Stress-induced Hyperglycemia Research Articles

Perioperative evaluation of glycaemic status in neck dissection: a retrospective analysis at a single hospital centre

Diabetes mellitus is generally considered a risk factor for impaired wound healing. This study aimed to evaluate the glycaemic status of patients undergoing neck dissection and describe its impact on postoperative outcomes, especially wound healing. A retrospective analysis was performed of the preoperative, intraoperative, and postoperative glycaemic data obtained from the medical charts of 60 adult patients who had undergone 64 neck dissections. Nine of the 64 procedures were performed in diabetic patients (14.1%). The average glucose values were: preoperative 5.99±1.25mmol/l, intraoperative 8.90±2.62mmol/l, and postoperative 10.01±2.49mmol/l. All registered preoperative hyperglycaemia cases (eight cases) were diabetic. Postoperative insulin therapy was done in 14 procedures (21.9%). Wound healing complications were found in five patients (7.8%); there was no wound infection. There was no association of wound healing complications with preoperative diabetic status (P=1.000), preoperative glucose control (P=1.000), preoperative (P=0.469), intraoperative (P=0.248), and postoperative (P=0.158) glucose values, or with postoperative glucose control (P=0.577). These data do not support the association of stress-induced hyperglycaemia or diabetes mellitus with postoperative wound healing problems in neck dissection.

CRUSTACEAN HYPERGLYCEMIC HORMONE: STRUCTURAL VARIANTS, PHYSIOLOGICAL FUNCTION, AND CELLULAR MECHANISM OF ACTION

Crustacean hyperglycemic hormone (CHH) is a peptide hormone originally identified in the X-organ/sinus gland (XO/ SG) complex of the eyestalks. It belongs to the CHH family which also includes molt-inhibiting hormone (MIH), vitellogenesis-inhibiting hormone (VIH), and mandibular organ-inhibiting hormone (MOIH), and ion transport peptide (ITP). Multiple molecular variants of CHH are generated by both post-transcriptional and post-translational mechanisms. In addition to the XO/SG complex, CHH gene is widely expressed in many extra-eyestalk tissues. Functionally, available data indicate that CHH is involved with the regulation of carbohydrate metabolism and stress-induced hyperglycemia. Several other physiological processes, including molting, ion and water balance, reproduction, and immunity, are likely also regulated by CHH. The functional role(s) of the alternatively splice form CHH-like peptide (CHH-L) are different from those of CHH and remain unknown. Combined results showed that cyclic guanosine 3',5'-monophosphate (cGMP) plays important roles in mediating the effects of CHH on carbohydrate metabolism. Recent studies of receptor guanylyl cyclase (rGC) may lead to characterization and identification of CHH receptor(s). Future efforts are needed to fully understand the functional roles of the different CHH variants; identification of CHH receptor(s) hold the promise of revealing in greater depth the structure/functional relationships of the various structural variants.

Experimental and clinical evidences for glucose control in intensive care: is infused glucose the key point for study interpretation?

Stress-induced hyperglycemia has been considered an adaptive mechanism to stress up to the first intensive insulin therapy trial, which showed a 34% reduction in relative risk of in-hospital mortality when normalizing blood glucose levels. Further trials had conflicting results and, at present, stress-induced hyperglycemia management remains non-consensual. These findings could be explained by discrepancies in trials, notably regarding the approach to treat hyperglycemia: high versus restrictive caloric intake. Stress-induced hyperglycemia is a frequent complication during intensive care unit stay and is associated with a higher mortality. It results from an imbalance between insulin and counter-regulatory hormones, increased neoglucogenesis, and the cytokine-induced insulin-resistant state of tissues. In this review, we summarize detrimental effects of hyperglycemia on organs in the critically ill (peripheric and central nervous, liver, immune system, kidney, and cardiovascular system). Finally, we show clinical and experimental evidence of potential benefits from glucose and insulin administration, notably on metabolism, immunity, and the cardiovascular system.

