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Background: Stress-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., Methods: Data 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., Results: Absolute GG was associated with 30-day all-cause mortality in CS patients (HR adjusted : 1.779 95% CI: 1.137-2.783; HR PSM : 1.954 95% CI: 1.186-3.220; HR IPTW : 1.634 95% CI: 1.213-2.202). The higher the absolute GG level, the higher the lactic acid level (β adjusted : 1.448 95% CI: 0.474-2.423). A similar trend existed in relative GG (HR adjusted : 1.562 95% CI: 1.003-2.432; HR PSM : 1.790 95% CI: 1.127-2.845; HR IPTW : 1.740 95% CI: 1.287-2.352; β adjusted :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)., Conclusions: Among 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., (© 2024. The Author(s).)

Aim: This study was designed to investigate the association between Charlson Comorbidity Index (CCI) and in-hospital mortality and other clinical outcomes among patients with hyperglycemic crises., Method: This retrospective cohort study was conducted using data from electric medical records. A total of 1668 diabetic patients with hyperglycemic crises from six tertiary hospitals met the inclusion criteria. CCI < 4 was defined as low CCI and CCI ≥ 4 was defined as high CCI. Propensity score matching (PSM) with the 1:1 nearest neighbour matching method and the caliper value of 0.02 was used to match the baseline characteristics of patients with high CCI and low CCI to reduce the confounding bias. In-hospital mortality, ICU admission, hypoglycemia, hypokalemia, acute kidney injury, length of stay (LOS), and hospitalisation expense between low CCI and high CCI were compared and assessed. Univariate and multivariate regression were applied to estimate the impact of CCI on in-hospital and other clinical outcomes., Outcome: One hundred twenty-one hyperglycemic crisis (HC) patients died with a mortality rate of 7.3%. After PSM, compared with low CCI, patients with high CCI suffered higher in-hospital mortality, ICU admission, LOS, and hospitalisation expenses. After multivariate regression, age (aOR: 1.12, 95% confidence interval [CI]: 1.06-1.18, p < 0.001), CCI(aOR: 4.42, 95% CI: 1.56-12.53, p = 0.005), uninsured (aOR: 22.32, 95% CI: 4.26-116.94, p < 0.001), shock (aOR: 10.57, 95% CI: 1.41-79.09, p = 0.022), mechanical ventilation (aOR: 75.29, 95% CI: 12.37-458.28, p < 0.001), and hypertension (aOR: 4.34, 95% CI: 1.37-13.82, p = 0.013) were independent risk factors of in-hospital mortality of HC patients. Besides, high CCI was an independent risk factor for higher ICU Admission (aOR: 5.91, 95% CI: 2.31-15.08, p < 0.001), hypoglycemia (aOR: 2.19, 95% CI:1.01-4.08, p = 0.049), longer LOS (aOR: 1.23, 95% CI: 1.19-2.27, p = 0.021), and higher hospitalisation expense (aOR: 2089.97, 95% CI: 193.33-3988.61, p = 0.031) of HC patients., Conclusion: CCI is associated with in-hospital mortality, ICU admission, hypoglycemia, LOS, and hospitalisation expense of HC patients. CCI could be an ideal indicator to identify, monitor, and manage chronic comorbidities among HC patients., (© 2024 John Wiley & Sons Ltd.)

Objectives: Relative dysglycemia has been proposed as a clinical entity among critically ill patients in the ICU, but is not well studied. This study aimed to clarify associations of relative hyperglycemia and hypoglycemia during the first 24 hours after ICU admission with in-hospital mortality and the respective thresholds., Design: A single-center retrospective study., Setting: An urban tertiary hospital ICU., Patients: Adult critically ill patients admitted urgently between January 2016 and March 2022., Interventions: None., Measurements and Main Results: Maximum and minimum glycemic ratio (GR) was defined as maximum and minimum blood glucose values during the first 24 hours after ICU admission divided by hemoglobin A1c-derived average glucose, respectively. Of 1700 patients included, in-hospital mortality was 16.9%. Nonsurvivors had a higher maximum GR, with no significant difference in minimum GR. Maximum GR during the first 24 hours after ICU admission showed a J-shaped association with in-hospital mortality, and a mortality trough at a maximum GR of approximately 1.12; threshold for increased adjusted odds ratio for mortality was 1.25. Minimum GR during the first 24 hours after ICU admission showed a U-shaped relationship with in-hospital mortality and a mortality trough at a minimum GR of approximately 0.81 with a lower threshold for increased adjusted odds ratio for mortality at 0.69., Conclusions: Mortality significantly increased when GR during the first 24 hours after ICU admission deviated from between 0.69 and 1.25. Further evaluation will necessarily validate the superiority of personalized glycemic management over conventional management., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002-1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population., (© 2024. The Author(s).)

Background: Community-acquired pneumonia (CAP) is a significant health issue among the elderly, with severe cases (SCAP) having high mortality rates. This study assesses the predictive significance of the stress hyperglycemia ratio (SHR) in elderly SCAP patients and its impact on outcomes in both diabetic and non-diabetic patients., Methods and Materials: This retrospective study included 406 SCAP patients aged 65 or older from the Second People's Hospital of Lianyungang (January 2020 to December 2023). Data collected included demographics, medical history, vital signs, and lab results. SHR was calculated from initial blood glucose and estimated average glucose (HbA1c). Statistical analyses, including Cox regression and Kaplan-Meier analysis, evaluated SHR's impact on mortality. Mediation models explored the effects of neutrophil-lymphocyte ratio (NLR) and SHR., Results: The 28-day mortality rate was 21.67%. Deceased patients had higher age, Charlson Comorbidity Index, procalcitonin, NLR, glucose, and SHR levels compared to survivors (P < 0.05). Both SHR and NLR significantly increased mortality risk, particularly in non-diabetic patients. Combining NLR and SHR improved ROC AUC to 0.898, with 89.80% sensitivity and 81.10% specificity. Kaplan-Meier analysis showed higher cumulative survival for SHR < 1.14, regardless of diabetes status (P < 0.05). NLR mediated 13.02% of the SHR-survival relationship, while SHR mediated 14.06% of the NLR-survival relationship., Conclusion: Elevated SHR is a significant mortality risk factor in elderly SCAP patients, independent of diabetes status. Stringent glucose control and careful monitoring of SHR may improve outcomes in elderly patients with acute respiratory conditions., (© 2024. The Author(s).)

Aims: In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes., Methods: We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes., Results: Time in range (3.9-10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7-5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9-29.5], and 2.4 %-points [95 % CI 0.3-4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06-1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07-1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission., Conclusions: Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status., Competing Interests: Declaration of competing interest MTO, CKK, and KBH have nothing to disclose. UPB has served on advisory boards and received lecture fees from Novo Nordisk and Sanofi. PLK has received speaker fees from Sanofi, Boehringer Ingelheim, Novo Nordisk, and AstraZeneca., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Whether intensive glucose control reduces mortality in critically ill patients remains uncertain. Patient-level meta-analyses can provide more precise estimates of treatment effects than are currently available., Methods: We pooled individual patient data from randomized trials investigating intensive glucose control in critically ill adults. The primary outcome was in-hospital mortality. Secondary outcomes included survival to 90 days and time to live cessation of treatment with vasopressors or inotropes, mechanical ventilation, and newly commenced renal replacement. Severe hypoglycemia was a safety outcome., Results: Of 38 eligible trials (n=29,537 participants), 20 (n=14,171 participants) provided individual patient data including in-hospital mortality status for 7059 and 7049 participants allocated to intensive and conventional glucose control, respectively. Of these 1930 (27.3%) and 1891 (26.8%) individuals assigned to intensive and conventional control, respectively, died (risk ratio, 1.02; 95% confidence interval [CI], 0.96 to 1.07; P=0.52; moderate certainty). There was no apparent heterogeneity of treatment effect on in-hospital mortality in any examined subgroups. Intensive glucose control increased the risk of severe hypoglycemia (risk ratio, 3.38; 95% CI, 2.99 to 3.83; P<0.0001)., Conclusions: Intensive glucose control was not associated with reduced mortality risk but increased the risk of severe hypoglycemia. We did not identify a subgroup of patients in whom intensive glucose control was beneficial. (Funded by the Australian National Health and Medical Research Council and others; PROSPERO number CRD42021278869.).

