Stress-induced Hyperglycemia Research Articles

The Interaction and Implication of Stress-Induced Hyperglycemia and Cytokine Release Following Traumatic Injury: A Structured Scoping Review

This is a structured scoping review to assess whether there is a relationship between stress-induced hyperglycemia (SIH), cytokine interactions, and mortality in trauma patients in comparison to non-diabetic normoglycemia [NDN], diabetic normoglycemia [DN], and diabetic hyperglycemia [DH]. We conducted a literature search of MEDLINE (PubMed) databases from 2000 to 2022 using a search strategy to identify observational studies. Initially, 2879 articles were retrieved. Of these, 2869 were excluded due to insufficient variables, and non-trauma focuses. Nine studies on the interaction between SIH and proinflammatory cytokines were analyzed. SIH was associated with the highest mortality rate (21.3%), followed by DH (5.4%), DN (2.8%), and NDN (2.3%) (p < 0.001). Furthermore, SIH patients exhibited an 11.28-fold higher likelihood of mortality compared to NDN patients (95% CI [9.13–13.93]; p < 0.001) and a 4.72-fold higher likelihood compared to DH patients (OR 4.72; 95% CI [3.55–6.27]; p < 0.001). SIH patients had elevated IL-6 concentrations relative to NDN, DN, and DH patients. SIH is linked to higher mortality in trauma, with greater odds than NDN. However, the robustness of this association is still being determined due to statistical and clinical variability. Uncertainties about injury severity and IL-6 level similarities between SIH and DH patients require further investigation.

Association of Neutrophil extracellular traps burden with clinical and angiographic characteristics in patients with ST-elevation myocardial infarction

Abstract Background The precise triggers for arterial plaque rupture and the underlying pathophysiology of thrombogenesis remain elusive. Polymorphonuclear neutrophils (PMN), particularly their formation of Neutrophil Extracellular Traps (NETs), have garnered attention in the context of coronary atherothrombosis. This study sought to explore the association of NETs burden with clinical and angiographic characteristics in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) and thrombus aspiration (TA). Methods This study included 336 consecutive STEMI patients undergoing pPCI and TA. Aspirated thrombi underwent histological analysis and NETs quantification via immunohistochemistry. Potential associations of clinical variables and angiographic outcomes with NETs burden were assessed. Results Manual TA was selectively performed in 72 cases with increased thrombotic burden and 60 thrombi were suitable for analysis. Most thrombi specimens displayed lytic features (63%) and almost three out of four specimens were identified as white thrombi. Increased NETs burden was significantly associated with prolonged pain-to-balloon time (>300 minutes) OR=10.29 (95% CI 2.11-42.22, p=0.001) and stress-induced hyperglycemia (SIH) OR=6.58 (95% CI 1.23-52.63, p=0.04) after multivariate regression analysis. Additionally, distal embolization (DE), a predictor of adverse outcomes, was more frequent among patients with an elevated NETs burden OR=16.9 (95% CI 4.23-44.52, p<0.001). Conversely, no significant association between NETs burden and final TIMI flow=3 was observed. Conclusion Elevated NETs burden in STEMI thrombi is linked to delayed reperfusion, SIH and increased risk of DE. Further research is needed to elucidate the role of NETs as a potential therapeutic target in acute atherothrombosis.

Predicting the impact of stress-induced hyperglycemia on in-hospital mortality in patients with chronic kidney disease and acute coronary syndrome: A retrospective study

BackgroundStress hyperglycemia is prevalent in critical illnesses and has been associated with adverse short- and long-term outcomes in individuals with acute coronary syndrome (ACS). However, there is limited evidence for the predictive value of stress hyperglycemia and hospitalization mortality in patients with chronic kidney disease (CKD) and ACS. This study aimed to explore the association between hospitalized mortality, stress hyperglycemia ratio (SHR), and admission blood glucose (ABG) in patients with CKD and ACS. MethodsThis study included 655 hospitalized patients who were diagnosed with ACS and CKD. Patients with incomplete data were excluded, resulting in the analysis of 550 patients. The primary outcome measured was in-hospital mortality. ResultsThe median age of the cohort included in the analysis was 71 years, with a male proportion of 66.2 %, and a mean estimated glomerular filtration rate (eGFR) of 27.8 mL/min/1.73 m2. Patients classified as having stage 3, stage 4, and stage 5 chronic kidney disease (CKD) comprised 46.9 %, 17.1 %, and 36.0 % of the population, respectively. The overall in-hospital mortality rate was 10.7 % (n = 59). Both SHR (OR = 2.67; 95 % CI 1.51–4.74; p < 0.001) and ABG (OR = 1.09; 95 % CI 1.04–1.14; p < 0.001) were significantly associated with in-hospital mortality in CKD and ACS patients. SHR and ABG showed a linear relationship with in-hospital mortality, with SHR demonstrating superior reclassification ability over ABG. The inclusion of SHR or ABG, irrespective of diabetes mellitus status, substantially enhanced the predictive performance of the Global Registry of Acute Coronary Events (GRACE) score model. ConclusionsIn patients with ACS and CKD, a robust correlation was observed between SHR, ABG, and in-hospital mortality. Both SHR and ABG improved the predictive accuracy of the GRACE score in forecasting inpatient mortality in this population.