Glycated hemoglobin A: A predictor of outcome in trauma admissions to intensive care unit

Background and Aim:Although large studies have demonstrated the association between hyperglycemia and adverse intensive care unit (ICU) outcomes, it is yet unclear which subset of patients benefit from tight sugar control in ICU. Recent evidence suggests that stress induced hyperglycemia (SIH) and co-incidentally detected diabetes mellitus are different phenomena with different prognoses. Differentiating SIH from diabetic hyperglycemia is challenging in ICU settings. We followed a cohort of trauma patients admitted to a surgical intensive care unit (SICU) to evaluate if initial glycated hemoglobin A (HbA1c) level predicts the outcome of admission.Materials and Methods:A cohort of 120 consecutive admissions to SICU following trauma were recruited and admission blood sugar and HbA1c were measured. Outcomes were prospectively measured by blinded ICU doctors. A logistic regression model was developed to assess if HbA1c predicts poor outcomes in these settings.Results:Nearly 24% of the participants had HbA1c ≥ 6. Those with HbA1c ≥ 6 had 3.14 times greater risk of poor outcome at the end of hospital stay when compared to those with HbA1c < 6 and this risk increased to an odds ratio of 4.57 on adjusting for other significant predictors: Acute Physiology and Chronic Health Evaluation II, injury severity score, admission blood sugar and age at admission.Conclusions:Substantial proportion of trauma admissions has underlying diabetes. HbA1c, a measure of pre admission glycaemic status is an important predictor of ICU outcome in trauma patients.

Association between glycemic variability and mortality: How robust is the evidence?

Association between glycemic variability and mortality: How robust is the evidence?

Survey about diffusion and adoption of glycaemic controller in European intensive care units

Stress-induced hyperglycaemia and glycaemic variability are both associated with worsened critically ill patient outcome. Glycaemic control (GC) aims to reduce and stabilize blood glucose (BG) levels, while minimizing hypoglycaemic risk. Several national surveys have been carried out about GC in intensive care unit (ICU). They mainly focused on characteristics of a GC protocol in terms of glycaemic target, on hyper/hypo-glycaemic thresholds and on the association between glycaemic levels and patient outcome. This survey aims to have a more overall European overview about GC, and more especially about the interest of medical staff for GC systems in European ICUs and the clinician specified key success factors related for these systems. This survey was conducted with 52 persons related to ICUs from 18 different European countries. Results show that some ICU clinicians (10/52, 19.2 %) are still reluctant to implement GC and attention should be paid to overcome their specific criticisms to aid the uptake of safe, effective GC systems. In particular, control-related issues of GC target and used centred on fear of hypoglycaemia. Clinicians thus preferred model-based systems (19/52, 36.5 %), especially if they could forecast the risk of hypoglycaemia. This survey results have highlighted the definition of key control issues by the end-user.

Glycaemic control in the perioperative period

The prevalence of type 2 diabetes mellitus and the potential for perioperative dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or glucose variability) continue to increase dramatically. The majority of investigations on perioperative glycaemic control focused on critically ill patients and concentrated on goals of therapy, level of intensity of insulin infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of recent guidelines calling for less strict glucose control. Areas of perioperative glycaemic control that deserve further investigation include preoperative identification of patients with undiagnosed type 2 diabetes and other forms of dysglycaemia, determination of appropriate intraoperative glucose goals, and establishment of the impact and natural history of perioperative abnormalities in glucose homeostasis. In the heterogeneous adult perioperative population, it is unlikely that one standard of perioperative glycaemic control is appropriate for all patients. This review presents recent evidence and expert guidance to aid preoperative assessment, intraoperative management, and postoperative care of the dysglycaemic adult patient.

Complexity of Continuous Glucose Monitoring Data in Critically Ill Patients: Continuous Glucose Monitoring Devices, Sensor Locations, and Detrended Fluctuation Analysis Methods

