The Potential Diagnostic and Predictive Role of HbA1c in Diabetic, Septic Patients - a Retrospective Single Center Study

The Potential Diagnostic and Predictive Role of HbA1c in Diabetic, Septic Patients - a Retrospective Single Center Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Original Research The Potential Diagnostic and Predictive Role of HbA1c in Diabetic, Septic Patients - a Retrospective Single Center Study Imre Juhász, Janka Juhász, Hajnalka Lőrincz, Ildikó Seres, Lilla Végh, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-127448/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 18 Mar, 2022 Read the published version in Emergency Medicine International → Version 1 posted You are reading this latest preprint version Abstract Background: Diabetes mellitus is a major risk factor of sepsis. The potential role of hemoglobin A1c (HbA1c) in diabetic, septic patients has not yet been studied. Results: In our retrospective study we included diabetic, septic patients - in whom the diagnosis of sepsis was based on the Systemic Inflammatory Response Syndrome (SIRS) criteria (112 patients, SIRS group) - who had HbA1c levels measured either in the previous 30 days (SIRS 30d subgroup – 39 patients) or within 24 hours after their Emergency Department admission (SIRS 24h subgroup – 73 patients). We later selected those patients from the SIRS group, whose Sequential Organ Failure Assessment (SOFA) score was ≥ 2 (55 patients, SOFA group) and these patients were also divided based on the time of HbA1c measurement (SOFA 30d subgroup – 21 patients and SOFA 24h subgroup – 34 patients). We analyzed the relationship between laboratory parameters, length of hospital stay and HbA1c. We found a significant positive correlation between glucose and HbA1c, significant negative correlations between white blood cell count (WBC) and glucose, WBC and HbA1c levels in the SIRS 24h and SOFA 24h subgroups. Furthermore there was a significant positive correlation between length of hospital stay and HbA1c in the SOFA 24h subgroup. No significant correlations were found in the SIRS 30d and SOFA 30d subgroups. Conclusions: Based on our results normal WBC with elevated HbA1c might be considered a positive SIRS criterium in diabetic, SIRS 24h patients. Besides this potential diagnostic role, HbA1c might also be an additional prognostic biomarker in diabetic, SOFA 24h patients. Critical Care & Emergency Medicine sepsis diabetes HbA1c white blood cell risk prediction Figures Figure 1 Figure 2 Figure 3 Background Sepsis is a potentially life-threatening condition. Its definition keeps on changing as we learn more and more about the underlying pathomechanism of the disease. Before 2016 the Systemic Inflammatory Response Syndrome (SIRS) criteria was used for the diagnosis of sepsis: if at least 2 out of 4 clinical findings were present in a patient with a likely infection the diagnsosis of sepsis was confirmed. The SIRS criteria are the following: tachycardia (heart rate > 90), hypothermia/fever (temperature 38 °C), hyperventilation/hypocapnia (respiratory rate > 20 or PaCO₂ < 32 mmHg), leukopenia/leukocytosis (white blood cell count 12,000/mm³ or > 10% bands). The definition distinguished sepsis, severe sepsis and septic shock ( 1 – 4 ). In 2016 the definition of sepsis changed once again: the SIRS criteria as well as the definition of severe sepsis were no longer recommended. According to the new definition sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) scores have been introduced ( 4 ). The diagnostic algorithm of sepsis has changed: in a patient with a likely infection the use of the quick SOFA score is recommended (it consists of 3 components: systolic blood pressure ≤ 100 mmHg, altered mental status, respiratory rate ≥ 22). According to the new recommendations a positive qSOFA Score (≥ 2 points) should prompt the calculation of the SOFA score to confirm the diagnosis of sepsis. If the qSOFA score is negative (< 2 points) but sepsis is still likely, we should also calculate the SOFA score. In a patient with a negative qSOFA score (< 2 points) and an unlikely infection, sepsis can be excluded. If a patient’s SOFA score is ≥ 2 the diagnosis of sepsis is confirmed. The SOFA score consists of the following: platelet count, bilirubin and creatinine levels, mean arterial pressure (MAP) or administration of vasoactive agents, altered mental status (based on the Glasgow Coma Scale) and PaO2/FiO2. Septic shock is a form of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by vasopressor requirement to maintain a MAP of 65 mmHg or greater and serum lactate levels greater than 2 mmol/L in the absence of hypovolemia ( 4 ). Lots of studies have been published since 2016 in which the SIRS, qSOFA and SOFA criteria have been compared and data are controversial ( 5 ). Some results have shown inferior sensitivity of the qSOFA score compared to the previously favored SIRS criteria in the diagnosis of sepsis ( 6 – 9 ). Partly due to this, the 2016 recommendations are not universally accepted, and many countries still favor the previous diagnostic criteria and therefore the SIRS criteria. Sepsis is usually bacterial in origin (caused mainly by Gram positive bacteria), however viral and fungal causes could also be in the background ( 10 ). Its global incidence is increasing, and it can be as high as 437/100000/year ( 11 ). Major risk factors of sepsis include: advanced age (≥ 65 years), previous hospitalization (especially in the previous 90 days, intensive care unit admission, nosocomial infections, community-acquired pneumonia), immunosuppression (e.g. neoplasms, renal failure, liver failure, AIDS, splenectomy) and genetic factors ( 10 , 12 – 23 ). Diabetes mellitus, a metabolic disorder which has become a global health burden partly due to its rising incidence, is another major risk factor for sepsis ( 24 ). Immune response is severely altered in diabetics: neutrophil chemotaxis, phagocytosis, intracellular bactericide activity, opsonization as well as cell-mediated immunity are all affected ( 25 – 29 ). Therefore, infections are more common in diabetics compared to non-diabetic individuals. Poor glycemic control and hyperglycemia further increases the chance of infections in diabetics ( 25 – 29 ). Hemoglobin in newly formed red blood cells is minimally glycated. The membrane of circulating red blood cells is permeable to glucose therefore it could be irreversibly attached to hemoglobin in a non-enzymatic way. HbA1c gives us information regarding mean blood glucose concentration over the lifespan of red blood cells (120 days) and its value correlates best with mean blood sugar levels over the previous 8–12 weeks. HbA1c is widely used nowadays to diagnose diabetes and monitor carbohydrate metabolism in diabetics ( 30 – 37 ), however its potential role in diabetic, septic patients has not yet been studied. Results Diabetic, septic patients with HbA1c levels measured within 24 hours after emergency department admission SIRS 24 h patients SIRS 24 h patients were 72.8 ± 12.7 years old (73 patients, 47 females, 26 males). All our patients were type II diabetics. Anthropometric data, past medical history, anti-diabetic therapy, laboratory parameters of patients as well as length of hospital stay in survivors were summarized in a table (Table 1 ). We analyzed the relationship between laboratory parameters and HbA1c as well as the correlation between length of hospital stay and HbA1c. Additionally we examined the relationship between leukocyte count and glucose, platelet count and glucose, and length of hospital stay and glucose levels. (Fig. 1 .). In these patients there was a significant positive correlation between glucose and HbA1c levels (p < 0.001) (Fig. 2 /a). We found significant negative correlations between white blood cell count and glucose (p = 0.01) (Fig. 2 /b), white blood cell count and HbA1c levels (p = 0.001) (Fig. 2 /c). The same correlations were observed in most cases even if patients were divided based on gender, anti-diabetic therapy (oral anti-diabetic agents vs. insulin therapy), age (< 65 yrs vs.