The predictive value of stress-induced hyperglycemia parameters for delayed healing after tibial fracture post-surgery

PurposeThe objective of this retrospective cohort study was to investigate the predictive value of stress-induced hyperglycemia parameters for delayed healing after tibial fracture post-surgery.MethodsA cohort of 108 participants who underwent surgical intervention for tibial fractures caused by trauma was included in this retrospective study. Data collected from electronic medical records encompassed demographic characteristics, bone healing assessments, stress-induced hyperglycemia parameters, inflammatory markers, and stress-related hormones. Comparative analyses, correlation analyses, univariate logistic regression analyses, and receiver operating characteristic (ROC) curve analyses were conducted to assess the predictive value of the studied parameters.ResultsThe delayed healing group exhibited higher levels of fasting blood glucose, postprandial glucose, and HbA1c, as well as elevated levels of inflammatory markers and stress-related hormones compared to the normal healing group. Correlation analysis and logistic regression demonstrated positive associations between stress-induced hyperglycemia parameters, inflammatory markers, stress-related hormones, and delayed union of tibial fractures (R2: 0.183 ~ 0.403;OR: 1.091 ~ 16.332). ROC curve analysis revealed high area under the curve (AUC = 0.911) values for stress-induced hyperglycemia parameters, indicating their potential as predictive markers for delayed healing. Multivariate regression analysis further substantiated the predictive capability of stress-induced hyperglycemia parameters.ConclusionThe study findings highlight the complex interplay between stress-induced hyperglycemia, inflammatory response, and bone healing outcomes in patients undergoing surgical intervention for tibial fractures. The identification of stress-induced hyperglycemia parameters as potential predictive markers for delayed healing after tibial fracture surgery offers insights for risk assessment and patient management, emphasizing the need for comprehensive understanding of these factors to optimize postoperative recovery in orthopedic patients.

Hypothalamus-sympathetic-liver axis mediates the early phase of stress-induced hyperglycemia in the male mice

Rapid glucose supply is crucial for animal survival during stress response. How the timescale of stress-induced glucose release precisely controlled by hypothalamic corticotropin-releasing hormone (CRH) neurons remains unclear. Here, we show that stress-induced hyperglycemia can be divided into at least two stages in male mice: the first fast stage is mediated by hypothalamus (paraventricular to ventromedial hypothalamus)-sympathetic (raphe pallidus nucleus to intermediolateral nucleus)-liver (HSL) axis activity; the second delayed stage is mediated by adrenal activity. Blocking the activity of HSL axis impairs predatory evoked flight responses, indicating that the HSL pathway activity is necessary for stress coping. We further reveal the intracellular signal cascade for CRH signal in the hypothalamus, which is mediated by GABAA receptor β3 subunit phosphorylation at S408/409, results in prevention of GABAA receptor membrane recruitment. Thus, we uncovered the precise timescale of glucose supply during stress which is mediated by adrenal independent HSL and adrenal dependent pathway respectively.

The measurement of plasma fructosamine as a diagnostic tool to improve the interpretation of plasma glucose and proteins in alpacas (Vicugna pacos).