Critically ill patients often experience high levels of insulin resistance and stress-induced hyperglycemia, which may negatively impact outcomes. However, evidence surrounding the causes of negative outcomes remains inconclusive. Continuous glucose monitoring (CGM) devices allow researchers to investigate glucose complexity, using detrended fluctuation analysis (DFA), to determine whether it is associated with negative outcomes. The aim of this study was to investigate the effects of CGM device type/calibration and CGM sensor location on results from DFA. This study uses CGM data from critically ill patients who were each monitored concurrently using Medtronic iPro2s on the thigh and abdomen and a Medtronic Guardian REAL-Time on the abdomen. This allowed interdevice/calibration type and intersensor site variation to be assessed. Detrended fluctuation analysis is a technique that has previously been used to determine the complexity of CGM data in critically ill patients. Two variants of DFA, monofractal and multifractal, were used to assess the complexity of sensor glucose data as well as the precalibration raw sensor current. Monofractal DFA produces a scaling exponent (H), where H is inversely related to complexity. The results of multifractal DFA are presented graphically by the multifractal spectrum. From the 10 patients recruited, 26 CGM devices produced data suitable for analysis. The values of H from abdominal iPro2 data were 0.10 (0.03-0.20) higher than those from Guardian REAL-Time data, indicating consistently lower complexities in iPro2 data. However, repeating the analysis on the raw sensor current showed little or no difference in complexity. Sensor site had little effect on the scaling exponents in this data set. Finally, multifractal DFA revealed no significant associations between the multifractal spectrums and CGM device type/calibration or sensor location. Monofractal DFA results are dependent on the device/calibration used to obtain CGM data, but sensor location has little impact. Future studies of glucose complexity should consider the findings presented here when designing their investigations.

Glucose Metabolism in Critically Ill Patients

Critical illness afflicts millions of people worldwide and is associated with a high risk of organ failure and death or an adverse outcome with persistent physical or cognitive deficits. Spontaneous hyperglycemia is common in critically ill patients and is associated with an adverse outcome compared to normoglycemia. Insulin is used for treating hyperglycemia in the critically ill patients but may be complicated by hypoglycemia, which is difficult to detect in these patients and which may lead to serious neurological sequelae and death. The incretin hormone, glucagon-like peptide (GLP) 1, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar characteristics and are, among other things, both characterized by different grades of systemic inflammation and insulin resistance. The GLP-1 might be a potential new treatment target in critically ill patients with stress-induced hyperglycemia.

Stress-Induced Hyperglycemia After Hip Fracture and the Increased Risk of Acute Myocardial Infarction in Nondiabetic Patients

OBJECTIVETo investigate the risk of acute myocardial infarction (AMI) following stress hyperglycemia after hip fracture.RESEARCH DESIGN AND METHODSFrom February 2007 to February 2012, we carried out a prospective observational analysis of 1,257 consecutive patients with no history of diabetes who suffered hip fractures. Fasting blood glucose (FBG) and glycosylated hemoglobin tests as well as electrocardiography, ultrasonic cardiography, and chest X-ray examinations were performed after admission. All selected hip fracture patients were divided into stress hyperglycemia and non-hyperglycemia groups according to their FBG, and the incidence of AMI was monitored.RESULTSAmong the patients enrolled, the frequency of stress hyperglycemia was 47.89% (602/1,257) and that of AMI was 9.31% (117/1,257), and the occurrence of AMI in the stress hyperglycemia group was higher than in the non-hyperglycemia group (12.46 vs. 6.41%, P < 0.05). In the stress hyperglycemia patients, FBG reached maximum levels at 2–3 days after hip fractures and then decreased gradually. The AMI incidence (62.67% [47/75]) of the stress hyperglycemia group was highest in the initial 3 days after hip fracture, significantly coinciding with the FBG peak time (P < 0.05). In all patients with AMI, non–ST-segment elevation myocardial infarction occurred more often than ST-segment elevation myocardial infarction (62.39% [73/117] vs. 37.61% [44/117]).CONCLUSIONSStress-induced hyperglycemia after hip fracture increased the risk of AMI.

Blood glucose level as an insufficient indicator of feline diabetes mellitus: a case report

In several European countries (e.g., Poland) blood glucose level is the main indicator of feline diabetes mellitus. We describe a case of an adult domestic cat (Felis catus) that exhibited no symptoms of diabetes except high glucose level in blood (&amp;asymp;200 mg/dl) that indicated a possibility of early stage of this disease. However, further investigations including serum fructosamine level determination, systematic urine monitoring as well as comparative analyses of glucose level in blood samples collected at the veterinary clinic and at home revealed that the cat was suffering from stress-induced hyperglycaemia brought on by the car ride and visit to the veterinary clinic. This case highlights the fact that determining blood glucose level alone is insufficient in feline diabetes mellitus diagnosis and can lead to unnecessary treatment with potential adverse effects on feline health. &amp;nbsp; &amp;nbsp;

An Elevated Gap between Admission and A1C-Derived Average Glucose Levels Is Associated with Adverse Outcomes in Diabetic Patients with Pyogenic Liver Abscess