Prior research has demonstrated that erectile dysfunction (ED) is a significant risk factor for cardiovascular disease (CVD) and premature mortality. Few studies have examined the link between ED and hyperglycemia, and the predictive power of ED for mortality in individuals with hyperglycemia. A cohort of 1584 adults diagnosed with hyperglycemia, consisting of 583 individuals with diabetes and 1001 individuals with prediabetes, was selected from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. The study found a positive correlation between severe ED and hyperglycemia (OR, 2.03; 95% CI 1.53-2.68), while no significant relationship was observed between severe ED and CVD events (OR, 1.60; 95% CI 0.91-2.80). Additionally, no statistical association was found between diabetes or prediabetes status and ED. After multivariable adjustments, severe ED was found to be significantly associated with an increased risk of all-cause mortality (HR, 1.67; 95% CI 1.16-2.39), while no significant association was observed between severe ED and CVD mortality (HR, 1.92; 95% CI 0.92-3.98). Our study indicates a significant correlation between ED and hyperglycemia status. Hyperglycemia Individuals with ED generally exhibited an unfavorable prognosis for mortality due to all causes and CVD, particularly among those with low levels of physical activity., (© 2024. The Author(s).)

Background: Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain., Methods: We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999-2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors., Results: In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value < 0.05). The threshold value for HbA1c was 5.4%, and the HRs (95% CI) below and above the threshold value were 0.917 (0.856,0.983) and 1.026 (1.010,1.043), respectively. Similar associations were found between fasting glucose and all-cause mortality in cancer survivors, and the threshold value was 5.7 mmol/L., Conclusions: HbA1c was nonlinearly associated with all-cause mortality in cancer survivors, and the critical value of HbA1c in decreased mortality was 5.4%, suggesting optimal glucose management in cancer survivors may be a key to preventing premature death in cancer survivors., (© 2024. The Author(s).)

Both of neurological emergencies and hyperglycemia are independently associated risk factors of mortality in the ICU patients. In critically ills, hyperglycemia is secondary to already existing DM or stress-induced hyperglycemia (SIH). Admission glycemic gap (AGG) is considered as a reliable indicator of SIH. This study aimed to explore the association of AGG on diabetic neuro-critical patients' short-term mortality, and understand the potential of AGG as the predictor of outcome. Sixty adult diabetic neuro-critical patients admitted in ICU and stayed at least for 24 hours, were prospectively observed for 30 days, or until discharge or death, whichever came first. The patients' initial clinical assessment and HbA1c, CBC, ABG, and blood glucose level were done within 24 hours of admission. A1c derived admission glucose (ADAG) was calculated as, ADAG = (1.59 × HbA1c) - 2.59 (mmol/L). The AGG was calculated by subtracting ADAG from admission blood glucose level (ABGL). Death or survival of 30 days was our primary outcome and participants were divided between survivor or non-survivor groups according to primary outcome. Statistical comparisons of the study variables between the groups were performed and the relationship between parameters derived from blood glucose and mortality was prospected. Among the 60 patients enrolled, 35(58.3%) were non-survivors and 25(41.7%) were survivors. Age, sex, residence, primary diagnosis, co-morbidity, or drug history had no association with survival/non-survival. Among the initial clinical assessment parameters, lower GCS had significant association with non-survival. AGG, HbA1c, ADAG and ABGL were significantly different between the groups, with higher values in the non-survivors. Lower GCS, and higher AGG, HbA1c, ADAG and ABGL showed significant odds of non-survival. The highest odds of non- survival was for AGG (OR 2.95, 95% CI: 1.83-4.75; p<0.001). For ABGL and HbA1c the OR were 2.03 (95% CI: 1.44-2.86; p<0.001) and 1.93 (95% CI: 1.04-3.58; p<0.04) respectively. The final adjusted odds (aOR) of non-survival for higher AGG was 3.25 (95% CI: 1.71-6.16; p<0.001), signifying that AGG is independently associated with non-survival. AGG, GCS level, ABGL, HbA1c level, and ADAG can predict short-term outcome (mortality). However, AGG has the greatest potential to predict short-term outcome in diabetic neuro-critical patients.

Aims/introduction: Mean blood glucose (MBG) level is associated with mortality among critically ill patients. We undertook a cohort study to investigate the relationship between MBG and mortality in critically ill patients., Materials and Methods: Critically ill patients were enrolled from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. MBG was calculated to represent the overall glycemic status during intensive care unit (ICU) hospitalization, and a multivariate logistic regression determined the relationship between MBG and ICU mortality in different subgroups of critically ill patients., Results: A total of 8,973 patients were included in the study, 1,244 of whom died within 28 days, including 5,402 men and 3,571 women. Multivariate adjusted restricted cubic spline analyses suggested that the relationship between MBG and ICU mortality was a "J" shape. Logistic regression showed 28 day mortality in group 3 (glucose ≥10 mmol/L): the adjusted odds ratio was 2.06 (95% confidence interval 1.65-2.57). The results of subgroup analysis showed that hyperglycemia had a more significant impact on ICU mortality in patients without diabetes, hypoglycemia and liver disease, and the ICU mortality risk of non-diabetes patients was always higher than that of diabetes patients with the same hyperglycemia level., Conclusions: Current evidence suggested a J-shaped relationship between MBG and mortality in critically ill patients., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/hypothesis: Continuous glucose monitoring (CGM) provides comprehensive information on the exposure to dysglycaemia. This study aimed to investigate the threshold of hyperglycaemia related to mortality risk in critically ill patients using CGM technology., Methods: A total of 293 adult critically ill patients admitted to intensive care units of five medical centres were prospectively included between May 2020 and November 2021. Participants wore intermittently scanned CGM for a median of 12.0 days. The relationships between different predefined time above ranges (TARs), with the thresholds of hyperglycaemia ranging from 7.8 to 13.9 mmol/l (140-250 mg/dl), and in-hospital mortality risk were assessed by multivariate Cox proportional regression analysis. Time in ranges (TIRs) of 3.9 mmol/l (70 mg/dl) to the predefined hyperglycaemic thresholds were also assessed., Results: Overall, 66 (22.5%) in-hospital deaths were identified. Only TARs with a threshold of 10.5 mmol/l (190 mg/dl) or above were significantly associated with the risk of in-hospital mortality, after adjustment for covariates. Furthermore, as the thresholds for TAR increased from 10.5 mmol/l to 13.9 mmol/l (190 mg/dl to 250 mg/dl), the hazards of in-hospital mortality increased incrementally with every 10% increase in TARs. Similar results were observed concerning the associations between TIRs with various upper thresholds and in-hospital mortality risk. For per absolute 10% decrease in TIR 3.9-10.5 mmol/l (70-190 mg/dl), the risk of in-hospital mortality was increased by 12.1% (HR 1.121 [95% CI 1.003, 1.253])., Conclusions/interpretation: A glucose level exceeding 10.5 mmol/l (190 mg/dl) was significantly associated with higher risk of in-hospital mortality in critically ill patients., (© 2024. The Author(s).)