This study assesses the use of fructosamine as a diagnostic tool for hyperglycemia in alpacas in view of their sensitivity to stress and susceptibility to conditions like lipid mobilization syndrome. Plasma fructosamine, like in diagnosing diabetes in cats and dogs, can reveal long-term blood glucose trends, differentiating stress-induced spikes from persistent diabetic hyperglycemia. In 125 alpacas presented as patients of a veterinary clinic, plasma glucose and fructosamine concentrations were compared for correlations with findings of the general clinical examination, laboratory parameters, demographic data, and a behavioral stress assessment processed by using principal component analysis. Hyperglycemia was observed on admission of 71% (89/125) of the animals. This was significantly associated with a higher concentration of serum cortisol and a higher behavioral stress scoring. Fructosamine above the reference limit was detected in only 15% (13/89) of the hyperglycemic individuals. In addition to a positive correlation of fructosamine to glucose concentration, positive relationships with different plasma proteins were detected. A relationship to stress parameters was not observed. These findings underscore stress as a significant trigger for hyperglycemia in alpacas and suggest fructosamine as a valuable parameter for distinguishing between stress-induced and diabetic hyperglycemia. However, the dependence of fructosamine formation on total plasma protein concentration should be considered to avoid misinterpretation.

Stress-induced hyperglycemia and mortality in patients with traumatic brain injury without preexisting diabetes: A meta-analysis.

Stress-induced hyperglycemia (SIH) is common in patients with traumatic brain injury (TBI) and has been suggested to influence mortality rates. This meta-analysis aims to evaluate the impact of SIH on the mortality of TBI patients without preexisting diabetes mellitus (DM). A comprehensive search was performed in Medline, Web of Science, Embase, Wanfang, and CNKI databases up to May 15, 2024, to retrieve relevant studies. Observational studies reporting the incidence of all-cause mortality among TBI patients without preexisting DM, comparing those with and without SIH, were included. The association between SIH and all-cause mortality was analyzed using risk ratios (RR) and 95% confidence intervals (CI) with a random-effects model. Twelve cohort studies comprising 15 datasets with 16,387 TBI patients were included. The pooled analysis showed that SIH was associated with a higher risk of all-cause mortality (RR: 2.00, 95% CI: 1.72-2.33, p < 0.001), with mild heterogeneity (I² = 25%). Sensitivity analysis confirmed the robustness of these findings. Subgroup analyses indicated no significant differences based on study design, patient age, gender proportion, SIH definition, or follow-up duration. However, the association was slightly weaker but still significant in studies using multivariate analyses (RR: 1.76) compared to univariate analyses (RR: 2.69). In conclusion, SIH was associated with a higher risk of all-cause mortality in TBI patients without preexisting DM. Further research should explore the underlying mechanisms and optimal management strategies for SIH in this population.

Association between the stress hyperglycemia ratio and mortality in patients with acute ischemic stroke

The stress hyperglycemia ratio (SHR) is established as a reliable marker for assessing the severity of stress-induced hyperglycemia. While its effectiveness in managing patients with Acute Ischemic Stroke (AIS) remains to be fully understood. We aim to explore the relationship between SHR and clinical prognosis in AIS patients and to assess how diabetes status influences this relationship. In this study, we analyzed data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, selecting patients with AIS who required ICU admission. These patients were categorized into tertiles based on their SHR levels. We applied Cox hazard regression models and used restricted cubic spline (RCS) curves to investigate relationships between outcomes and SHR. The study enrolled a total of 2029 patients. Cox regression demonstrated that a strong correlation was found between increasing SHR levels and higher all-cause mortality. Patients in the higher two tertiles of SHR experienced significantly elevated 30-day and 90-day mortality rates compared to those in the lowest tertile. This pattern remained consistent regardless of diabetes status. Further, RCS analysis confirmed a progressively increasing risk of all-cause mortality with higher SHR levels. The findings indicate that SHR is association with increased 30-day and 90-day mortality among AIS patients, underscoring its potential value in risk stratification. Although the presence of diabetes may weaken this association, significant correlations persist in diabetic patients.

Evaluating the Impact of Nutritional Risk on Stress-Induced Hyperglycemia and Trauma Patient Outcomes.