≥65 yrs) and hospitalization in the previous 90 days (Table 2 ). Table 1 Anthropometric data, anti-diabetic therapy and laboratory parameters of diabetic, SIRS 24 h and SOFA 24 h septic patients. Data are presented as mean ± standard deviation or median (lower-upper quartile). Diabetic, septic patients Criteria SIRS 24 h group SOFA 24 h group Number of patients (n) 73 (47f/26 m) 34 (21f/13 m) Age (years) 72.8 ± 12.7 73.9 ± 12.3 Type 2 diabetes (n) 73 34 Comorbidities Hypertension (n; %) 67 (91.8) 31 (91.2) Dyslipidemia (n; %) 31 (42.5) 12 (35.3) IHD/AMI/PCI/CABG (n; %) 32 (43.8) 18 (52.9) TIA/stroke (n; %) 15 (20.6) 6 (17.7) Peripheral arterial disease (n; %) 42 (57.5) 18 (52.9) Chronic kidney disease (n; %) 27 (37.0) 13 (38.2) Anti-diabetic medications Metformin (n; %) 30 (41.1) 11 (32.4) Sulphonyl urea (n; %) 24 (32.9) 10 (29.4) DPP4 (n; %) 4 (5.5) 0 Insulin (n; %) 18 (24.7) 11 (32.4) Laboratory parameters Glucose (mmol/l) 11.5 (7.7–16.3) 12.05 (8.5–19.2) HbA1C (%) 7.47 ± 1.8 7.26 ± 1.9 Urea (mmol/l) 8.4 (6-12.3) 9.85 (6.2–19.4) Creatinine (µmol/l) 99 (77–137) 118 (95–172) Glomerular filtration rate (ml/min*1.73 m2) 52 (38–75) 42 (27–61) C-reactive protein (mg/l) 77 (21-151.5) 108 (21.3-246.3) AST (U/L) 21 (17-33.5) 25 (16–42) GGT (U/L) 35 (21–69) 40 (16–124) ALT (U/L) 21 (14–32) 21 (14–37) Total bilirubin (µmol/l) 10 (6.5–17.4) 11.2 (6.3–33.6) White blood cell count (G/L) 15.8 ± 6.1 17.3 ± 7.3 Red blood cell count (T/L) 4.3 ± 0.7 4.3 ± 0.7 Hemoglobin concentration (g/l) 129.8 ± 22.3 133.8 ± 19.4 Thrombocyte (G/L) 252.6 ± 76.9 251.0 ± 92.8 Length of hospital stay (day) 8 (6-11.5) 8 (7-11.5) Table 2 Correlations between various laboratory parameters in subgroups of diabetic, SIRS 24 h septic patients. Abbreviations: CRP, C-reactive protein; HbA1c, hemoglobin A1c; LOS, length of stay in survivors; RBC, red blood cell; THR, thrombocyte; WBC, white blood cell. n glucose vs. HbA1c urea vs. HbA1c creatinine vs. HbA1c CRP vs. HbA1c bilirubin vs. HbA1c WBC vs. glucose WBC vs. HbA1c RBC vs. glucose RBC vs. HbA1c THR vs. HbA1c LOS vs. HbA1c LOS vs. glucose LOS vs. WBC All 73 r = 0.74 p < 0.001 ns ns ns ns r=-0.29 p = 0.01 r=-0.37 p = 0.001 ns ns ns ns ns ns males 26 r = 0.84 p < 0.001 ns ns ns r=-0.43 p = 0.05 ns r=-0.48 p = 0.01 ns ns r=-0.46 p = 0.02 ns ns ns females 47 r = 0.70 p < 0.001 ns ns ns ns r=-0.28 p = 0.05 r=-0.32 p = 0.02 ns ns ns ns ns ns non-insulin 53 r = 0.76 p < 0.001 ns ns ns ns r=-0.28 p = 0.04 r=-0.35 p = 0.01 ns ns ns ns ns ns insulin 18 r = 0.69 p = 0.001 ns ns ns ns ns r=-0.52 p = 0.03 ns ns ns ns r = 0.57 p = 0.02 ns under 65 yrs 17 r = 0.87 p < 0.001 ns ns ns ns ns r=-0.53 p = 0.03 ns ns ns ns ns ns over 65 yrs 56 r = 0.70 p < 0.001 ns ns ns ns r=-0.28 p = 0.04 r=-0.33 p = 0.01 ns ns ns ns ns ns Not stay within 90 days 66 r = 0.77 p < 0.001 ns ns ns ns r=-0.32 p = 0.01 r=-0.38 p = 0.001 ns ns ns ns ns ns Stay within 90 days 7 ns ns ns ns ns ns ns ns ns ns ns ns ns SOFA 24 h patients 34 type II diabetic, septic patients were in the SOFA 24 h group (21 females, 13 males, age: 74 ± 12.3 years). Anthropometric data, past medical history, anti-diabetic therapy, laboratory parameters of patients as well as length of hospital stay in survivors were summarized in a table (Table 1 ). We also analyzed the relationship between laboratory parameters and HbA1c as well as the correlation between length of hospital stay and HbA1c. Additionally we examined the relationship between leukocyte count and glucose, platelet count and glucose, and length of hospital stay and glucose levels. There was a significant positive correlation between glucose and HbA1c levels in the SOFA 24 h group, similarly to the one we found in SIRS 24 h patients (p < 0.001) (Fig. 3 /a). We also found significant negative correlations between white blood cell count and glucose (p = 0.02) (Fig. 3 /b) and white blood cell count and HbA1c levels in SOFA 24 h patients (p = 0.02) (Fig. 3 /c). Additionally, there was a significant positive correlation between HbA1c levels and length of hospital stay in survivors (p = 0.01) (data not shown). The previous correlations in the SOFA 24 h group were observed in most cases even if patients were divided based on gender, anti-diabetic therapy (oral anti-diabetic agents vs. insulin therapy), age (< 65 yrs vs.≥65 yrs) and hospitalization in the previous 90 days (Table 3 ). Table 3 Correlations between various laboratory parameters in subgroups of diabetic, SOFA 24 h septic patients. Abbreviations: CRP, C-reactive protein; HbA1c, hemoglobin A1c; LOS, length of stay in survivors; RBC, red blood cell; THR, thrombocyte; WBC, white blood cell. n glucose vs. HbA1c urea vs. HbA1c creatinine vs. HbA1c CRP vs. HbA1c bilirubin vs. HbA1c WBC vs. glucose WBC vs. HbA1c RBC vs. glucose RBC vs. HbA1c THR vs. HbA1c LOS vs. HbA1c LOS vs. glucose LOS vs. WBC All 34 r = 0.80 p = 0.001 ns ns ns ns r=-0.39 p = 0.02 r=-0.41 p = 0.02 ns ns ns r = 0.45 p = 0.01 r = 0.57 p = 0.001 ns males 13 r = 0.95 p = 0.001 ns ns ns r=-0.59 p = 0.05 ns ns ns ns r=-0.62 p = 0.02 ns ns ns females 21 r = 0.73 p = 0.001 ns ns ns ns ns ns ns ns ns r = 0.58 p = 0.01 r = 0.72 p = 0.001 ns non-insulin 22 r = 0.82 p = 0.001 ns ns ns ns r=-0.42 p = 0.05 r=-0.44 p = 0.03 ns ns ns r = 0.56 p = 0.05 r = 0.43 p = 0.01 ns insulin 11 r = 0.79 p = 0.005 ns ns ns ns ns ns ns ns ns r = 0.67 p = 0.04 r = 0.65 p = 0.05 ns under 65 yrs 7 r = 0.84 p = 0.02 ns ns ns ns ns r=-0.80 p = 0.03 ns ns ns r = 0.82 p = 0.02 r = 0.91 p = 0.004 ns over 65 yrs 27 r = 0.80 p = 0.001 ns ns ns ns ns ns ns ns ns r = 0.45 p = 0.02 r = 0.55 p = 0.004 ns Not stay within 90 days 29 r = 0.80 p = 0.001 ns ns ns ns r=-0.43 p = 0.02 r=-0.41 p = 0.03 ns ns ns r = 0.62 p = 0.001 r = 0.73 p = 0.001 ns Stay within 90 days 5 r = 0.96 p = 0.01 ns ns ns ns ns ns ns ns ns ns ns ns Diabetic, septic patients with HbA1c levels measured in the previous 30 days before their emergency department admission SIRS 30d and SOFA 30d patients There were 39 diabetic, septic patients in the SIRS 30d group. We studied the same correlations that were previously examined in the SIRS 24 h group. We did not find any significant correlation in this population even if we later selected and examined patients whose SOFA score was positive (≥ 2) (SOFA 30d group, 21 patients) (data not shown). Discussion This is the first study to evaluate the potential role of HbA1c in diabetic, septic patients. In SIRS 24 h patients we found a significant positive correlation between glucose and HbA1c levels, while significant negative correlations were observed between white blood cell count and glucose, white blood cell count and HbA1c. Correlations were observed even if patients were divided based on gender, anti-diabetic therapy (oral anti-diabetic agents vs. insulin therapy), age (< 65 yrs vs.