Aims: Hyperglycemia on admission is associated with poor prognosis in ischemic stroke (IS) patients. We aimed to investigate the relationship between stress hyperglycemia ratio (SHR) and short-term or long-term mortality in IS patients in the ICU and to explore whether this relationship is influenced by diabetes status., Materials and Methods: We collected patients with severe IS requiring ICU admission in the Medical Information Mart for Intensive Care (MIMIC-IV) database and calculated SHR. Outcomes included 30-day, 90-day, and 1-year mortality. The association between SHR and mortality in patients with critical IS was elucidated using Multivariate Cox regression and subgroup analysis for diabetes., Results: A total of 1376 patients were recruited. After adjusting for potential confounders, patients in the third and fourth quartiles had a significantly increased risk of death at 30 days, 90 days, and 1 year compared to the first quartile of SHR (Q3 vs. Q1: HR 1.56-1.80, all p < 0.02; Q4 vs. Q1: HR 1.75-2.15, all p < 0.001; all p for trend < 0.001). In addition, the highest quartile of SHR was significantly associated with short-term or long-term mortality compared with the first quartile, regardless of diabetes status., Conclusions: Our results suggest that stress hyperglycemia, defined by the glucose/HbA1c ratio, is associated with increased short-term and long-term mortality in patients with ischemic stroke, independent of the patient's diabetes status., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

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.

Introduction: We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission., Research Design and Methods: Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student's t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X 2 test was used for categorical variable., Results: Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0-14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely., Conclusions: Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes., Competing Interests: Competing interests: DCS is a stockholder/shareholder of GI Windows (not related to current study). MEM participated in clinical trials, through her institution sponsored by DexCom Inc. JM was a consultant for Novo Nordisk and Eli Lilly and is an employee of Sequel. GG participated in clinical trials, through her institution, sponsored by Spruce Bioscience and Sparrow Pharmaceuticals. NEP participated in a clinical trial through her institution sponsored by Dexcom Inc. RSW participated in clinical trials, through her institution, sponsored by Insulet, Tandem, Eli Lilly, Novo Nordisk, Amgen, Diasome and Mannkind. DexCom Inc. provided devices, at reduced cost, for research studies., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Elevated plasma glucose levels are common in patients suffering acute ischemic stroke (AIS), and acute hyperglycemia has been defined as an independent determinant of adverse outcomes. The impact of acute-to-chronic glycemic ratio (ACR) has been analyzed in other diseases, but its impact on AIS prognosis remains unclear. The main aim of this study was to assess whether the ACR was associated with a 3-month poor prognosis in patients with AIS., Research, Design and Methods: Retrospective analysis of patients admitted for AIS in Hospital del Mar, Barcelona. To estimate the chronic glucose levels (CGL) we used the formula eCGL= [28.7xHbA1c (%)]-46.7. The ACR (glycemic at admission / eCGL) was calculated for all subjects. Tertile 1 was defined as: 0.28-0.92, tertile 2: 0.92-1.13 and tertile 3: > 1.13. Poor prognosis at 3 months after stroke was defined as mRS score 3-6., Results: 2.774 subjects with AIS diagnosis were included. Age, presence of diabetes, previous disability (mRS), initial severity (NIHSS) and revascularization therapy were associated with poor prognosis (p values < 0.05). For each 0.1 increase in ACR, there was a 7% increase in the risk of presenting a poor outcome. The 3rd ACR tertile was independently associated with a poor prognosis and mortality. In the ROC curves, adding the ACR variable to the classical clinical model did not increase the prediction of AIS prognosis (0.786 vs. 0.781)., Conclusions: ACR was positively associated with a poor prognosis and mortality at 3-months follow-up after AIS. Subjects included in the 3rd ACR tertile presented a higher risk of poor prognosis and mortality. Baseline glucose or ACR did not add predictive value in comparison to only using classical clinical variables., (© 2024. The Author(s).)

Background and Importance: Lactate is an already recognized biomarker for short-term mortality. However, how glycemia and diabetes affect the predictive ability of lactate needs to be revealed., Objective: To determine how hypoglycemia, normoglycemia, and hyperglycemia modify the predictive ability of lactate for short-term mortality (3 days). The secondary objective was to evaluate the predictive ability of lactate in diabetic patients., Design, Settings and Participants: Prospective, observational study performed between 26 October 2018 and 31 December 2022. Multicenter, EMS-delivery, ambulance-based study, considering 38 basic life support units and 5 advanced life support units referring to four tertiary care hospitals (Spain). Eligible patients were adults recruited from among all phone requests for emergency assistance who were later evacuated to emergency departments., Outcomes Measure and Analysis: The primary outcome was in-hospital mortality from any cause within the third day following EMS attendance. The main predictors considered were lactate, blood glucose levels and previous diabetes., Main Results: A total of 6341 participants fulfilled the inclusion criteria. 68 years (IQR: 51-80); 41.4% were female. The 3-day in-hospital mortality rate was 3.5%. The predictive capacity of lactate for 3-day mortality was only significantly different between normo-glycemia and hyperglycemia. The best predictive result was for normo-glycemia - AUC = 0.897 (95% CI: 0.881-0.913) - then hyperglycemia - AUC = 0.819 (95% CI: 0.770-0.868) and finally, hypoglycemia - AUC = 0.703 (95% CI: 0.422-0.983). The stratification according to diabetes presented no statistically significant difference, and the predictive results were AUC = 0.924 (95% CI: 0.892-0.956), AUC = 0.906 (95% CI: 0.884-0.928), and AUC = 0.872 (95% CI: 0.817-0.927) for nondiabetes, uncomplicated cases, and end-organ damage diabetes, respectively., Conclusion: Our results demonstrated that glycemia, but not diabetes, alters the predictive ability of lactate. Therefore, hyperglycemia should be considered when interpreting lactate, since this could improve screening to detect cryptic shock conditions., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population., Methods: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted., Results: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis., Conclusions: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped., (© 2024 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear., Methods: 10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)-2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI)., Results: During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58-2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08-2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42-2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination., Conclusions: SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status., (© 2024. The Author(s).)

Background: Stress hyperglycemia ratio (SHR) has shown a predominant correlation with transient adverse events in critically ill patients. However, there remains a gap in comprehensive research regarding the association between SHR and mortality among patients experiencing cardiac arrest and admitted to the intensive care unit (ICU)., Methods: A total of 535 patients with their initial ICU admission suffered cardiac arrest, according to the American Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients were stratified into four categories based on quantiles of SHR. Multivariable Cox regression models were used to evaluate the association SHR and mortality. The association between SHR and mortality was assessed using multivariable Cox regression models. Subgroup analyses were conducted to determine whether SHR influenced ICU, 1-year, and long-term all-cause mortality in subgroups stratified according to diabetes status., Results: Patients with higher SHR, when compared to the reference quartile 1 group, exhibited a greater risk of ICU mortality (adjusted hazard ratio [aHR] = 3.029; 95% CI: 1.802-5.090), 1-year mortality (aHR = 3.057; 95% CI: 1.885-4.958), and long-term mortality (aHR = 3.183; 95% CI: 2.020-5.015). This association was particularly noteworthy among patients without diabetes, as indicated by subgroup analysis., Conclusion: Elevated SHR was notably associated with heightened risks of ICU, 1-year, and long-term all-cause mortality among cardiac arrest patients. These findings underscore the importance of considering SHR as a potential prognostic factor in the critical care management of cardiac arrest patients, warranting further investigation and clinical attention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lian, Xue, Lu and Zheng.)