Stress-induced hyperglycemia (SIH) and malnutrition are common in trauma patients and are linked to worse outcomes. This study examined the influence of nutritional status, determined by the Geriatric Nutritional Risk Index (GNRI), on the incidence of SIH in trauma patients. A retrospective analysis was conducted on adult trauma patients admitted to a Level I trauma center from 1 January 2009 to December 31, 2021. Patients were categorized into four groups: SIH, diabetic hyperglycemia (DH), diabetic normoglycemia (DN), and non-diabetic normoglycemia (NDN). Nutritional status was assessed using GNRI: high risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI ≤ 98), and no risk (GNRI > 98). Incidence of SIH and outcomes were analyzed across GNRI groups. SIH was associated with higher mortality across all GNRI groups compared to NDN, with the highest rate (45.7%) in the high-risk group. Mortality decreased as GNRI increased in all glucose groups. NDN patients had the lowest mortality rates across GNRI groups. There was no correlation between GNRI and SIH incidence (p = 0.259). SIH significantly influenced mortality across all nutritional status groups, with the highest impact in malnourished patients. Although malnutrition did not affect SIH incidence, both SIH and poor nutritional status independently contributed to worse trauma outcomes. Targeted management of hyperglycemia and nutritional deficiencies is crucial for improving survival.

The glycemic gap as a prognostic indicator in cardiogenic shock: a retrospective cohort study

BackgroundStress-induced hyperglycemia (SIH) is associated with poor outcomes in cardiogenic shock (CS), and there have been inconsistent results among patients with or without diabetes mellitus (DM). The glycemic gap (GG) is derived by subtracting A1c-derived average glucose from blood glucose levels; it is a superior indicator of SIH. We aimed to explore the role of GG in the outcomes of patients with CS.MethodsData on patients diagnosed with CS were extracted from the MIMIC-IV v2.0 database to investigate the relationship between GG and 30-day mortality (Number of absolute GG subjects = 359; Number of relative GG subjects = 357). CS patients from the Second Affiliated Hospital of Wenzhou Medical University were enrolled to explore the correlation between GG and lactic acid (Number of absolute GG subjects = 252; Number of relative GG subjects = 251). Multivariate analysis, propensity score-matched (PSM) analysis, inverse probability treatment weighting (IPTW), and Pearson correlation analysis were applied.ResultsAbsolute GG was associated with 30-day all-cause mortality in CS patients (HRadjusted: 1.779 95% CI: 1.137–2.783; HRPSM: 1.954 95% CI: 1.186–3.220; HRIPTW: 1.634 95% CI: 1.213–2.202). The higher the absolute GG level, the higher the lactic acid level (βadjusted: 1.448 95% CI: 0.474–2.423). A similar trend existed in relative GG (HRadjusted: 1.562 95% CI: 1.003–2.432; HRPSM: 1.790 95% CI: 1.127–2.845; HRIPTW: 1.740 95% CI: 1.287–2.352; βadjusted:1.294 95% CI: 0.369–2.219). Subgroup analysis showed that the relationship existed irrespective of DM. The area under the curve of GG combined with the Glasgow Coma Scale (GCS) for 30-day all-cause mortality was higher than that of GCS (absolute GG: 0.689 vs. 0.637; relative GG: 0.688 vs. 0.633). GG was positively related to the triglyceride-glucose index. Kaplan–Meier curves revealed that groups of higher GG with DM had the worst outcomes. The outcomes differed among races and GG levels (all P < 0.05).ConclusionsAmong patients with CS, absolute and relative GGs were associated with increased 30-day all-cause mortality, regardless of DM. The relationship was stable after multivariate Cox regression analysis, PSM, and IPTW analysis. Furthermore, they reflect the severity of CS to some extent. Hyperlactatemia and insulin resistance may underlie the relationship between stress-induced hyperglycemia and poor outcomes in CS patients. They both improve the predictive efficacy of the GCS.

Association of neutrophil extracellular traps burden with clinical and angiographic characteristics in patients with ST-elevation myocardial infarction

BackgroundThe precise triggers for atherosclerotic plaque rupture and the underlying pathophysiology of coronary thrombogenesis remain elusive. Polymorphonuclear neutrophils, particularly their formation of neutrophil extracellular traps (NETs), have garnered attention in the context of coronary atherothrombosis. This study sought to explore the association of NETs burden with clinical and angiographic characteristics in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI) and thrombus aspiration (TA). MethodsFor this study, 336 consecutive STEMI patients undergoing pPCI were considered for TA. Aspirated thrombi underwent histological analysis and NETs quantification via immunohistochemistry. Potential associations of clinical variables and angiographic outcomes with NETs burden were assessed. ResultsManual TA was selectively performed in 72 cases with increased thrombotic burden, and 60 thrombi were suitable for analysis and included in the current study. Most thrombi specimens displayed lytic features (63%), and almost three out of four were identified as white thrombi. Increased NETs burden was significantly associated with prolonged pain-to-balloon time (>300 min), OR = 10.29 (95% CI 2.11–42.22, p = 0.001), and stress-induced hyperglycemia OR = 6.58 (95% CI 1.23–52.63, p < 0.01) after multivariate regression analysis. Additionally, distal embolization, and left ventricular ejection fraction ≤40% were more frequent among patients with an elevated NETs burden OR = 16.9 (95% CI 4.23–44.52, p < 0.01) and OR = 3.2 (95% CI 1.05–12.1, p = 0.05), respectively. ConclusionElevated NETs burden in STEMI thrombi may be due to delayed reperfusion and stress-induced hyperglycemia, and it is associated with an increased risk of distal embolization and lower left ventricular ejection fraction. Further research is needed to elucidate the role of NETs as a potential therapeutic target in acute atherothrombosis.