≥65 yrs) and hospitalization in the previous 90 days. One possible explanation behind the observed negative correlations between white blood cell count and glucose, white blood cell count and HbA1c is glucose toxicity, a phenomenon previously described in pancreatic beta cells ( 38 – 40 ). According to previous studies, hyperglycemia in diabetic patients increases oxidative stress and induces glucose-induced apoptosis mainly in metabolically active cells (e.g. white blood cells in sepsis), resulting in cell death. There are some diabetic, septic patients - in whom sepsis is diagnosed based on the SIRS criteria - whose white blood cell count is normal, despite being septic. These diabetic, septic patients with normal white blood cell counts (WBC count between 4–12 × 10 9 /l) have higher HbA1c levels. This observation is crucial as white blood cell count is an important part of the SIRS criteria (positive criterium: white blood cell count 12,000/mm³ or > 10% bands). It may occur in diabetic, septic patients - in whom diagnosis is based on the SIRS criteria - that white blood cell count is normal (between 4–12 × 10 9 /l) and there is only one other positive SIRS criterium (heart rate > 90, temperature 38 °C, respiratory rate > 20 or PaCO₂ < 32 mmHg). According to the definition of sepsis - based on the SIRS criteria - these patients are not septic however the potential life-threatening immune processes might have already started. HbA1c - based on the negative correlation found between white blood cell count and HbA1c levels - can be a useful tool in finding these patients: in diabetic patients, normal white blood cell count (4–12 × 10 9 /l) with elevated HbA1c levels should be considered a positive SIRS criterium. Therefore HbA1c – measured within 24 hours after admission (preferably upon arrival) - could turn out to be an efficient way to identify these diabetic, septic patients early and initiate sepsis treatment accordingly. Further, large, multi-centric studies are needed to confirm our hypothesis. In the SOFA 24 h group we found a significant positive correlation between glucose and HbA1c levels, significant negative correlations between white blood cell count and glucose, white blood cell count and HbA1c. We also found a significant positive correlation between length of hospital stay and HbA1c levels in survivors. A significant negative correlation was observed between white blood cell count and HbA1c in SOFA 24 h diabetic, septic patients similarly to the SIRS 24 h group. However as white blood cell count is not a SOFA criterium this correlation and therefore the possible early diagnostic potential of HbA1c is not that significant in SOFA patients. On the other hand - as there was a significant positive correlation between length of hospital and HbA1c levels in survivors - HbA1c may be a significant prognostic tool in diabetic, septic patients in whom the diagnosis is based on the SOFA criteria. We did not find any significant correlation in SIRS 30d patients. Previous studies found no significant difference between HbA1c levels measured on admission and 30 days earlier in critically ill patients ( 41 ). Based on this the same correlations we found in SIRS 24 h patients should have been observed in SIRS 30d patients. A possible explanation for this difference is that HbA1c in our study was measured within 30 days prior to these patient’s emergency department admission, and not 30 days prior exactly, and HbA1c measured on admission correlates better with glucose concentration of the previous weeks. We did not find any significant correlation in the SOFA 30d group either. Some limitations must be noted. Despite our significant correlations, enrolment of a larger population might increase the statistical power. Additionally, HbA1c levels strongly depend on the turnover of red blood cells: slow turnover (e.g. iron, vitamin B12, or folate deficiency anemias) often results in higher, whereas fast turnover (e.g. hemolytic anemia. erythropoietin therapy) in lower HbA1c levels ( 30 – 37 ). Due to metabolic changes and erythropoietin treatment in patients with end-stage renal failure HbA1c levels are often altered ( 30 , 32 – 37 ). Therefore, all patients with the above mentioned disorders have been excluded from the study. Furthermore, according to some studies HbA1c levels vary among different racial and ethnic groups (higher levels in Afro-Americans and Asians). ( 37 ). We enrolled only Caucasian patients. Conclusion Based on our results we can conclude that even normal white blood cell count could be abnormal in diabetic, septic patients in whom the diagnosis is based on the SIRS criteria if an elevated HbA1c level is measured within 24 hours after admission (preferably upon arrival). Therefore, in these patients normal white blood cell count (4–12 × 10 9 /l) with elevated HbA1c levels could be considered a positive SIRS criterium. In diabetic, septic patients, in whom the diagnosis of sepsis is based on the SOFA score and HbA1c is measured within 24 hours after admission (preferably upon arrival), HbA1c could be an important prognostic tool as there is a significant positive correlation between HbA1c levels and lenght of hospital stay in survivors. Futher studies focusing on the possible diagnostic and prognostic role of HbA1c in diabetic, septic patients are needed to verify our data. Methods We collected all cases from the Department of Emergency Medicine and later Emergency Clinic at the University of Debrecen, between 1st January 2017 and 31st December 2018 (27737 patients, 42766 cases). First, we selected patients who had their HbA1c measured in the study period (3743 patients) and later from these patients we collected those diabetic, septic patients who had HbA1c levels measured either in the previous 30 days or within 24 hours after their Emergency Department admission. Sepsis was diagnosed based on the SIRS criteria. Patients with autoimmune disease, end-stage renal failure, liver cirrhosis and active cancer were excluded from our study. As HbA1c levels highly depend on the turnover of red blood cells, patients with iron, vitamin B12, and folate deficiency anemias were also excluded. Exclusion criteria also included erythropoietin therapy and hemolytic anemia for the previous reason. This way 112 diabetic, septic patients were included in our study (SIRS group) from whom 39 had HbA1c measured in the previous 30 days (SIRS 30d subgroup) and 73 within 24 hours after their Emergency Department admission (SIRS 24 h subgroup). The past medical history (type of diabetes mellitus and date of diagnosis, hypertension, dyslipidemia, ischemic heart disease, previous myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting surgery, transient ischemic attack, stroke, peripheral arterial disease, chronic renal failure), anti-diabetic therapy (metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, other oral anti-diabetic agents, insulin), laboratory results (arterial blood gas results, urea and electrolytes, glucose levels, liver function tests, pancreatic enzymes, C-reactive protein - CRP, procalcitonin - PCT, albumin, full blood count), HbA1c levels and time of measurement, SIRS and SOFA scores, microbiological results, type of infection, length of hospital stay and mortality data of all patients were collected. Most laboratory parameters - with sometimes the exception of HbA1c - were measured upon arrival. We later selected those patients from the SIRS group, whose SOFA score was ≥ 2 (55 patients, SOFA group). Patients from the SOFA group were also divided into subgroups based on the time of measurement of HbA1c (patients with HbA1c measured in the previous 30 days - SOFA 30d subgroup vs. patients with HbA1c measured within 24 hours after their Emergency Department admission - SOFA 24 h subgroup) (Fig. 1 .) The STATISTICA 13.7 (TIBCO INC. USA) software was used for data analysis. Results were either given as mean +/- standard deviation or median (lower and upper quartile), respectively. We used Pearson’s correlation for finding significant relationships (in case of significant correlations p was < 0.05). Abbreviations CRP: C-reactive protein