Objective: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related., Research Design and Methods: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC., Results: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10 - 20 ); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13))., Conclusions: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation., (© 2024. The Author(s).)

Background: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis., Methods: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms., Results: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322)., Conclusion: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis., (© 2024. The Author(s).)

Objective: The purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States., Methods: This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted., Results: The RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (β:-0.76, P<0.05) and Digit Symbol Substitution tests (β:-5.02, P<0.05). Nevertheless, these results showed marginal significance in Total Word Recall test as well as Animal Fluency test. Among all subgroup analyses performed, participants with both abnormal SII levels and diabetes exhibited the greatest decline in cognitive function compared to those with only diabetes. Furthermore, KM curve demonstrated that the combination of abnormal SII levels and diabetes decreased survival rate among participants., Conclusion: The findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Risk assessment for triple-vessel disease (TVD) remain challenging. Stress hyperglycemia represents the regulation of glucose metabolism in response to stress, and stress hyperglycemia ratio (SHR) is recently found to reflect true acute hyperglycemic status. This study aimed to evaluate the prognostic value of SHR and its role in risk stratification in TVD patients with acute coronary syndrome (ACS)., Methods: A total of 3812 TVD patients with ACS with available baseline SHR measurement were enrolled from two independent centers. The endpoint was cardiovascular mortality. Cox regression was used to evaluate the association between SHR and cardiovascular mortality. The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) II (SSII) was used as the reference model in the model improvement analysis., Results: During a median follow-up of 5.1 years, 219 (5.8%) TVD patients with ACS suffered cardiovascular mortality. TVD patients with ACS with high SHR had an increased risk of cardiovascular mortality after robust adjustment for confounding (high vs. median SHR: adjusted hazard ratio 1.809, 95% confidence interval 1.160-2.822, P = 0.009), which was fitted as a J-shaped pattern. The prognostic value of the SHR was found exclusively among patients with diabetes instead of those without diabetes. Moreover, addition of SHR improved the reclassification abilities of the SSII model for predicting cardiovascular mortality in TVD patients with ACS., Conclusions: The high level of SHR is associated with the long-term risk of cardiovascular mortality in TVD patients with ACS, and is confirmed to have incremental prediction value beyond standard SSII. Assessment of SHR may help to improve the risk stratification strategy in TVD patients who are under acute stress., (© 2024. The Author(s).)

Objectives: The aim of this study was to determine the associations between glucocorticoid administration during chemotherapy for hematologic malignancy and hyperglycemia, new-onset diabetes, and mortality in Ontario, Canada. Hospitalization and emergency room utilization during the chemotherapy treatment period were also described., Methods: We conducted a retrospective cohort study using health administrative data from ICES, Ontario, to assess risk of new-onset diabetes, new-onset hyperglycemia, and hyperglycemia for individuals with leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL) receiving glucocorticoids during chemotherapy between 2006 and 2016. Using multivariable regression models, we determined the associations between glucocorticoid exposure and our outcomes of interest, controlling for age, sex, marginalization, and comorbidities., Results: Our cohort included 19,530 individuals; 71.1% (n=13,893) received a glucocorticoid. The highest proportion of hyperglycemia occurred with leukemia (25.4%, n=1,301). Of the 15,580 individuals with no history of diabetes, those with leukemia had the highest rate of new-onset diabetes (7.1%, n=279) and new-onset hyperglycemia (18.1%, n=641), and glucocorticoid exposure increased the risk of new-onset diabetes (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p=0.04) and new-onset hyperglycemia (HR 1.28, 95% CI 1.09 to 1.5, p=0.003). Hyperglycemia during chemotherapy increased the risk of all-cause mortality for the combined (HR 1.18, 95% CI 1.09 to 1.27, p<0.0001) and NHL (HR 1.16, 95% CI 1.04 to 1.28, p=0.007) cohorts., Conclusions: Hyperglycemia is common during hematologic chemotherapy treatment and is associated with a modest increased risk of all-cause mortality. Routine screening, monitoring, and management of hyperglycemia should be an integral part of treatment plans for leukemia, NHL, or HL, with or without glucocorticoid administration., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Stress hyperglycemia and lactates have been used separately as markers of a severe clinical condition and poor outcomes in patients with myocardial infarction (MI). However, the interplay between glucose and lactate metabolism in patients with MI have not been sufficiently studied. The aim in the present study was to examine the relationship of glycemia on admission (AG) and lactate levels and their impact on the outcome in non-diabetic MI patients treated with percutaneous coronary intervention (PCI)., Methods: A total of 405 consecutive, non-diabetic, MI patients were enrolled in this retrospective, observational, single-center study. Clinical characteristic including glucose and lactate levels on admission and at 30-day mortality were assessed., Results: Patients with stress hyperglycemia (AG ≥ 7.8 mmol/L, n = 103) had higher GRACE score (median [interquartile range]: 143.4 (115.4-178.9) vs. 129.4 (105.7-154.5), p = 0.002) than normoglycemic patients (AG level < 7.8 mmol/L, n = 302). A positive correlation of AG with lactate level (R = 0.520, p < 0.001) was observed. The coexistence of both hyperglycemia and hyperlactatemia (lactate level ≥ 2.0 mmol/L) was associated with lower survival rate in the Kaplan-Meier estimates (p < 0.001). In multivariable analysis both hyperglycemia and hyperlactatemia were related to a higher risk of death at 30-day follow-up (hazard ratio [HR] 3.21, 95%, confidence interval [CI] 1.04-9.93; p = 0.043 and HR 7.08; 95% CI 1.44-34.93; p = 0.016, respectively) CONCLUSIONS: There is a relationship between hyperglycemia and hyperlactatemia in non-diabetic MI patients treated with PCI. The coexistence of both hyperglycemia and hyperlactatemia is associated with lower survival rate and are independent predictors of 30-day mortality in MI patients and these markers should be evaluated simultaneously.

Background: Stress hyperglycemia can persist during an intensive care unit (ICU) stay and result in prolonged requirement for insulin (PRI). The impact of PRI on ICU patient outcomes is not known. We evaluated the relationship between PRI and Day 90 mortality in ICU patients without previous diabetic treatments., Methods: This is a post hoc analysis of the CONTROLING trial, involving 12 French ICUs. Patients in the personalized glucose control arm with an ICU length of stay ≥ 5 days and who had never previously received diabetic treatments (oral drugs or insulin) were included. Personalized blood glucose targets were estimated on their preadmission usual glycemia as estimated by their glycated A1c hemoglobin (HbA1C). PRI was defined by insulin requirement. The relationship between PRI on Day 5 and 90-day mortality was assessed by Cox survival models with inverse probability of treatment weighting (IPTW). Glycemic control was defined as at least one blood glucose value below the blood glucose target value on Day 5., Results: A total of 476 patients were included, of whom 62.4% were male, with a median age of 66 (54-76) years. Median values for SAPS II and HbA1C were 50 (37.5-64) and 5.7 (5.4-6.1)%, respectively. PRI was observed in 364/476 (72.5%) patients on Day 5. 90-day mortality was 23.1% in the whole cohort, 25.3% in the PRI group and 16.1% in the non-PRI group (p < 0.01). IPTW analysis showed that PRI on Day 5 was not associated with Day 90 mortality ( IPTW HR = 1.22; CI 95% 0.84-1.75; p = 0.29), whereas PRI without glycemic control was associated with an increased risk of death at Day 90 ( IPTW HR = 3.34; CI 95% 1.26-8.83; p < 0.01)., Conclusion: In ICU patients without previous diabetic treatments, only PRI without glycemic control on Day 5 was associated with an increased risk of death. Additional studies are required to determine the factors contributing to these results., (© 2022. The Author(s).)