Hyperglycemia in Orthopaedic Trauma Patients: Implications, Management, and Future Directions

Physiologic stress-induced hyperglycemia (SIH) significantly impacts patient outcomes in both non-diabetic and diabetic individuals following orthopaedic trauma. This review synthesizes current literature on SIH's effects, highlighting its association with increased surgical site infections (SSI), extended hospital stays, wound complications, nonunion, need for revision surgery, and mortality. Non-diabetic patients with SIH face worse outcomes compared to euglycemic patients, including a higher risk of deep infections and systemic complications. Diabetic patients experience exacerbated hyperglycemia during trauma, leading to poor wound healing and heightened infection risk. Effective glycemic control, through preoperative optimization, intraoperative monitoring, and postoperative management, is crucial for improving outcomes. Special considerations are discussed for the geriatric population, who are particularly vulnerable to SIH-induced morbidity and mortality. Future directions emphasize developing tailored glycemia management algorithms, utilizing continuous monitoring systems, and fostering multidisciplinary collaboration to optimize care for orthopaedic trauma patients.

Stress, Hyperglycemia, and Insulin Resistance Correlate With Neutrophil Activity and Impact Acute Myocardial Infarction Outcomes.

Introduction Acute insulin resistance (IR) and hyperglycemia are frequently observed during acute myocardial infarction (AMI), significantly influencing both immediate and long-term patient outcomes, irrespective of diabetic status. Neutrophilia and increased neutrophil activity, which are common in these scenarios, have been associated with poorer prognoses, as demonstrated in our recent findings. While it is well established that neutrophils and stress-induced hyperglycemia exacerbate inflammation and hinder recovery, the complex interplay between these factors and their combined impact on AMI prognosis remains inadequately understood. This study aims to investigate the effects of stress hyperglycemia and IR on AMI patients at the onset of the event and to elucidate the relationship between these metabolic disturbances and inflammatory markers, particularly neutrophils. Methods We conducted a longitudinal prospective study on 219 AMI patients at Elias Emergency Hospital in Bucharest, Romania, from April 2021 to September 2022. Patients were included within 24 hours of AMI with ST-segment elevation and excluded if they had acute infections or chronic inflammatory diseases. Blood samples were collected to study inflammatory biomarkers, including neutrophil extracellular traps (NETs), S100A8/A9, interleukin (IL)-1β, IL-18, and IL-6. Diabetic and pre-diabetic statuses were defined using glycated hemoglobin (HbA1c) and medical history (ADA 2019 criteria). To assess glycemic parameters, we employed the glycemia ratio (GR) and the homeostatic model assessment of insulin resistance (HOMA-IR) index, enabling a precise evaluation of stress hyperglycemia, acute IR, and their prognostic implications. Patients were stratified into groups based on GR calculations, categorized as under-average glycemia, normal glycemia, and stress hyperglycemia. Results The majority of patients in the stress hyperglycemia group exhibited an unfavorable prognosis. This group also demonstrated significantly elevated neutrophil counts and neutrophil-to-lymphocyte ratios (NLR). The GR was significantly and positively correlated with inflammation markers, including neutrophil count (Pearson's R = 0.181, P = 0.008) and NLR (Pearson's R = 0.318, P < 0.001), but showed no significant correlation with other evaluated inflammatory markers. Conclusions Our findings suggest that poor outcomes in AMI patients may be associated with stress hyperglycemia, as indicated by GR. AcuteIR, quantified by GR and HOMA-IR, exhibits a strong correlation with neutrophil count and NLR within the first 24 hours of AMI onset. However, no significant correlation was observed with other inflammatory markers, such as IL-1β, IL-18, and IL-6, underscoring the specific interplay between IR and neutrophil activity in this setting.