HbA1c: hemoglobin A1c MAP: mean arterial pressure PCT: procalcitonin qSOFA: quick SOFA SIRS: Systemic Inflammatory Response Syndrome SOFA: Sequential Organ Failure Assessment WBC: white blood cell count Declarations Ethics approval and consent to participate The work is conform to the guiding principles of the Declaration of Helsinki, and our study subjects gave informed consent of a study that has been approved by the Institutional Committee on Human Research at our institution. Consent for publication Not applicable. Availability of data and materials All data generated or analyzed during this study are included in this published article. All data generated or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests The authors report no conflict of interest. Funding The work is supported by the National Research, Development and Innovation Office – NKFIH, grant number: K115723 and by the GINOP-2.3.2-15-2016-00005 project. The GINOP project is co-financed by the European Union under the European Regional Development Fund. Authors' contributions Design: I. Juhász, G. Paragh Collection of data: I. Juhász, J. Juhász, L. Végh, S. Ujfalusi Analysis and/or interpretation of data: H. Lőrincz, I. Seres Writing (not revising) all or sections of the manuscript: I. Juhász, M. Harangi Manuscript review: G. Paragh, Z. Szabó Acknowledgements The authors are also thankful for the contribution of Lilla Kovács, Tünde Adamecz, Árpád Badics and Tamás Tornai in this study. References American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20(6):864-74. 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Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. BMJ. 2018;362:k1497. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26(3-4):259-65. Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study. Diabetes Care. 2018;41(3):513-21. Fahey TJ, Sadaty A, Jones WG, Barber A, Smoller B, Shires GT. Diabetes impairs the late inflammatory response to wound healing. J Surg Res. 1991;50(4):308-13. Grossmann V, Schmitt VH, Zeller T, Panova-Noeva M, Schulz A, Laubert-Reh D, et al. Profile of the Immune and Inflammatory Response in Individuals With Prediabetes and Type 2 Diabetes. Diabetes Care. 2015;38(7):1356-64. Estrada CA, Young JA, Nifong LW, Chitwood WR. Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting. Ann Thorac Surg. 2003;75(5):1392-9. Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial. Diabetes Care. 2002;25(2):275-8. Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia. 2007;50(11):2239-44. Panzer S, Kronik G, Lechner K, Bettelheim P, Neumann E, Dudczak R. Glycosylated hemoglobins (GHb): an index of red cell survival. Blood. 1982;59(6):1348-50. Brown JN, Kemp DW, Brice KR. Class effect of erythropoietin therapy on hemoglobin A(1c) in a patient with diabetes mellitus and chronic kidney disease not undergoing hemodialysis. Pharmacotherapy. 2009;29(4):468-72. Ng JM, Cooke M, Bhandari S, Atkin SL, Kilpatrick ES. The effect of iron and erythropoietin treatment on the A1C of patients with diabetes and chronic kidney disease. Diabetes Care. 2010;33(11):2310-3. Roberts WL, Safar-Pour S, De BK, Rohlfing CL, Weykamp CW, Little RR. Effects of hemoglobin C and S traits on glycohemoglobin measurements by eleven methods. Clin Chem. 2005;51(4):776-8. Saaddine JB, Fagot-Campagna A, Rolka D, Narayan KM, Geiss L, Eberhardt M, et al. Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey. Diabetes Care. 2002;25(8):1326-30. Herman WH, Ma Y, Uwaifo G, Haffner S, Kahn SE, Horton ES, et al. Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care. 2007;30(10):2453-7. Kaneto H. Pancreatic β-cell glucose toxicity in type 2 diabetes mellitus. Curr Diabetes Rev. 2015;11(1):2-6. Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52(3):581-7. Hall E, Dekker Nitert M, Volkov P, Malmgren S, Mulder H, Bacos K, et al. The effects of high glucose exposure on global gene expression and DNA methylation in human pancreatic islets. Mol Cell Endocrinol. 2018;472:57-67. Luethi N, Cioccari L, Tanaka A, Kar P, Giersch E, Deane AM, et al. Glycated Hemoglobin A1c Levels Are Not Affected by Critical Illness. Crit Care Med. 2016;44(9):1692-4. Supplementary Files GraphicalabstractIJEM.jpg Cite Share Download PDF Status: Published Journal Publication published 18 Mar, 2022 Read the published version in Emergency Medicine International → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-127448","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Original Research","associatedPublications":[],"authors":[{"id":6350349,"identity":"f1e37384-c88e-4704-8ffe-49da99fa7169","order_by":0,"name":"Imre Juhász","email":"","orcid":"","institution":"University of Debrecen Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Imre","middleName":"","lastName":"Juhász","suffix":""},{"id":6350350,"identity":"5146fe44-260a-4330-b3ba-6c746ebebe1a","order_by":1,"name":"Janka Juhász","email":"","orcid":"","institution":"University of Debrecen Faculty of Medicine: Debreceni Egyetem Altalanos Orvostudomanyi Kar","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Janka","middleName":"","lastName":"Juhász","suffix":""},{"id":6350351,"identity":"28b690a2-5735-4b99-8712-7e711b060fbc","order_by":2,"name":"Hajnalka Lőrincz","email":"","orcid":"","institution":"University of Debrecen Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hajnalka","middleName":"","lastName":"Lőrincz","suffix":""},{"id":6350352,"identity":"712d40aa-dd38-4bbc-800a-e38d3ea88610","order_by":3,"name":"Ildikó Seres","email":"","orcid":"","institution":"University of Debrecen Faculty of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ildikó","middleName":"","lastName":"Seres","suffix":""},{"id":6350353,"identity":"9dda0241-fdc4-422a-8536-4311a2eabe51","order_by":4,"name":"Lilla Végh","email":"","orcid":"","institution":"University of Debrecen Faculty of 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of Medicine: Debreceni Egyetem Altalanos Orvostudomanyi Kar","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zoltán","middleName":"","lastName":"Szabó","suffix":""},{"id":6350357,"identity":"e8c88c8c-ebe2-467a-9dd7-15a67d5544cc","order_by":8,"name":"György Paragh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6ElEQVRIiWNgGAWjYLACxgabBAZ2NsYDCQwSBsRqSUtgYGZjIEnLYYgWIJuwFnP2sw8/ft1xPo+fmS3hwMMdFsb8DcwPH93Ao8WyJ91YWvbM7WLJZrYDBxLPSJhJHGAzNs7Bo8XgQBqDtGTb7cQNh9kbDiS2SdgwHOBhk8ar5fwz5t+SbecS98O0yBPUciONTfJj24HEDcwgh7VJmBkQ0mI54xmbNWNbcrHEYaD3gVqMDQ8T8Is5fxrzzZ9tdnn87W2GD3+21RnOO9788DFehwExMw+KEDMe5TAtjD8IKBoFo2AUjIIRDgD4WU7gQFFz+AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-6791-3870","institution":"University of Debrecen Faculty of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"György","middleName":"","lastName":"Paragh","suffix":""}],"badges":[],"createdAt":"2020-12-12 20:03:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-127448/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-127448/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1155/2022/8543232","type":"published","date":"2022-03-18T20:02:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":4306634,"identity":"bc56d49e-90e9-4383-ab25-11738261a1a3","added_by":"auto","created_at":"2020-12-16 16:51:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":293740,"visible":true,"origin":"","legend":"Flowchart showing the structure of the study, enrollment and evaluation procedure, and how the patients were divided into the groups, and phases.","description":"","filename":"Onlinefig1HbA1c.Png","url":"https://assets-eu.researchsquare.com/files/rs-127448/v1/fd356997e07e4c2caaaaec66.Png"},{"id":4306635,"identity":"19510469-8aa1-473f-869e-a2638de6d505","added_by":"auto","created_at":"2020-12-16 