Background: Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19., Methods: This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140-180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality., Results: Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140-180 mg) and 41.1% (>180 mg/dL), p <.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p <.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality., Conclusions: Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.

Background and Aims: Hyperglycemia is a condition often found in hospitalized patients due to stress injury, parenteral nutrition or medications administered during hospitalization. According to previous studies, hyperglycemia could be an independent predictor of mortality. The objective of the study is to assess the risk of mortality in non-diabetic patients with hyperglycemia during hospitalization., Methods: In this systematic review, we conducted literature reviews on several databases. Twelve studies were retrieved and critically reviewed using NOS., Results: A majority of the studies reported that hospital related hyperglycemia increased the mortality rate., Conclusions: Hospital related hyperglycemia is an independent predictor factor for both in-hospital and long-term mortality., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Aim: Diabetes has been identified as a risk factor for poor outcomes in patients with COVID-19. We examined the association of hyperglycaemia, both in the presence and absence of pre-existing diabetes, with severity and outcomes in COVID-19 patients., Methods: Data from 74,148 COVID-19-positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre-existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl)., Results: Among patients with and without a pre-existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70-180 mg/dl) in both groups (non-diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre-existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52-2.07); among patients without a pre-existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79-3.37)., Conclusion: This retrospective analysis identified hyperglycaemia in COVID-19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID-19 morality in the inpatient environment., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: The prognostic role of hyperglycemia in patients with myocardial infarction and obstructive coronary arteries (MIOCA) is acknowledged, while data on non-obstructive coronary arteries (MINOCA) are still lacking. Recently, we demonstrated that admission stress-hyperglycemia (aHGL) was associated with a larger infarct size and inflammatory response in MIOCA, while no differences were observed in MINOCA. We aim to investigate the impact of aHGL on short and long-term outcomes in MIOCA and MINOCA patients., Methods: Multicenter, population-based, cohort study of the prospective registry, designed to evaluate the prognostic information of patients admitted with acute myocardial infarction to S. Orsola-Malpighi and Maggiore Hospitals of Bologna metropolitan area. Among 2704 patients enrolled from 2016 to 2020, 2431 patients were classified according to the presence of aHGL (defined as admission glucose level ≥ 140 mg/dL) and AMI phenotype (MIOCA/MINOCA): no-aHGL (n = 1321), aHGL (n = 877) in MIOCA and no-aHGL (n = 195), aHGL (n = 38) in MINOCA. Short-term outcomes included in-hospital death and arrhythmias. Long-term outcomes were all-cause and cardiovascular mortality., Results: aHGL was associated with a higher in-hospital arrhythmic burden in MINOCA and MIOCA, with increased in-hospital mortality only in MIOCA. After adjusting for age, gender, hypertension, Killip class and AMI phenotypes, aHGL predicted higher in-hospital mortality in non-diabetic (HR = 4.2; 95% CI 1.9-9.5, p = 0.001) and diabetic patients (HR = 3.5, 95% CI 1.5-8.2, p = 0.003). During long-term follow-up, aHGL was associated with 2-fold increased mortality in MIOCA and a 4-fold increase in MINOCA (p = 0.032 and p = 0.016). Kaplan Meier 3-year survival of non-hyperglycemic patients was greater than in aHGL patients for both groups. No differences in survival were found between hyperglycemic MIOCA and MINOCA patients. After adjusting for age, gender, hypertension, smoking, LVEF, STEMI/NSTEMI and AMI phenotypes (MIOCA/MINOCA), aHGL predicted higher long-term mortality., Conclusions: aHGL was identified as a strong predictor of adverse short- and long-term outcomes in both MIOCA and MINOCA, regardless of diabetes. aHGL should be considered a high-risk prognostic marker in all AMI patients, independently of the underlying coronary anatomy. Trial registration data were part of the ongoing observational study AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation. ClinicalTrials.gov Identifier: NCT03883711., (© 2021. The Author(s).)

We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer ( p = 0.004), and needed more frequently insulin infusion therapy ( p = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy ( p = 0.001) and glucose delivered through artificial nutrition ( p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, p = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU ( r = -0.476, p = 0.001) and at days 2 ( r = -0.409, p = 0.007) and 3 ( r = -0.351, p = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.

Introduction: hyperglycemic emergencies (diabetic ketoacidosis and hyperglycemic hyperosmolar state) are the most common serious acute metabolic complications of diabetes which result in significant morbidity and mortality. There is paucity of data on hyperglycemic emergencies in Cameroon. The objective of this study was to investigate the precipitants and outcomes of patients admitted for hyperglycemic emergencies in the Buea Regional Hospital in the South West Region of Cameroon., Methods: in this retrospective study the medical records of patients admitted for hyperglycemic emergencies between 2013 and 2016 in the medical unit of the Buea Regional Hospital were reviewed. We extracted data on demographic characteristics, admission clinical characteristics, precipitants, and treatment outcomes. Logistic regression was used to determine predictors of mortality., Results: data were available for 60 patients (51.7% females) admitted for hyperglycemic emergencies. The mean age was 55.2±16.3 (range 18-86). Overall there were 51 (85%) cases of hyperosmolar hyperglycemic state. Twenty six (43.3%) of the patients had hypertension. The most common precipitants of hyperglycemic emergencies were infections (41.7%), newly diagnosed diabetes (33.3%) and non-adherence to medications (33.3%). Mean admission blood glucose was 574mg/dl±70.0mg/dl. The median length of hospital stay was 6 days. Overall case fatality rate was 21.7%. Six (46.2%) deaths were related to infections. Predictors of mortality were a Glasgow coma score <13(p<0.001), a diastolic blood pressure <60 mmHg (p=0.034) and a heart rate >90(0.057) on admission., Conclusion: admission for hyperglycemic emergencies in this semi-urban hospital is associated with abnormally high case fatality. Infections, newly diagnosed diabetes and non-adherence to medications are the commonest precipitants of hyperglycemic emergencies. Public health measures to reduce morbidity and mortality from hyperglycemic crisis are urgently needed., Competing Interests: The authors declare no competing interests., (Copyright: Clovis Nkoke et al.)