Effect of stress-induced hyperglycemia on long-term mortality in non-diabetic patients with acute type A aortic dissection: a retrospective analysis

Background Acute Type A Aortic Dissection (AAAD) is one of the most life-threatening diseases, often associated with transient hyperglycemia induced by acute physiological stress. The impact of stress-induced hyperglycemia on the prognosis of ST-segment elevation myocardial infarction has been reported. However, the relationship between stress-induced hyperglycemia and the prognosis of AAAD patients remains uncertain. Methods The clinical data of 456 patients with acute type A aortic dissection were retrospectively reviewed. Patients were divided into two groups based on their admission blood glucose. Cox model regression analysis was performed to assess the relationship between stress-induced hyperglycemia and the 30-day and 1-year mortality rates of these patients. Results Among the 456 patients, 149 cases (32.7%) had AAAD combined with stress-induced hyperglycemia (SIH). The results of the multifactor regression analysis of the Cox model indicated that hyperglycemia (RR = 1.505, 95% CI: 1.046–2.165, p = 0.028), aortic coarctation involving renal arteries (RR = 3.330, 95% CI: 2.237–4.957, p < 0.001), aortic coarctation involving superior mesenteric arteries (RR = 1.611, 95% CI: 1.056–2.455, p = 0.027), and aortic coarctation involving iliac arteries (RR = 2.034, 95% CI: 1.364–3.035, p = 0.001) were independent influences on 1-year postoperative mortality in AAAD patients. Conclusion The current findings indicate that stress-induced hyperglycemia measured on admission is strongly associated with 1-year mortality in patients with AAAD. Furthermore, stress-induced hyperglycemia may be related to the severity of the condition in patients with AAAD.

Review Article - Diabetes Technology in the Hospital: An Update.

There have been many developments in diabetes technology in recent years, with continuous glucose monitoring (CGM), insulin pump therapy (CSII) and automated insulin delivery (AID) becoming progressively accepted in outpatient diabetes care. However, the use of such advanced diabetes technology in the inpatient setting is still limited for several reasons, including logistical challenges and staff training needs. On the other hand, hospital settings with altered diet and stress-induced hyperglycemia often pose challenges to tight glycemic control using conventional treatment tools. Integrating smarter glucose monitoring and insulin delivery devices into the increasingly technical hospital environment could reduce diabetes-related morbidity and mortality. This narrative review describes the most recent literature on the use of diabetes technology in the hospital and suggests avenues for further research. Advanced diabetes technology has the potential to improve glycemic control in hospitalized people with and without diabetes, and could add particular value in certain conditions, such as nutrition therapy or perioperative management. Taken together, CGM allows for more accurate and patient-friendly follow-up and ad hoc titration of therapy. AID may also provide benefits, including improved glycemic control and reduced nursing workload. Before advanced diabetes technology can be used on a large scale in the hospital, further research is needed on efficacy, accuracy and safety, while implementation factors such as cost and staff training must also be overcome.

Palliative effect of abalone insulin-related peptide 2 on emersion stress-induced hyperglycemia in the Pacific abalone (Haliotis discus hannai)

The Pacific abalone (Haliotis discus hannai), an economically important marine mollusk in East Asia, is often exposed to extreme environments, such as high water temperatures during summer and air exposure during handling or transportation. These stressful conditions lead to hyperglycemia and the generation of reactive oxygen species (ROS), resulting in oxidative stress and subsequent cell damage in the organism. To understand the role of insulin-related peptides in the regulation of elevated hemolymph glucose, hyperglycemia was confirmed in abalone under high water temperature and air (emersion) exposure (p < 0.05). To prove the existence of a glucose regulatory system in abalone, changes in hemolymph glucose were measured after bovine insulin injection, and hemolymph glucose was lowered by bovine insulin injection in hyperglycemia caused by both stressors (p < 0.05), supporting the existence of a glucose regulatory system functionally similar to that of vertebrates. Among the three abalone insulin-related peptides (AIPs), which were previously reported to be upregulated along with hemolymph glucose levels upon feeding, the relative mRNA expression of AIP2 in the cerebral ganglion showed a close correlation with high water temperature and emersion stress, which peaked 12 h after treatment (p < 0.05). Based on these results, we focused on the function of AIP2 in glucose homeostasis and characterized the localization of AIP2 mRNA-expressing cells in the cerebral ganglion using in situ hybridization. Positive signals from RNA probes were detected in neural cortex cells in the cerebral ganglion. Furthermore, suppressing AIP2 mRNA expression using RNA interference with double-stranded RNA (dsRNA) revealed that dsRNA-AIP2 injected abalone maintained high hemolymph glucose levels after 24 h of recovery following 1 h of emersion stress (p < 0.01). In contrast, abalones that received dsRNA-GFP and molluscan saline showed relatively rapid clearance of hemolymph glucose. This study demonstrates that AIP2 gene expression affects the recovery rate from emersion stress-induced hyperglycemia by regulating hemolymph glucose.

