Stress-Induced Hyperglycemia in Diabetes: A Cross-Sectional Analysis to Explore the Definition Based on the Trauma Registry Data

Background: The diagnosis of diabetic hyperglycemia (DH) does not preclude a diabetes patient from having a stress-induced hyperglycemic response. This study aimed to define the optimal level of elevated glucose concentration for determining the occurrence of stress-induced hyperglycemia (SIH) in patients with diabetes. Methods: This retrospective study reviewed the data of all hospitalized trauma patients, in a Level I trauma center, from 1 January 2009 to 31 December 2016. Only adult patients aged ≥20 years, with available data on serum glucose and glycated hemoglobin A1c (HbA1c) levels upon admission, were included in the study. Long-term average glucose levels, as A1c-derived average glucose (ADAG), using the equation, ADAG = ((28.7 × HbA1c) − 46.7), were calculated. Patients with high glucose levels were divided into three SIH groups with diabetes mellitus (DM), based on the following definitions: (1) same glycemic gap from ADAG; (2) same percentage of elevated glucose of ADAG, from which percentage could also be reflected by the stress hyperglycemia ratio (SHR), calculated as the admission glucose level divided by ADAG; or (3) same percentage of elevated glucose as patients with a defined SIH level, in trauma patients with and without diabetes. Patients with incomplete registered data were excluded. The primary hypothesis of this study was that SIH in patients with diabetes would present worse mortality outcomes than in those without. Detailed data of SIH in patients with diabetes were retrieved from the Trauma Registry System. Results: Among the 546 patients with DH, 332 (32.0%), 188 (18.1%), and 106 (10.2%) were assigned as diabetes patients with SIH, based on defined glucose levels, set at 250 mg/dL, 300 mg/dL, and 350 mg/dL, respectively. In patients with defined cut-off glucose levels of 250 mg/dL and 300 mg/dL, SIH was associated with a 3.5-fold (95% confidence interval (CI) 1.61–7.46; p = 0.001) and 3-fold (95% CI 1.11–8.03; p = 0.030) higher odds of mortality, adjusted by sex, age, pre-existing comorbidities, and injury severity score, than the 491 patients with diabetic normoglycemia (DN). However, in patients with a defined cut-off glucose level of 350 mg/dL, adjusted mortality in SIH in DM was insignificantly different than that in DM. According to the receiver operating characteristic (ROC) curve analysis, a blood sugar of 233 mg/dL, a glycemic gap of 79 (i.e., blood sugar of 251 mg/dL), and a SHR of 1.45 (i.e., blood sugar of 250 mg/dL) were identified as cut-offs for mortality outcomes, with AUCs of 0.622, 0.653, and 0.658, respectively. Conclusions: In this study, a cut-off glucose level of 250 mg/dL was selected to provide a better definition of SIH in DM than glucose levels of 300 mg/dL or 350 mg/dL.

[1]  A. Sayed,et al.  Translating the A1C Assay into Estimated Average Glucose Values in Children with Type 1 Diabetes Mellitus , 2018 .

[2]  C. Rau,et al.  Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia, Is Associated with Higher Mortality in Patients with Isolated Moderate and Severe Traumatic Brain Injury: Analysis of a Propensity Score-Matched Population , 2017, International journal of environmental research and public health.

[3]  C. Rau,et al.  Higher Mortality in Trauma Patients Is Associated with Stress-Induced Hyperglycemia, but Not Diabetic Hyperglycemia: A Cross-Sectional Analysis Based on a Propensity-Score Matching Approach , 2017, International journal of environmental research and public health.

[4]  C. Hsieh,et al.  Motorcycle-related hospitalizations of the elderly , 2017, Biomedical journal.

[5]  Shiun-Yuan Hsu,et al.  Differences between the sexes in motorcycle-related injuries and fatalities at a Taiwanese level I trauma center , 2017, Biomedical journal.

