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

Rau, Cheng-Shyuan; Wu, Shao-Chun; Chen, Yi‐Chun; Chien, Peng‐Chen; Hsieh, Hsiao-Yun; Kuo, Pao‐Jen; Hsieh, Ching‐Hua

doi:10.3390/ijerph14101161

Cited by 34 publications

(33 citation statements)

References 30 publications

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“…The above adjustments are expected to reduce bias in the assessment of mortality outcomes and infer a different extent of the odds of mortality. An adjustment to reduce bias in comparison is important during the assessment; for example, our previous study which explored the morbidities associated with SIH for all trauma patients had revealed that even the SIH had a 2.9-fold higher odds of pneumonia (95% CI 1.68–4.93; p < 0.001) and a 4.8-fold higher odds of acute renal failure (95% CI 2.15–10.52; p < 0.001) than the NDN, there were no differences in the rates of pneumonia and acute renal failure between SIH and NDN after adjustment by propensity-score matching [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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

Rau

Chen

et al. 2017

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Background: Admission hyperglycemia is associated with higher morbidity and mortality in patients with traumatic brain injury (TBI). Stress-induced hyperglycemia (SIH), a form of hyperglycemia induced by the stress response, is associated with increased patient mortality following TBI. However, admission hyperglycemia occurs not only in SIH but also in patients with diabetic hyperglycemia (DH). Current information regarding whether trauma patients with SIH represent a distinct group with differential outcomes compared to those with DH remains limited. Methods: Serum glucose concentration ≥200 mg/dL upon arrival at the emergency department was defined as hyperglycemia. Presence of diabetes mellitus (DM) was determined by patient history and/or admission glycated hemoglobin (HbA1c) level ≥6.5%. In the present study, the patient cohort included those with moderate and severe TBI, as defined by an Abbreviated Injury Scale (AIS) score ≥3 points in the head, and excluded those who had additional AIS scores ≥3 points in any other region of the body. A total of 1798 adult patients with isolated moderate to severe TBI were allocated into four groups: SIH (n = 140), DH (n = 187), diabetic normoglycemia (DN, n = 186), and non-diabetic normoglycemia (NDN, n = 1285). Detailed patient information was retrieved from the Trauma Registry System at a level I trauma center between 1 January 2009, and 31 December 2015. Unpaired Student’s t- and Mann–Whitney U-tests were used to analyze normally and non-normally distributed continuous data, respectively. Categorical data were compared using the Pearson chi-square or two-sided Fisher’s exact tests. Matched patient populations were allocated in a 1:1 ratio according to propensity scores calculated by NCSS software. Logistic regression was used to evaluate the effect of SIH and DH on the adjusted mortality outcome. Results: In patients with isolated moderate to severe TBI, the presence of SIH and DH led to 9.1-fold and 2.3-fold higher odds of mortality, respectively, than patients with NDN. After adjusting for confounding factors, including sex and age, pre-existing co-morbidities, existence of different kinds of intracerebral hemorrhage, and injury severity, patients with SIH still had 6.6-fold higher odds of mortality than those with NDN; however, DH did not present significantly higher adjusted mortality odds. SIH and DH presented different effects on outcomes after TBI. The results also suggested that the pathophysiological effect associated with SIH was different from that of DH. Conclusions: This study demonstrated that patients with SIH and DH had significantly higher mortality than patients with NDN. However, the adjusted mortality was significantly higher only in the selected propensity score-matched patients with SIH and not in those with DH.

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Section: Discussionmentioning