ObjectivesTo assess whether chronic glycemic control and stress-induced hyperglycemia, determined by the gap between admission glucose levels and A1C-derived average glucose (ADAG) levels adversely affects outcomes in diabetic patients with pyogenic liver abscess (PLA).MethodsClinical, laboratory, and multi-detector computed tomography (MDCT) findings of 329 PLA patients (2004–2010) were retrospectively reviewed. HbA1C levels were used to determine long-term glycemic control status, which were then converted to estimated average glucose values. For the gap between admission glucose levels and ADAG levels, we used receiver operating characteristic (ROC) curve to determine the optimal cut-off values predicting adverse outcomes. Univariate and multivariate logistic regressions were used to identify predictors of adverse outcomes.ResultsDiabetic PLA patients with poorer glycemic control had significantly higher Klebsiella pneumoniae (KP) infection rates, lower albumin levels, and longer hospital stays than those with suboptimal and good glycemic control. The ROC curve showed that a glycemic gap of 72 mg/dL was the optimal cut-off value for predicting adverse outcomes and showed a 22.3% relative increase in adverse outcomes compared with a glycemic gap<72 mg/dL. Multivariate analysis revealed that an elevated glycemic gap≥72 mg/dL was important predictor of adverse outcomes.ConclusionsA glycemic gap≥72 mg/dL, rather than admission hyperglycemia or chronic glycemic control, was significantly correlated with adverse outcomes in diabetic PLA patients. Poorer chronic glycemic control in diabetic PLA patients is associated with high incidence of KP infection, hypoalbuminemia and longer hospital stay.

In-Hospital Management of Diabetes.

In-Hospital Management of Diabetes.

In-hospital Management of Diabetes

In-hospital Management of Diabetes

Stress-induced hyperglycemia is a valuable biomarker in febrile neutropenia.

Stress-induced hyperglycemia is a valuable biomarker in febrile neutropenia.

Pattern of Stress-Induced Hyperglycemia according to Type of Diabetes: A Predator Stress Model

BackgroundWe aimed to quantify stress-induced hyperglycemia and differentiate the glucose response between normal animals and those with diabetes. We also examined the pattern in glucose fluctuation induced by stress according to type of diabetes.MethodsTo load psychological stress on animal models, we used a predator stress model by exposing rats to a cat for 60 minutes and measured glucose level from the beginning to the end of the test to monitor glucose fluctuation. We induced type 1 diabetes model (T1D) for ten Sprague-Dawley rats using streptozotocin and used five Otsuka Long-Evans Tokushima Fatty rats as obese type 2 diabetes model (OT2D) and 10 Goto-Kakizaki rats as nonobese type 2 diabetes model (NOT2D). We performed the stress loading test in both the normal and diabetic states and compared patterns of glucose fluctuation among the three models. We classified the pattern of glucose fluctuation into A, B, and C types according to speed of change in glucose level.ResultsIncrease in glucose, total amount of hyperglycemic exposure, time of stress-induced hyperglycemia, and speed of glucose increase were significantly increased in all models compared to the normal state. While the early increase in glucose after exposure to stress was higher in T1D and NOT2D, it was slower in OT2D. The rate of speed of the decrease in glucose level was highest in NOT2D and lowest in OT2D.ConclusionThe diabetic state was more vulnerable to stress compared to the normal state in all models, and the pattern of glucose fluctuation differed among the three types of diabetes. The study provides basic evidence for stress-induced hyperglycemia patterns and characteristics used for the management of diabetes patients.

Stress-induced Hyperglycemia, Not Diabetic Hyperglycemia, is Associated with Higher Mortality in Trauma: Kerby JD, Griffin RL, MacLennan P, et al. Ann Surg 2012;256:446–52.

Hyperglycemia is a normal physiologic response to stress, but may also be due to underlying diabetes mellitus. Regardless of the etiology, hyperglycemia has been shown to adversely affect outcomes in a variety of patient populations. Whereas prior studies have shown higher mortality rates in hyperglycemic trauma patients, no study has differentiated between stress-induced hyperglycemia (SIH) and diabetes mellitus (DM).