[6]  Wen-I Liao,et al.  An Elevated Glycemic Gap is Associated with Adverse Outcomes in Diabetic Patients with Acute Myocardial Infarction , 2016, Scientific Reports.

[7]  Tariq M. Alhawassi,et al.  Relative Hyperglycemia, a Marker of Critical Illness: Introducing the Stress Hyperglycemia Ratio. , 2015, The Journal of clinical endocrinology and metabolism.

[8]  Wen-I Liao,et al.  Usefulness of Glycemic Gap to Predict ICU Mortality in Critically Ill Patients With Diabetes , 2015, Medicine.

[9]  Wen-I Liao,et al.  An Elevated Glycemic Gap is Associated With Adverse Outcomes in Diabetic Patients With Community-Acquired Pneumonia , 2015, Medicine.

[10]  M. Sabbe,et al.  Admission hyperglycaemia is associated with higher mortality in patients with hip fracture , 2015, European journal of emergency medicine : official journal of the European Society for Emergency Medicine.

[11]  P. Kalfon,et al.  Effects of tight computerized glucose control on neurological outcome in severely brain injured patients: a multicenter sub-group analysis of the randomized-controlled open-label CGAO-REA study , 2014, Critical Care.

[12]  Shuangshuang Cui,et al.  Stress-Induced Hyperglycemia After Hip Fracture and the Increased Risk of Acute Myocardial Infarction in Nondiabetic Patients , 2013, Diabetes Care.

[13]  J. Kerby,et al.  Stress-induced hyperglycemia: is it harmful following trauma? , 2013, Advances in surgery.

[14]  W. Sheu,et al.  An Elevated Gap between Admission and A1C-Derived Average Glucose Levels Is Associated with Adverse Outcomes in Diabetic Patients with Pyogenic Liver Abscess , 2013, PloS one.

[15]  P. Marik,et al.  Stress hyperglycemia: an essential survival response! , 2013, Critical Care.

[16]  Addison K. May,et al.  Stress-Induced Hyperglycemia as a Risk Factor for Surgical-Site Infection in Nondiabetic Orthopedic Trauma Patients Admitted to the Intensive Care Unit , 2013, Journal of orthopaedic trauma.

[17]  L. Rue,et al.  Stress-Induced Hyperglycemia, Not Diabetic Hyperglycemia, Is Associated With Higher Mortality in Trauma , 2012, Annals of surgery.

[18]  W. Obremskey,et al.  Relationship of hyperglycemia and surgical-site infection in orthopaedic surgery. , 2012, The Journal of bone and joint surgery. American volume.

[19]  Christina L. Jacovides,et al.  Perioperative Hyperglycemia and Postoperative Infection after Lower Limb Arthroplasty , 2011, Journal of diabetes science and technology.

[20]  R. Bellomo,et al.  The interaction of chronic and acute glycemia with mortality in critically ill patients with diabetes* , 2011, Critical care medicine.

[21]  P. O S I T I O N S T A T E M E N T,et al.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[22]  J. Vincent,et al.  Critical illness-induced dysglycaemia: diabetes and beyond , 2010, Critical care.

[23]  P. Zimmet,et al.  International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes , 2009, Diabetes Care.

[24]  M. Singer,et al.  Hyperglycemia in Critical Illness: A Review , 2009, Journal of diabetes science and technology.

[25]  J. Shaw,et al.  International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes , 2009, Diabetes Care.

[26]  Deborah J. Cook,et al.  Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data , 2009, Canadian Medical Association Journal.

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

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

[29]  D. Schoenfeld,et al.  Translating the A1C Assay Into Estimated Average Glucose Values , 2008, Diabetes Care.

[30]  H. Chandalia,et al.  STRESS HYPERGLYCAEMIA , 1984, The Lancet.

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

[32]  A. Malhotra,et al.  Stress-induced hyperglycemia. , 2001, Critical care clinics.