Model predictive control of blood glucose in critically ill patients using Gaussian processes

Abstract Stress-induced hyperglycemia and high glycemic variability are common in intensive care patients. Several clinical studies show the benefits of tight blood glucose control, including lower mortality. This article presents an algorithm for blood glucose control in the intensive care unit. An Unscented Kalman Filter is developed to estimate the glucose metabolism state and time-varying insulin sensitivity from blood glucose measurements. Gaussian Processes are used to predict future insulin sensitivity changes based on previous measurements. A model predictive controller is designed to estimate optimal insulin infusion based on current state, predicted insulin sensitivity and planned nutrition. The developed control algorithm allows individualized blood glucose control with reduced glycemic variability and reduced risk of hypoglycemia in the intensive care unit.

The Effect of HIV on the Association of Hyperglycaemia and Active Tuberculosis in Zambia, a Case–Control Study

ObjectivesTo determine if HIV modifies the association between hyperglycaemia and active tuberculosis in Lusaka, Zambia.MethodsA case–control study among newly—diagnosed adult tuberculosis cases and population controls in three areas of Lusaka. Hyperglycaemia is determined by random blood glucose (RBG) concentration measured at the time of recruitment; active tuberculosis disease by clinical diagnosis, and HIV status by serological result. Multivariable logistic regression is used to explore the primary association and effect modification by HIV.ResultsThe prevalence of RBG concentration ≥ 11.1 mmol/L among 3843 tuberculosis cases was 1.4% and among 6977 controls was 1.5%. Overall, the adjusted odds ratio of active tuberculosis was 1.60 (95% CI 0.91–2.82) comparing those with RBG concentration ≥ 11.1– < 11.1 mmol/L. The corresponding adjusted odds ratio among those with and without HIV was 5.47 (95% CI 1.29–23.21) and 1.17 (95% CI 0.61–2.27) respectively; p-value for effect modification by HIV = 0.042. On subgroup analysis, the adjusted odds ratio of smear/Xpert-positive tuberculosis was 2.97 (95% CI 1.49–5.90) comparing RBG concentration ≥ 11.1– < 11.1 mmol/L.ConclusionsOverall, no evidence of association between hyperglycaemia and active tuberculosis was found, though among those with HIV and/or smear/Xpert-positive tuberculosis there was evidence of association. Differentiation of hyperglycaemia caused by diabetes mellitus and stress-induced hyperglycaemia secondary to tuberculosis infection is important for a better understanding of these findings.