confidence: 99%

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

Rau

Chen

et al. 2017

IJERPH

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“…This second definition, based on similar percentages of glucose elevation, both in patients with and without diabetes, is more reasonable, because the admission glucose level is at 1.3-fold of ADAG, in both patients with and without diabetes with a similar severity of injury in this study. Under the hypothesis that stress presumably caused a similar percentage of glucose increase both in patients with and without diabetes, in the second definition (glucose level of ≥300 mg/dL), the SIH in DM had a 3-fold higher odds of adjusted mortality than DN, which is comparable with the 3-fold adjusted mortality of SIH in patients without diabetes, compared to NDN [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…SIH is attributed to a state of excess hepatic glucose output, diminished insulin production, and insulin resistance in the peripheral tissues, with excessive adrenal cortical output and high circulating levels of cytokines [ 5 , 6 ]. The prevalence of SIH has been reported as 4% [ 7 ] and 4.9% [ 8 ] of patients with all trauma causes to 7.8% of patients with isolated moderate to severe trauma brain injuries [ 9 ] and up to 48.9% of patients with a hip fracture [ 10 ]. It is also associated with increased in-hospital mortality, especially in patients without diabetes [ 7 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Kerby et al, reported that SIH demonstrated a >2-fold increase in mortality risk; however, diabetic hyperglycemia (DH) was not associated with a significantly high mortality risk (RR 1.47, 95% CI 0.92–2.36) in trauma patients [ 7 ]. Our previous study also revealed that SIH had a 3-fold higher odds ratio (OR) of mortality (95% CI 1.96–4.49; p < 0.001) than non-diabetic normoglycemia (NDN), in the selected propensity score-matched patient population, controlled by age, sex, pre-existing comorbidities, and injury severity score (ISS) [ 8 ]. However, the mortality rate in DH (OR 1.2, 95% CI 0.99–1.38; p = 0.065) was insignificantly higher than that in NDN [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study also revealed that SIH had a 3-fold higher odds ratio (OR) of mortality (95% CI 1.96–4.49; p < 0.001) than non-diabetic normoglycemia (NDN), in the selected propensity score-matched patient population, controlled by age, sex, pre-existing comorbidities, and injury severity score (ISS) [ 8 ]. However, the mortality rate in DH (OR 1.2, 95% CI 0.99–1.38; p = 0.065) was insignificantly higher than that in NDN [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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

Rau

Chen

et al. 2017

IJERPH

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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.

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Patterns and Effects of Admission Hyperglycemia and Inflammatory Response in Trauma Patients: A Prospective Clinical Study

et al. 2021

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Background The constellation of the initial hyperglycemia, proinflammatory cytokines and severity of injury among trauma patients is understudied. We aimed to evaluate the patterns and effects of on-admission hyperglycemia and inflammatory response in a level 1 trauma center. We hypothesized that higher initial readings of blood glucose and cytokines are associated with severe injuries and worse in-hospital outcomes in trauma patients. Methods A prospective, observational study was conducted for adult trauma patients who were admitted and tested for on-admission blood glucose, hemoglobin A1c, interleukin (IL)-6, IL-18 and hs-CRP. Patients were categorized into four groups [non-diabetic normoglycemic, diabetic normoglycemic, diabetic hyperglycemic (DH) and stress-induced hyperglycemic (SIH)]. The inflammatory markers were measured on three time points (admission, 24 h and 48 h). Generalized estimating equations (GEE) were used to account for the correlation for the inflammatory markers. Pearson’s correlation test and logistic regression analysis were also performed. Results During the study period, 250 adult trauma patients were enrolled. Almost 13% of patients presented with hyperglycemia (50% had SIH and 50% had DH). Patients with SIH were younger, had significantly higher Injury Severity Score (ISS), higher IL-6 readings, prolonged hospital length of stay and higher mortality. The SIH group had lower Revised Trauma Score (p = 0.005), lower Trauma Injury Severity Score (p = 0.01) and lower GCS (p = 0.001). Patients with hyperglycemia had higher in-hospital mortality than the normoglycemia group (12.5% vs 3.7%; p = 0.02). A significant correlation was identified between the initial blood glucose level and serum lactate, IL-6, ISS and hospital length of stay. Overall rate of change in slope 88.54 (95% CI:-143.39–33.68) points was found more in hyperglycemia than normoglycemia group (p = 0.002) for IL-6 values, whereas there was no statistical significant change in slopes of age, gender and their interaction. The initial IL-6 levels correlated with ISS (r = 0.40, p = 0.001). On-admission hyperglycemia had an adjusted odds ratio 2.42 (95% CI: 1.076–5.447, p = 0.03) for severe injury (ISS > 12) after adjusting for age, shock index and blood transfusion. Conclusions In trauma patients, on-admission hyperglycemia correlates well with the initial serum IL-6 level and is associated with more severe injuries. Therefore, it could be a simple marker of injury severity and useful tool for patient triage and risk assessment. Trial registration This study was registered at the ClinicalTrials.gov (Identifier: NCT02999386), retrospectively Registered on December 21, 2016. https://clinicaltrials.gov/ct2/show/NCT02999386.

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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

Cited by 34 publications

References 30 publications

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

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

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

Patterns and Effects of Admission Hyperglycemia and Inflammatory Response in Trauma Patients: A Prospective Clinical Study

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