Background: Hyperglycemia is associated with mortality after trauma; however, few studies have simultaneously investigated the association of depth of shock and acute hyperglycemia. We evaluated lactate, as a surrogate measure for depth of shock, and glucose levels on mortality following severe blunt trauma. We hypothesize that measurements of both lactate and glucose are associated with mortality when considered simultaneously., Methods: This is a retrospective cohort study at a single academic trauma center. Inclusion criteria are age 18-89 years, blunt trauma, injury severity score (ISS) ≥15, and transferred from the scene of injury. All serum blood glucose and lactate values were analyzed within the first 24 hours of admission. Multiple metrics of glucose and lactate were calculated: first glucose (Glucadm) and lactate (Lacadm) at hospital admission, mean 24-hour after hospital admission glucose (Gluc24-hMean) and lactate (Lac24-hMean), maximum 24-hour after hospital admission glucose (Gluc24-hMax) and lactate (Lac24-hMax), and time-weighted 24-hour after hospital admission glucose (Gluc24-hTW) and lactate (Lac24-hTW). Primary outcome was in-hospital mortality. Multivariable logistic regression modeling assessed the odds ratio (OR) of mortality, after adjusting for confounding variables., Results: A total of 1439 trauma patients were included. When metrics of both glucose and lactate were analyzed, after adjusting for age, ISS, and admission shock index, only lactate remained significantly associated with mortality: Lacadm (OR, 1.28; 95% confidence interval [CI], 1.13-1.44); Lac24-hMean (OR, 1.86; 95% CI, 1.52-2.28); Lac24-hMax (OR, 1.39; 95% CI, 1.23-1.56); and Lac24-hTW (OR, 1.86; 95% CI, 1.53-2.26)., Conclusions: Lactate is associated with mortality in severely injured blunt trauma patients, after adjusting for injury severity, age, and shock index. However, we did not find evidence for an association of glucose with mortality after adjusting for lactate., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Aims/introduction: The aim of the present study was to clarify the pathophysiologies of hyperglycemic crises in Japanese patients., Materials and Methods: This was a retrospective study of patients with hyperglycemic crises admitted to Kumamoto Medical Center, Kumamoto, Japan, between 2012 and 2019. Patients were classified as having diabetic ketoacidosis (DKA), hyperglycemic hyperosmotic syndrome (HHS) or a mixed state of the two conditions (MIX), and laboratory data and levels of consciousness at hospital admission, as well as the rates of mortality and coagulation disorders, were compared., Results: The diagnostic criteria for hyperglycemic crisis were met in 144 cases, comprising 87 (60.4%), 38 (26.4%) and 19 (13.2%) cases of DKA, HHS and MIX, respectively. Type 1 diabetes was noted in 46.0 and 26.3% of patients in the DKA and MIX groups, respectively. Fibrin degradation product and D-dimer levels were significantly higher in the HHS group than in the DKA group (DKA and HHS groups: fibrin degradation product 7.94 ± 8.43 and 35.54 ± 51.80 μg/mL, respectively, P < 0.01; D-dimer 2.830 ± 2.745 and 14.846 ± 21.430 μg/mL, respectively, P < 0.01). Mortality rates were 5.7, 13.2 and 5.3% in the DKA, HHS and MIX groups, respectively. Seven patients (4.9%), four of whom were in the MIX group, had acute arterial occlusive diseases., Conclusions: The low frequency of type 1 diabetes in DKA and MIX might be responsible for reduced insulin secretion in Japanese populations. Patients with hyperglycemic crises have increased coagulability, and acute arterial occlusion needs to be considered, particularly in MIX., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aims/introduction: The predictive value of admission hyperglycemia in the long-term prognosis of acute myocardial infarction patients is still controversial. We aimed to investigate this value based on the diabetes status., Materials and Methods: We carried out a multicenter, retrospective study of 1,288 acute myocardial infarction patients enrolled in 11 hospitals between March 2014 and June 2019 in Chengdu, China. The patients were classified into those with diabetes and those without diabetes, each was further divided into: hyperglycemia and non-hyperglycemia subgroups, according to the optimal cut-off value of the blood glucose to predict all-cause mortality during follow up. The end-points were all-cause death and major adverse cardiovascular and cerebrovascular events, including all-cause death, non-fatal myocardial infarction, vessel revascularization and non-fatal stroke., Results: In the follow-up period of 15 months, we observed 210 (16.3%), 6 (0.5%), 57 (4.4%) and 34 (2.6%) cases of death, non-fatal myocardial infarction, revascularization and non-fatal stroke, respectively. The optimal cut-off values of admission blood glucose for patients with diabetes and patients without diabetes to predict all-cause mortality during follow up were 14.80 and 6.77 mmol/L, respectively. We divided patients with diabetes (n = 331) into hyperglycemia (n = 92) and non-hyperglycemia (n = 239), and patients without diabetes (n = 897) into hyperglycemia (n = 425) and non-hyperglycemia (n = 472). The cumulative rates of all-cause death and major adverse cardiovascular and cerebrovascular events among the patients in each hyperglycemia group was higher than that in the corresponding non-hyperglycemia group (P < 0.001). In patients without diabetes, admission hyperglycemia was an independent predictor of all-cause mortality and major adverse cardiovascular and cerebrovascular events., Conclusion: Admission hyperglycemia was an independent predictor for long-term prognosis in acute myocardial infarction patients without diabetes., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Whyte, Vas and Umpleby.)

Aims: To evaluate the frequency of diabetes and admission hyperglycaemia in Mexican COVID-19 patients, to describe the clinical and biochemical characteristics of patients with admission hyperglycaemia and to determinate the impact of diabetes and admission hyperglycaemia on COVID-19 severity and mortality., Methods: A multicentric study was performed in 480 hospitalized patients with COVID-19. Clinical and biochemical characteristics were evaluated in patients with admission hyperglycaemia and compared with non-hyperglycaemic patients. The effect of diabetes and admission hyperglycaemia on severity and risk of death were evaluated., Results: Age was 50.7 ± 13.6 years; 68.3% were male. Some 48.5% ( n  = 233) had admission hyperglycaemia; 29% ( n  = 139) of these patients had pre-existing diabetes. Patients with admission hyperglycaemia had more requirement of invasive mechanical ventilation (IMV), higher levels of urea, D-dimer and neutrophil-lymphocyte ratio (NLR), as well as lower lymphocyte count. An association between admission hyperglycaemia with IMV and D-dimer with glucose was found. Age ≥50 years (OR 2.09; 95%CI 1.37-3.17), pre-existing diabetes (OR 2.38; 95%CI 1.59-5.04) and admission hyperglycaemia (OR 8.24; 95%CI 4.74-14.32) were risk factors for mortality., Conclusions: Admission hyperglycaemia is presented in 48.5% of COVID-19 patients. Diabetes and admission hyperglycaemia are associated with the severity of disease and mortality. This study shows the devastating conjunction of hyperglycaemia and COVID-19. Clinical trial registration: Clinical characteristics of patients with COVID-19, DI/20/204/04/41 (Hospital General de Mexico) and NR-13-2020 (Hospital Regional de Alta Especialidad Ixtapaluca)., Competing Interests: The authors declare no conflict of interest in this study., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000-1.630, p = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012-1.674, p = 0.040) in multi-variate regression tests. Kaplan-Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group (p < 0.001), and subsequent multivariate Cox proportional analyses revealed that high hemoglobin A1c is an independent predictor for shorter BCR-free survival (HR 1.135, 95% CI 1.016-1.267, p = 0.024). Moreover, the high hemoglobin A1c group showed a significantly longer incontinence-free survival than the low hemoglobin A1c group (p = 0.001), and high preoperative hemoglobin A1c was also an independent predictor for longer incontinence-free survival in multivariate Cox analyses (HR 0.929, 95% CI 0.879-0.981, p = 0.008). The high preoperative hemoglobin A1c level was independently associated with worse oncological outcomes and also with inferior recovery of urinary continence after radical prostatectomy.

(1) Background: Recent evidence reported a reduced tolerance of macronutrient parenteral intakes in subjects in critically ill conditions. We designed a prospective cohort study to evaluate the effects of hyperglycemia (HG) related to parenteral nutrition (PN) on neurodevelopment (NDV) in survived preterm newborns. (2) Methods: Enrolled newborns with gestational age < 32 weeks or birth weight < 1500 g, were divided in two cohorts: (A) exposed to moderate or severe HG (glucose blood level > 180 mg/dL) in the first week of life; (B) not exposed to HG. We considered as the primary outcome the rate of preterm newborns survived without NDV delay at 24 months of life, evaluated with Bayley Scales of Infants Development III edition. (3) Results: We analyzed 108 (A 32 vs. B 76) at 24 months of life. Newborns in cohort A showed a higher rate of cognitive and motor delay (A 44% vs. B 22 %, p = 0.024; A 38% vs. B 8%, p < 0.001). When adjusting for background characteristics, HG remained a risk factor for motor delay. (4) Conclusions: High nutritional intakes through PN soon after birth increase the risk of HG. The consequences of this severe metabolic complication affect long-term NDV and survival in preterm newborns.