16:51:58","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":305150,"visible":true,"origin":"","legend":"Correlations between glucose and HbA1C (%) (a), glucose and white blood cell count (b), white blood cell count and HbA1C (%) in diabetic, SIRS 24h septic patients (n=73)","description":"","filename":"Onlinefig2HbA1c.Png","url":"https://assets-eu.researchsquare.com/files/rs-127448/v1/a6c9f7373f103daadc62eddf.Png"},{"id":4306636,"identity":"2053e117-82b7-44eb-ac14-0af76cefdd68","added_by":"auto","created_at":"2020-12-16 16:51:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":201581,"visible":true,"origin":"","legend":"Correlations between glucose and HbA1C (%) (a), glucose and white blood cell count (b), white blood cell and HbA1C (%) in diabetic, SOFA 24h septic patients (n=34)","description":"","filename":"Onlinefig3HbA1c.Png","url":"https://assets-eu.researchsquare.com/files/rs-127448/v1/3d510855ea65e87d0bb6888c.Png"},{"id":19702522,"identity":"1a030b61-7c83-4cf3-a9de-ef4a59dd484a","added_by":"auto","created_at":"2022-03-28 20:04:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":842083,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-127448/v1/9231f3d9-dfa2-4435-8c58-295a3f2fe748.pdf"},{"id":4306637,"identity":"54317d96-149e-45f9-b6c6-80255d73695e","added_by":"auto","created_at":"2020-12-16 16:51:59","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":112583,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalabstractIJEM.jpg","url":"https://assets-eu.researchsquare.com/files/rs-127448/v1/4947058ea6c89422141dcbcb.jpg"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe Potential Diagnostic and Predictive Role of HbA1c in Diabetic, Septic Patients - a Retrospective Single Center Study\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eSepsis is a potentially life-threatening condition. Its definition keeps on changing as we learn more and more about the underlying pathomechanism of the disease. Before 2016 the Systemic Inflammatory Response Syndrome (SIRS) criteria was used for the diagnosis of sepsis: if at least 2 out of 4 clinical findings were present in a patient with a likely infection the diagnsosis of sepsis was confirmed. The SIRS criteria are the following: tachycardia (heart rate\u0026thinsp;\u0026gt;\u0026thinsp;90), hypothermia/fever (temperature\u0026thinsp;\u0026lt;\u0026thinsp;36\u0026nbsp;\u0026deg;C or \u0026gt;\u0026thinsp;38\u0026nbsp;\u0026deg;C), hyperventilation/hypocapnia (respiratory rate\u0026thinsp;\u0026gt;\u0026thinsp;20 or PaCO₂ \u0026lt; 32\u0026nbsp;mmHg), leukopenia/leukocytosis (white blood cell count\u0026thinsp;\u0026lt;\u0026thinsp;4,000/mm\u0026sup3; or \u0026gt;\u0026thinsp;12,000/mm\u0026sup3; or \u0026gt;\u0026thinsp;10% bands). The definition distinguished sepsis, severe sepsis and septic shock (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). In 2016 the definition of sepsis changed once again: the SIRS criteria as well as the definition of severe sepsis were no longer recommended. According to the new definition sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The Sequential Organ Failure Assessment (SOFA) and the quick SOFA (qSOFA) scores have been introduced (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). The diagnostic algorithm of sepsis has changed: in a patient with a likely infection the use of the quick SOFA score is recommended (it consists of 3 components: systolic blood pressure\u0026thinsp;\u0026le;\u0026thinsp;100\u0026nbsp;mmHg, altered mental status, respiratory rate\u0026thinsp;\u0026ge;\u0026thinsp;22). According to the new recommendations a positive qSOFA Score (\u0026ge;\u0026thinsp;2 points) should prompt the calculation of the SOFA score to confirm the diagnosis of sepsis. If the qSOFA score is negative (\u0026lt;\u0026thinsp;2 points) but sepsis is still likely, we should also calculate the SOFA score. In a patient with a negative qSOFA score (\u0026lt;\u0026thinsp;2 points) and an unlikely infection, sepsis can be excluded. If a patient\u0026rsquo;s SOFA score is \u0026ge;\u0026thinsp;2 the diagnosis of sepsis is confirmed. The SOFA score consists of the following: platelet count, bilirubin and creatinine levels, mean arterial pressure (MAP) or administration of vasoactive agents, altered mental status (based on the Glasgow Coma Scale) and PaO2/FiO2. Septic shock is a form of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by vasopressor requirement to maintain a MAP of 65\u0026nbsp;mmHg or greater and serum lactate levels greater than 2\u0026nbsp;mmol/L in the absence of hypovolemia (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Lots of studies have been published since 2016 in which the SIRS, qSOFA and SOFA criteria have been compared and data are controversial (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Some results have shown inferior sensitivity of the qSOFA score compared to the previously favored SIRS criteria in the diagnosis of sepsis (\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Partly due to this, the 2016 recommendations are not universally accepted, and many countries still favor the previous diagnostic criteria and therefore the SIRS criteria.\u003c/p\u003e \u003cp\u003eSepsis is usually bacterial in origin (caused mainly by Gram positive bacteria), however viral and fungal causes could also be in the background (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Its global incidence is increasing, and it can be as high as 437/100000/year (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Major risk factors of sepsis include: advanced age (\u0026ge;\u0026thinsp;65\u0026nbsp;years), previous hospitalization (especially in the previous 90 days, intensive care unit admission, nosocomial infections, community-acquired pneumonia), immunosuppression (e.g. neoplasms, renal failure, liver failure, AIDS, splenectomy) and genetic factors (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17 CR18 CR19 CR20 CR21 CR22\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Diabetes mellitus, a metabolic disorder which has become a global health burden partly due to its rising incidence, is another major risk factor for sepsis (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Immune response is severely altered in diabetics: neutrophil chemotaxis, phagocytosis, intracellular bactericide activity, opsonization as well as cell-mediated immunity are all affected (\u003cspan additionalcitationids=\"CR26 CR27 CR28\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Therefore, infections are more common in diabetics compared to non-diabetic individuals. Poor glycemic control and hyperglycemia further increases the chance of infections in diabetics (\u003cspan additionalcitationids=\"CR26 CR27 CR28\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHemoglobin in newly formed red blood cells is minimally glycated. The membrane of circulating red blood cells is permeable to glucose therefore it could be irreversibly attached to hemoglobin in a non-enzymatic way. HbA1c gives us information regarding mean blood glucose concentration over the lifespan of red blood cells (120 days) and its value correlates best with mean blood sugar levels over the previous 8\u0026ndash;12 weeks. HbA1c is widely used nowadays to diagnose diabetes and monitor carbohydrate metabolism in diabetics (\u003cspan additionalcitationids=\"CR31 CR32 CR33 CR34 CR35 CR36\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e), however its potential role in diabetic, septic patients has not yet been studied.