology and metabolism.

[28]  G. V. Berghe,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[29]  K. Malmberg Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus , 1997, BMJ.

[30]  J. Vincent,et al.  The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure , 1996, Intensive Care Medicine.

[31]  J Herlitz,et al.  Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): effects on mortality at 1 year. , 1995, Journal of the American College of Cardiology.

[32]  J. Newman,et al.  Hypoglycemia in hospitalized patients. Causes and outcomes. , 1986, The New England journal of medicine.

[33]  E. Draper,et al.  APACHE II: A severity of disease classification system , 1985, Critical care medicine.

[34]  A. B. Hill The Environment and Disease: Association or Causation? , 1965, Proceedings of the Royal Society of Medicine.

[35]  M. Özkaya,et al.  Action to Control Cardiovascular Risk in Diabetes , 2013 .

[36]  S. Schinner Effects of Intensive Glucose Lowering in Type 2 Diabetes , 2009 .

[37]  A. Bhalla,et al.  Images in clinical medicine. Paget's disease of the mandible. , 2008, The New England journal of medicine.

[38]  L. Robinson,et al.  Insulin resistance and hyperglycemia in critical illness: role of insulin in glycemic control. , 2004, AACN clinical issues.

[39]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.

[40]  Hypoglycemia in hospitalized patients. , 1987, The New England journal of medicine.