Objective: Diabetes is a known risk factor for mortality in Coronavirus disease 2019 (COVID-19) patients. Our objective was to identify prevalence of hyperglycaemia in COVID-19 patients with and without prior diabetes and quantify its association with COVID-19 disease course., Research Design and Methods: This observational cohort study included all consecutive COVID-19 patients admitted to John H Stroger Jr. Hospital, Chicago, IL from March 15, 2020 to May 3, 2020 and followed till May 15, 2020. The primary outcome was hospital mortality, and the studied predictor was hyperglycaemia [any blood glucose ≥7.78 mmol/L (140 mg/dL) during hospitalization]., Results: Of the 403 COVID-19 patients studied, 51 (12.7%) died; 335 (83.1%) were discharged while 17 (4%) were still in hospital. Hyperglycaemia occurred in 228 (56.6%) patients; 83 of these hyperglycaemic patients (36.4%) had no prior history of diabetes. Compared to the reference group no-diabetes/no-hyperglycaemia patients the no-diabetes/hyperglycaemia patients showed higher mortality [1.8% versus 20.5%, adjusted odds ratio 21.94 (95% confidence interval 4.04-119.0), P < 0.001]; improved prediction of death (P = 0.01) and faster progression to death (P < 0.01). Hyperglycaemia within the first 24 and 48 h was also significantly associated with mortality (odds ratio 2.15 and 3.31, respectively)., Conclusions: Hyperglycaemia without prior diabetes was common (20.6% of hospitalized COVID-19 patients) and was associated with an increased risk of and faster progression to death. Development of hyperglycaemia in COVID-19 patients who do not have diabetes is an early indicator of progressive disease., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Aims/introduction: To identify thresholds for postprandial hyperglycemia and hypertriglyceridemia predictive of all-cause mortality in patients with type 2 diabetes., Materials and Methods: A total of 1,928 patients with type 2 diabetes visited our clinic for the first time from 1995 to 1999 and were followed up for ≥1 year. During the first year, 2-h post-breakfast blood glucose (2h-BG) levels were measured in 1,122 patients (BG cohort) and postprandial serum triglyceride (ppTG) levels were measured in 1,826 patients (TG cohort). Patients were retrospectively followed until 2017 and administered questionnaires. Associations between 2h-BG and ppTG levels and mortality risk were assessed by the multivariate Cox regression analysis., Results: Over of 17,429 person-years, 162 deaths occurred in the BG cohort, and over 28,026 person-years, 253 deaths occurred in the TG cohort. Hazard ratios (HRs) with 95% confidence intervals for all-cause mortality per 1-standard deviation increases in 2h-BG and ppTG were 1.34 (1.08-1.67) and 1.24 (1.06-1.45), respectively. HRs showed increasing trends across quintiles of 2h-BG (P = 0.034) and ppTG (P = 0.007). The HR was significantly elevated (2.37, 1.26-4.47) in the fifth quintile of 2h-BG (≥13.8 mmol/L) compared with the first quintile (<7.0 mmol/L; P = 0.008). The HR was also significantly elevated (1.63, 1.03-2.60) in the fifth quintile of ppTG (≥2.30 mmol/L) compared with the first quintile (<0.91 mmol/L; P = 0.038)., Conclusions: Postprandial hyperglycemia and hypertriglyceridemia were associated with all-cause mortality in patients with type 2 diabetes. We propose thresholds of 13.8 mmol/L 2h-BG and 2.30 mmol/L ppTG to identify patients at increased risk of mortality., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objectives: Copeptin, an equimolar indicator of serum antidiuretic hormone levels, has been associated with higher mortality in critically ill patients and with the development of diabetes in the general population. The aim of the present study was to investigate the association of copeptin levels with glycemic parameters in critically ill patients and to compare the time-course of copeptin in survivors and non-survivors., Design: Prospective cohort study., Patients: From June to October 2019, critically ill patients were prospectively enrolled and followed for 90 days., Measurements: Plasma copeptin levels were determined at intensive care unit (ICU) admission (copeptin T1), 24 h (copeptin T2), and 48 h (copeptin T3) after study entry. Blood glucose and glycated hemoglobin levels were measured. ICU, in-hospital, and 90-day mortality, and length of stay in the ICU and hospital were evaluated., Results: 104 patients were included. No significant correlation was detected between copeptin levels and blood glucose (r = -0.17, p = 0.09), HbA1c (r = 0.01, p = 0.9), glycemic gap (r = -0.16, p = 0.11), and stress hyperglycemia ratio (r = -0.14, p = 0.16). Copeptin T3 levels were significantly higher in survivors than in non-survivors at hospital discharge (561 [370-856] vs 300 [231-693] pg/mL, p = 0.015) and at 90 days (571 [380-884] vs 300 [232-698] pg/mL, p = 0.03)., Conclusions: No significant correlations were found between copeptin levels and glycemic parameters, suggesting that copeptin is not a relevant factor in the induction of hyperglycemia during critical illness. Copeptin levels at ICU day 3 were higher in survivors than in non-survivors., Competing Interests: The authors have declared that no competing interests exist.

The independent association of diabetes and hyperglycemia on the outcomes of sepsis remains unclear. We conducted retrospective cohort analyses of outcomes among patients with community-onset sepsis admitted to Shamir Medical Center, Israel (08-12/2016). Statistical associations were queried by Cox and logistic regressions, controlled for by matched propensity score analyses. Among 1527 patients with community-onset sepsis, 469 (30.7%) were diabetic. Diabetic patients were significantly older, with advanced complexity of comorbidities, and were more often exposed to healthcare environments. Despite statistically significant univariable associations with in-hospital and 90-day mortality, the adjusted Hazard Ratios (aHR) were 1.21 95% CI 0.8-1.71, p = 0.29 and 1.13 95% CI 0.86-1.49, p = 0.37, respectively. However, hyperglycemia at admission (i.e., above 200 mg/dl (was independently associated with: increased in-hospital mortality, aHR 1.48 95% CI 1.02-2.16, p = 0.037, 30-day mortality, aHR 1.8 95% CI 1.12-2.58, p = 0.001), and 90-day mortality, aHR 1.68 95% CI 1.24-2.27, p = 0.001. This association was more robust among diabetic patients than those without diabetes. In this study, diabetes was not associated with worse clinical outcomes in community-onset sepsis. However, high glucose levels at sepsis onset are independently associated with a worse prognosis, particularly among diabetic patients. Future trials should explore whether glycemic control could impact the outcomes and should be part of the management of sepsis, among the general adult septic population.

While most people with diabetes have type 2 disease, a non-negligible minority develops a secondary diabetes. Post-pancreatitis diabetes mellitus (PPDM) is an exemplar secondary diabetes that represents a sequela of pancreatitis - the most common disease of the exocrine pancreas. Although this type of diabetes has been known as a clinical entity since the late 19th century, early 21st century high-quality epidemiological, clinical, and translational studies from around the world have amassed a sizeable body of knowledge that have led to a renewed understanding of PPDM. People have at least two-fold higher lifetime risk of developing diabetes after an attack of pancreatitis than those in the general population without a history of diseases of the exocrine pancreas. PPDM is caused by acute pancreatitis (including non-necrotising pancreatitis, which constitutes the majority of acute pancreatitis) in four-fifth of cases and chronic pancreatitis in one-fifth of cases. Moreover, the frequency of incident diabetes is not considerably lower after acute pancreatitis than after chronic pancreatitis. Recurrent attacks of pancreatitis and exocrine pancreatic dysfunction portend high risk for PPDM, but are not mandatory for its development. Further, young- or middle-aged non-obese men have an increased risk of developing PPDM. In comparison with type 2 diabetes, PPDM is characterised by poorer glycaemic control, higher risk of developing cancer (in particular, pancreatic cancer), younger age at death, and a higher risk of mortality. Metformin monotherapy is recommended as the first-line therapy for PPDM. Appropriate screening of individuals after an attack of pancreatitis, correct identification of PPDM, and apposite management is crucial with a view to improving the outcomes of this secondary but not inappreciable disease.