Stress-Induced Hyperglycemia as a Risk Factor for Surgical-Site Infection in Nondiabetic Orthopedic Trauma Patients Admitted to the Intensive Care Unit

The aim of this study was to evaluate the association between stress-induced hyperglycemia and infectious complications in nondiabetic orthopedic trauma patients admitted to the intensive care unit (ICU). : This study was a retrospective review. The study was conducted at an academic level-1 trauma center. One hundred and eighty-seven consecutive trauma patients with isolated orthopedic injuries were studied. : Blood glucose values during initial hospitalization were evaluated. The admission blood glucose (BG) and hyperglycemic index (HGI) were determined for each patient. Perioperative infectious complications: pneumonia, urinary tract infection (UTI), surgical-site infection (SSI), sepsis were the outcome measures. An average of 21.5 BG values was obtained for each patient. The mean ICU and hospital length of stay was 4.0 ± 4.9 and 10.0 ± 8.1 days, respectively. Infections were recorded in 43 of 187 patients (23.0%) and SSIs specifically documented in 16 patients (8.6%). Open fractures were not associated with SSI (8/83, 9.6% vs. 8/104, 7.7%). There was no difference in admission BG or HGI and infection. However, there was a significant difference in HGI when considering SSI alone (2.1 ± 1.7 vs. 1.2 ± 1.1). Patients with an SSI received a greater amount of blood transfusions (14.9 ± 12.1 vs. 4.9 ± 7.6). No patient was diagnosed with a separate infection (ie, pneumonia, UTI, bacteremia) before SSI. There was no significant difference in injury severity score among patients with an SSI (11.1 ± 4.0 vs. 9.6 ± 3.0). Multivariable regression testing with HGI as a continuous variable demonstrated a significant relationship (odds ratio: 1.8, 95% confidence interval: 1.3-2.5) with SSI after adjusting for blood transfusions (odds ratio: 1.1, 95% confidence interval: 1.1-1.2). : Stress-induced hyperglycemia demonstrated a significant independent association with SSIs in nondiabetic orthopedic trauma patients who were admitted to the ICU. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Benefits of intensive insulin therapy in post-operative intensive care patients

Patients without diabetes who have surgery often develop elevated blood glucose levels. This article describes the effects of stress on blood glucose levels and the importance of treating stress-induced hyperglycaemia in surgical patients. It suggests that all patients with or without diabetes could benefit from the maintenance of strict blood glucose control within set parameters during and after surgery. The evidence suggests that strict control of blood glucose levels and frequent monitoring and maintenance of normoglycaemia may reduce post-operative complications and promote better patient long-term outcomes. The use of intensive insulin therapy is recommended for all post-operative patients in intensive care.

Haemoglobin A1c, acute hyperglycaemia and short-term prognosis in patients without diabetes following acute ST-segment elevation myocardial infarction

To assess the prognostic impact of HbA(1c) and blood glucose level in patients with acute ST-segment elevation myocardial infarction and without diabetes. The relationship between HbA(1c) and acute hyperglycaemia was also explored. We evaluated 4793 ST-segment elevation myocardial infarction patients with baseline HbA(1c) and three glucose measurements in the first 24 h. First, patients were stratified into quintiles by HbA(1c) and mean/admission glucose level. A total of 373 deaths (7.8%) occurred at 7 days, and 486 deaths (10.1%) occurred at 30 days. There were no significant differences in 7- and 30-day mortality, and major adverse cardiovascular event rates across HbA(1c) quintiles (< 34.4 mmol/mol (5.3% ), 34.4 to < 37.7 mmol/mol (5.6%), 37.7 to < 41.0 mmol/mol (5.9% ), 41.0 to < 47.5 mmol/mol (6.5%), and ≥ 47.5 mmol/mol; P for trend > 0.05). The risks of mortality and major adverse cardiovascular events were significantly increased in patients with higher glucose quintiles and lower quintile compared with the middle quintile after multivariable adjustment (P < 0.001). Patients were then reclassified into four groups according to mean/admission glucose and HbA(1c) levels. The group with elevated glucose and non-elevated HbA(1c) was associated with the highest mortality and major adverse cardiovascular event risk (P < 0.001). Unlike acute hyperglycaemia, an elevated HbA(1c) level was not a risk factor for short-term outcomes in ST-segment elevation myocardial infarction patients without diabetes. Patients with acute hyperglycaemia and non-elevated HbA(1c) were associated with the worst prognosis. That suggests chronic glycaemic control/HbA(1c) level may help to recognize stress-induced hyperglycaemia and identify high-risk patients.