\u003c/p\u003e "},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eDiabetic, septic patients with HbA1c levels measured within 24 hours after emergency department admission\u003c/h2\u003e\n\u003cdiv id=\"Sec4\" class=\"Section3\"\u003e\n\u003ch2\u003eSIRS 24\u0026nbsp;h patients\u003c/h2\u003e\n\u003cp\u003eSIRS 24\u0026nbsp;h patients were 72.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u0026nbsp;years old (73 patients, 47 females, 26 males). All our patients were type II diabetics. Anthropometric data, past medical history, anti-diabetic therapy, laboratory parameters of patients as well as length of hospital stay in survivors were summarized in a table (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). We analyzed the relationship between laboratory parameters and HbA1c as well as the correlation between length of hospital stay and HbA1c. Additionally we examined the relationship between leukocyte count and glucose, platelet count and glucose, and length of hospital stay and glucose levels. (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.). In these patients there was a significant positive correlation between glucose and HbA1c levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e/a). We found significant negative correlations between white blood cell count and glucose (p\u0026thinsp;=\u0026thinsp;0.01) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e/b), white blood cell count and HbA1c levels (p\u0026thinsp;=\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e/c). The same correlations were observed in most cases even if patients were divided based on gender, anti-diabetic therapy (oral anti-diabetic agents vs. insulin therapy), age (\u0026lt;\u0026thinsp;65 yrs vs.\u0026ge;65 yrs) and hospitalization in the previous 90\u0026nbsp;days (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eAnthropometric data, anti-diabetic therapy and laboratory parameters of diabetic, SIRS 24\u0026nbsp;h and SOFA 24\u0026nbsp;h septic patients. Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (lower-upper quartile).\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003eDiabetic, septic patients\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eCriteria\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSIRS 24\u0026nbsp;h group\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eSOFA 24\u0026nbsp;h group\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNumber of patients (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73 (47f/26\u0026nbsp;m)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34 (21f/13\u0026nbsp;m)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (years)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72.8\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73.9\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eType 2 diabetes (n)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eComorbidities\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e67 (91.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31 (91.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDyslipidemia (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31 (42.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (35.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIHD/AMI/PCI/CABG (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e32 (43.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (52.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTIA/stroke (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (20.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (17.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePeripheral arterial disease (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42 (57.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (52.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eChronic kidney disease (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (37.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e13 (38.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eAnti-diabetic medications\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMetformin (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30 (41.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (32.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSulphonyl urea (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (32.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (29.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDPP4 (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (5.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eInsulin (n; %)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (24.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (32.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"3\" align=\"left\"\u003e\n\u003cp\u003e\u003cstrong\u003eLaboratory parameters\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlucose (mmol/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.5 (7.7\u0026ndash;16.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.05 (8.5\u0026ndash;19.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHbA1C (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eUrea (mmol/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.4 (6-12.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9.85 (6.2\u0026ndash;19.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCreatinine (\u0026micro;mol/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e99 (77\u0026ndash;137)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e118 (95\u0026ndash;172)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGlomerular filtration rate (ml/min*1.73\u0026nbsp;m2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e52 (38\u0026ndash;75)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42 (27\u0026ndash;61)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eC-reactive protein (mg/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e77 (21-151.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e108 (21.3-246.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAST (U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (17-33.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25 (16\u0026ndash;42)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGGT (U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e35 (21\u0026ndash;69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (16\u0026ndash;124)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eALT (U/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (14\u0026ndash;32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (14\u0026ndash;37)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal bilirubin (\u0026micro;mol/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (6.5\u0026ndash;17.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.2 (6.3\u0026ndash;33.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eWhite blood cell count (G/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRed blood cell count (T/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemoglobin concentration (g/l)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e129.8\u0026thinsp;\u0026plusmn;\u0026thinsp;22.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e133.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.4\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eThrombocyte (G/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e252.6\u0026thinsp;\u0026plusmn;\u0026thinsp;76.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e251.0\u0026thinsp;\u0026plusmn;\u0026thinsp;92.8\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLength of hospital stay (day)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (6-11.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (7-11.