Нарушения углеводного обмена у пациентов с боевыми травмами

Aim. To investigate the prevalence and some aspects of the carbohydrate metabolism pathology in patients with combat limb injuries. Materials and methods. 210 patients who suffered from combat injuries of the lower and/or upper extremities from 4 to 58 days (mean 15.9±8.7 days) before admission to the hospital were enrolled in the study. All study participants were men. The mean age of the patients was 36.0±8.4 years (19–59 years). Fasting venous blood glucose concentrations were determined in all patients. Patients with hyperglycemia underwent a study of the glycemic profile and HbA1c. Stress-induced hyperglycemia, estimated mean glucose level over the past 3 months (ADAG), and glycemic gap were calculated. Insulin in fasting blood plasma was determined and the HOMA-IR insulin resistance index was calculated. Results. The incidence of hyperglycemia was 23.3%. In the general group of patients, the mean glucose concentration was 5.5±1.0 mmol/l (3.1–9.73 mmol/l). In the group of patients with hyperglycemia, the mean blood glucose level reached 6.7±0.9 mmol/l, in patients with normal glucose concentration – 5.1±0.5 mmol/l (p&lt;0.000001). The mean fasting blood glucose concentration in patients aged 40 years and older reached 5.7±1.1 mmol/l, those under 40 years old – 5.2±0.8 mmol/l (p=0.005). A significant direct correlation was registered between the fasting glucose level upon admission to the hospital and the age of the patients (r=0.26; p=0.00003). The relative risk of hyperglycemia in patients aged 40 years and older was 1.84 (confidence interval 1.005–3.37; p=0.01). The mean time elapsed since injury in patients with hyperglycemia reached 13.2±5.7 days, with normal glucose concentration – 16.7±9.2 days (p=0.02). Patients with hyperglycemia had lower levels of total protein (58.3±10.2 and 62.1±6.9 g/l, respectively; p=0.004), albumin (31.2±4.6 and 33.2±4.9 g/l; p=0.04), hemoglobin (97.7±18.9 and 105.9±16.9 g/l; p=0.004), but higher levels of C-reactive protein (61.0±55.4 and 32.9±38.1 mg/l; p=0.0001), leukocytes (10.6±4.4 and 9.3±3.4×109/l; p=0.02), count of neutrophils (7.8±4.3 and 6.4±2.9×109/l; p=0.01), proportion of neutrophils (71.6±9.6% and 67.7±7.7%; p=0.004), as well as fibrinogen concentration (5.7±1.4 and 4.8±1.2 g/l; p=0.0002) than patients with normal blood glucose levels. In patients with hyperglycemia, the mean HbA1c level was 5.3±0.6%, stress-induced hyperglycemia – 1.4±0.2 mmol/l. The median glycemic gap reached 1.51 mmol/l (Q1–Q3: 0.88–2.1 mmol/l). The median insulin concentration was 12.9 µIU/ml (Q1–Q3: 9.2–27.0 µIU/ml), the insulin resistance index was 3.3 (Q1–Q3: 2.1–8.8). The mean fasting blood glucose concentration at the last determination in patients with initial hyperglycemia reached 5.8±1.3 mmol/l. During observation, in 64.6% of the patients with hyperglycemia upon admission, glucose levels returned to normal, while in 35.4% mild hyperglycemia remained. The median time to normalization of fasting blood glucose concentration or to the last determination of this indicator was 17.5 days (Q1–Q3: 8–30 days). Conclusions. The study results indicate a frequent detection of hyperglycemia in patients with combat limb injuries. In most cases the increase in fasting glucose levels is small and in most patients this indicator returns to normal within a relatively short time. It is necessary to continue research of stress-induced hyperglycemia in the patients with combat injuries and to elucidate the pathogenetic basis of this pathology.

Comparison of stress hyperglycemia ratio and glycemic gap on acute ICH in-hospital outcomes.

To compare the effect of different indicators on stress-induced hyperglycemia for predicting in-hospital outcomes of acute intracerebral hemorrhage. Using data from the Chinese Stroke Center Alliance database, which is a national, multicenter, prospective, and consecutive program. Stress-induced hyperglycemia was described as glycemic gap (GG, defined as fasting blood glucose [FBG] minus estimated average blood glucose) and stress hyperglycemia ratio (SHR, defined as FBG-to-estimated average blood glucose ratio [SHR 1] or FBG-to-HbA1c ratio [SHR 2]). The primary outcome was in-hospital mortality, and the second outcome was hematoma expansion. A total of 71,333 patients with acute intracerebral hemorrhage were included. In multivariate analyses, the highest levels of GG (OR 1.68, 95% CI 1.12-2.51), SHR 1 (OR 1.73, 95% CI 1.15-2.60), and SHR 2 (OR 2.07, 95% CI 1.33-3.23) were associated with in-hospital death (all the p trends <0.01). Only the highest level of SHR 2 (OR 1.24 [1.02-1.51], p trend >0.05) was related to hematoma expansion. No association between GG or SHR 1 and hematoma expansion was observed. The areas under the ROC curve of GG, SHR 1, and SHR 2 for in-hospital mortality were 0.8808 (95% CI 0.8603-0.9014), 0.8796 (95% CI 0.8589-0.9002), and 0.8806 (95% CI 0.8600-0.9012). The areas under the ROC curve of SHR 2 for hematoma expansion were 0.7133 (95% CI 0.6964-0.7302). SHR (FBG-to-HbA1c ratio) was associated with both in-hospital death and hematoma expansion in intracerebral hemorrhage, and might serve as an accessory indicator for the in-hospital prognosis of intracerebral hemorrhage.