This retrospective study examined changes in fasting blood glucose (FBG) levels during hospitalization and their effect on risk of death for Coronavirus disease 2019 (COVID-19) patients without previously diagnosed diabetes. A model with low- and high-stable pattern trajectories was established based on a longitudinal change in FBG levels. We analyzed FBG trajectory-associated clinical features and risk factors for death due to COVID-19. Of the 230 enrolled patients, 44 died and 87.83% had a low-stable pattern (average FBG range: 6.63-7.54 mmol/L), and 12.17% had a high-stable pattern (average FBG range: 12.59-14.02 mmol/L). There were statistical differences in laboratory findings and case fatality between the two FBG patterns. Multivariable logistic regression analysis showed that increased neutrophil count (odds ratio [OR], 25.43; 95% confidence interval [CI]: 2.07, 313.03), elevated direct bilirubin (OR, 5.80; 95%CI: 1.72, 19.58), elevated creatinine (OR, 26.69; 95% CI: 5.82, 122.29), lymphopenia (OR, 8.07; 95% CI: 2.70, 24.14), and high-stable FBG pattern (OR, 8.79; 95% CI: 2.39, 32.29) were independent risk factors for higher case fatality in patients with COVID-19 and hyperglycemia but no history of diabetes. FBG trajectories were significantly associated with death risk in patients with COVID-19 and no diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Song, Zhang, Wang, Wang, Ma, Ma, Luo, Wang and Jin.)

Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04365634., Context: Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear., Objective: We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients., Design and Methods: In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups., Results: Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4 + T cells, CD8 + T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8 + T cells and NK cells than survivors., Conclusion: The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8 + T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Han, Ma, Wang, Yan, Wang, You, Wang, Chen, Guo, Chen, Ning and Luo.)

Background and Aims: Efficient analysis strategies for complex network with cardiovascular disease (CVD) risk stratification remain lacking. We sought to identify an optimized model to study CVD prognosis using survival conditional inference tree (SCTREE), a machine-learning method., Methods and Results: We identified 5379 new onset CVD from 2006 (baseline) to May, 2017 in the Kailuan I study including 101,510 participants (the training dataset). The second cohort composing 1,287 CVD survivors was used to validate the algorithm (the Kailuan II study, n = 57,511). All variables (e.g., age, sex, family history of CVD, metabolic risk factors, renal function indexes, heart rate, atrial fibrillation, and high sensitivity C-reactive protein) were measured at baseline and biennially during the follow-up period. Up to December 2017, we documented 1,104 deaths after CVD in the Kailuan I study and 170 deaths in the Kailuan II study. Older age, hyperglycemia and proteinuria were identified by the SCTREE as main predictors of post-CVD mortality. CVD survivors in the high risk group (presence of 2-3 of these top risk factors), had higher mortality risk in the training dataset (hazard ratio (HR): 5.41; 95% confidence Interval (CI): 4.49-6.52) and in the validation dataset (HR: 6.04; 95%CI: 3.59-10.2), than those in the lowest risk group (presence of 0-1 of these factors)., Conclusion: Older age, hyperglycemia and proteinuria were the main predictors of post-CVD mortality., Trial Registration: ChiCTR-TNRC-11001489., Competing Interests: Declaration of competing interest Authors have nothing to disclose., (Copyright © 2020. Published by Elsevier B.V.)

Background and Aims: Hyperglycemia at hospital admission is a common finding in patients with STEMI. However, whether elevated acute glycemia in these patients may have a direct impact on worsening prognosis or is just a marker of a greater neurohormonal activation in response to the infarction is still unsettled. We sought to investigate the prognostic impact of hyperglycemia at hospital admission in patients undergoing primary PCI (pPCI) for STEMI, and the influence of the presence of diabetes mellitus (DM) on its prognostic impact., Methods: and Results, We enrolled 2958 consecutive STEMI patients treated by pPCI. Hyperglycemia was defined as plasma glucose >198 mg/dL (or >11 mmol/L). Patients with hyperglycemia showed a greater risk-profile; they also experienced a higher mortality both at univariable (17.6% vs 5.2%, p < 0.001) and multivariable (HR 1.9, 95%IC 1.5-2.9, p = 0.001) analysis. However, after stratification for DM presence, hyperglycemia resulted as an independent predictor of mortality only in patients without DM (HR 2, 95%IC 1.2-3.4, p = 0.01)., Conclusion: Hyperglycemia in the setting of myocardial infarction treated with primary PCI in an independent predictor of all-cause mortality in patients without diabetes; in patients with diabetes, its prognostic impact seems attenuated., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) has been declared a global pandemic. COVID-19 is more severe in people with diabetes. The identification of risk factors for predicting disease severity in COVID-19 patients with type 2 diabetes mellitus (T2DM) is urgently needed., Methods: Two hundred and thirty-six patients with COVID-19 were enrolled in our study. The patients were divided into 2 groups: COVID-19 patients with or without T2DM. The patients were further divided into four subgroups according to the severity of COVID-19 as follows: Subgroup A included moderate COVID-19 patients without diabetes, subgroup B included severe COVID-19 patients without diabetes, subgroup C included moderate COVID-19 patients with diabetes, and subgroup D included severe COVID-19 patients with diabetes. The clinical features and radiological assessments were collected and analyzed. We tracked the dynamic changes in laboratory parameters and clinical outcomes during the hospitalization period. Multivariate analysis was performed using logistic regression to analyze the risk factors that predict the severity of COVID-19 with T2DM., Results: Firstly, compared with the nondiabetic group, the COVID-19 with T2DM group had a higher erythrocyte sedimentation rate (ESR) and levels of C-reactive protein (CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and procalcitonin (PCT) but lower lymphocyte counts and T lymphocyte subsets, including CD3+ T cells, CD8+ T cells, CD4+ T cells, CD16 + CD56 cells, and CD19+ cells. Secondly, compared with group A, group C had higher levels of Fasting blood glucose (FBG), IL-6, TNF-α, and neutrophils but lower lymphocyte, CD3+ T cell, CD8+ T cell, and CD4+ T cell counts. Similarly, group D had higher FBG, IL-6 and TNF-α levels and lower lymphocyte, CD3+ T cell, CD8+ T cell, and CD4+ T cell counts than group B. Thirdly, binary logistic regression analysis showed that HbA1c, IL-6, and lymphocyte count were risk factors for the severity of COVID-19 with T2DM. Importantly, COVID-19 patients with T2DM were more likely to worsen from moderate to severe COVID-19 than nondiabetic patients. Of note, lymphopenia and inflammatory responses remained more severe throughout hospitalization for COVID-19 patients with T2DM., Conclusion: Our data suggested that COVID-19 patients with T2DM are more likely to develop severe COVID-19 than those without T2DM and that hyperglycemia associated with the lymphopenia and inflammatory responses in COVID-19 patients with T2DM., (Copyright © 2020 Elsevier Inc. All rights reserved.)