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCorrelations between various laboratory parameters in subgroups of diabetic, SIRS 24\u0026nbsp;h septic patients. Abbreviations: CRP, C-reactive protein; HbA1c, hemoglobin A1c; LOS, length of stay in survivors; RBC, red blood cell; THR, thrombocyte; WBC, white blood cell.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eglucose vs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eurea\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ecreatinine\u003c/p\u003e\n\u003cp\u003evs.\u003c/p\u003e\n\u003cp\u003eHbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCRP\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ebilirubin\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003cp\u003evs. glucose\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRBC\u003c/p\u003e\n\u003cp\u003evs. glucose\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRBC\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTHR\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLOS\u003c/p\u003e\n\u003cp\u003evs.\u003c/p\u003e\n\u003cp\u003eHbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLOS\u003c/p\u003e\n\u003cp\u003evs. glucose\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLOS\u003c/p\u003e\n\u003cp\u003evs.\u003c/p\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAll\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e73\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.74\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.29\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.37\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003emales\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.84\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.43\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.48\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.46\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003efemales\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.70\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.28\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.32\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enon-insulin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.76\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.28\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.35\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003einsulin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e18\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.69\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.52\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.57\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eunder\u003c/p\u003e\n\u003cp\u003e65 yrs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.87\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.53\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eover\u003c/p\u003e\n\u003cp\u003e65 yrs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e56\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.70\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.28\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.33\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot stay within 90 days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e66\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.77\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.32\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.38\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStay within 90 days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eSOFA 24\u0026nbsp;h patients\u003c/h2\u003e\n\u003cp\u003e34 type II diabetic, septic patients were in the SOFA 24\u0026nbsp;h group (21 females, 13 males, age: 74\u0026thinsp;\u0026plusmn;\u0026thinsp;12.3\u0026nbsp;years). Anthropometric data, past medical history, anti-diabetic therapy, laboratory parameters of patients as well as length of hospital stay in survivors were summarized in a table (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). We also analyzed the relationship between laboratory parameters and HbA1c as well as the correlation between length of hospital stay and HbA1c. Additionally we examined the relationship between leukocyte count and glucose, platelet count and glucose, and length of hospital stay and glucose levels. There was a significant positive correlation between glucose and HbA1c levels in the SOFA 24\u0026nbsp;h group, similarly to the one we found in SIRS 24\u0026nbsp;h patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e/a). We also found significant negative correlations between white blood cell count and glucose (p\u0026thinsp;=\u0026thinsp;0.02) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e/b) and white blood cell count and HbA1c levels in SOFA 24\u0026nbsp;h patients (p\u0026thinsp;=\u0026thinsp;0.02) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e/c). Additionally, there was a significant positive correlation between HbA1c levels and length of hospital stay in survivors (p\u0026thinsp;=\u0026thinsp;0.01) (data not shown). The previous correlations in the SOFA 24\u0026nbsp;h group were observed in most cases even if patients were divided based on gender, anti-diabetic therapy (oral anti-diabetic agents vs. insulin therapy), age (\u0026lt;\u0026thinsp;65 yrs vs.\u0026ge;65 yrs) and hospitalization in the previous 90\u0026nbsp;days (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eCorrelations between various laboratory parameters in subgroups of diabetic, SOFA 24\u0026nbsp;h septic patients. Abbreviations: CRP, C-reactive protein; HbA1c, hemoglobin A1c; LOS, length of stay in survivors; RBC, red blood cell; THR, thrombocyte; WBC, white blood cell.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003en\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eglucose vs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eurea\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ecreatinine\u003c/p\u003e\n\u003cp\u003evs.\u003c/p\u003e\n\u003cp\u003eHbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCRP\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ebilirubin\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003cp\u003evs. glucose\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRBC\u003c/p\u003e\n\u003cp\u003evs. glucose\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eRBC\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eTHR\u003c/p\u003e\n\u003cp\u003evs. HbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLOS\u003c/p\u003e\n\u003cp\u003evs.\u003c/p\u003e\n\u003cp\u003eHbA1c\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLOS\u003c/p\u003e\n\u003cp\u003evs. glucose\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eLOS\u003c/p\u003e\n\u003cp\u003evs.\u003c/p\u003e\n\u003cp\u003eWBC\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAll\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e34\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.80\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.39\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.41\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.45\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.57\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003emales\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.95\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.59\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.62\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003efemales\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.73\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.58\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.72\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enon-insulin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.82\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.42\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.44\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.56\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.43\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003einsulin\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.79\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.67\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.04\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.65\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.05\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eunder\u003c/p\u003e\n\u003cp\u003e65 yrs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.84\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.80\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.82\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.91\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eover\u003c/p\u003e\n\u003cp\u003e65 yrs\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.80\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.45\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.55\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.004\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNot stay within 90 days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.80\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.43\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.02\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er=-0.41\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.03\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.62\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.73\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStay within 90 days\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003er\u0026thinsp;=\u0026thinsp;0.96\u003c/p\u003e\n\u003cp\u003ep\u0026thinsp;=\u0026thinsp;0.01\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ens\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003ch2\u003eDiabetic, septic patients with HbA1c levels measured in the previous 30 days before their emergency department admission\u003c/h2\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eSIRS 30d and SOFA 30d patients\u003c/h2\u003e\n\u003cp\u003eThere were 39 diabetic, septic patients in the SIRS 30d group. We studied the same correlations that were previously examined in the SIRS 24\u0026nbsp;h group. We did not find any significant correlation in this population even if we later selected and examined patients whose SOFA score was positive (\u0026ge;\u0026thinsp;2) (SOFA 30d group, 21 patients) (data not shown).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":" \u003cp\u003eThis is the first study to evaluate the potential role of HbA1c in diabetic, septic patients. In SIRS 24\u0026nbsp;h patients we found a significant positive correlation between glucose and HbA1c levels, while significant negative correlations were observed between white blood cell count and glucose, white blood cell count and HbA1c. Correlations were observed even if patients were divided based on gender, anti-diabetic therapy (oral anti-diabetic agents vs. insulin therapy), age (\u0026lt;\u0026thinsp;65 yrs vs.\u0026ge;65 yrs) and hospitalization in the previous 90 days. One possible explanation behind the observed negative correlations between white blood cell count and glucose, white blood cell count and HbA1c is glucose toxicity, a phenomenon previously described in pancreatic beta cells (\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). According to previous studies, hyperglycemia in diabetic patients increases oxidative stress and induces glucose-induced apoptosis mainly in metabolically active cells (e.g. white blood cells in sepsis), resulting in cell death. There are some diabetic, septic patients - in whom sepsis is diagnosed based on the SIRS criteria - whose white blood cell count is normal, despite being septic. These diabetic, septic patients with normal white blood cell counts (WBC count between 4\u0026ndash;12\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/l) have higher HbA1c levels. This observation is crucial as white blood cell count is an important part of the SIRS criteria (positive criterium: white blood cell count\u0026thinsp;\u0026lt;\u0026thinsp;4,000/mm\u0026sup3; or \u0026gt;\u0026thinsp;12,000/mm\u0026sup3; or \u0026gt;\u0026thinsp;10% bands). It may occur in diabetic, septic patients - in whom diagnosis is based on the SIRS criteria - that white blood cell count is normal (between 4\u0026ndash;12\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/l) and there is only one other positive SIRS criterium (heart rate\u0026thinsp;\u0026gt;\u0026thinsp;90, temperature\u0026thinsp;\u0026lt;\u0026thinsp;36\u0026nbsp;\u0026deg;C or \u0026gt;\u0026thinsp;38\u0026nbsp;\u0026deg;C, respiratory rate\u0026thinsp;\u0026gt;\u0026thinsp;20 or PaCO₂ \u0026lt; 32\u0026nbsp;mmHg). According to the definition of sepsis - based on the SIRS criteria - these patients are not septic however the potential life-threatening immune processes might have already started. HbA1c - based on the negative correlation found between white blood cell count and HbA1c levels - can be a useful tool in finding these patients: in diabetic patients, normal white blood cell count (4\u0026ndash;12\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/l) with elevated HbA1c levels should be considered a positive SIRS criterium. Therefore HbA1c \u0026ndash; measured within 24 hours after admission (preferably upon arrival) - could turn out to be an efficient way to identify these diabetic, septic patients early and initiate sepsis treatment accordingly. Further, large, multi-centric studies are needed to confirm our hypothesis.\u003c/p\u003e \u003cp\u003eIn the SOFA 24\u0026nbsp;h group we found a significant positive correlation between glucose and HbA1c levels, significant negative correlations between white blood cell count and glucose, white blood cell count and HbA1c. We also found a significant positive correlation between length of hospital stay and HbA1c levels in survivors. A significant negative correlation was observed between white blood cell count and HbA1c in SOFA 24\u0026nbsp;h diabetic, septic patients similarly to the SIRS 24\u0026nbsp;h group. However as white blood cell count is not a SOFA criterium this correlation and therefore the possible early diagnostic potential of HbA1c is not that significant in SOFA patients. On the other hand - as there was a significant positive correlation between length of hospital and HbA1c levels in survivors - HbA1c may be a significant prognostic tool in diabetic, septic patients in whom the diagnosis is based on the SOFA criteria.\u003c/p\u003e \u003cp\u003eWe did not find any significant correlation in SIRS 30d patients. Previous studies found no significant difference between HbA1c levels measured on admission and 30 days earlier in critically ill patients (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e). Based on this the same correlations we found in SIRS 24\u0026nbsp;h patients should have been observed in SIRS 30d patients. A possible explanation for this difference is that HbA1c in our study was measured within 30 days prior to these patient\u0026rsquo;s emergency department admission, and not 30 days prior exactly, and HbA1c measured on admission correlates better with glucose concentration of the previous weeks. We did not find any significant correlation in the SOFA 30d group either.\u003c/p\u003e \u003cp\u003eSome limitations must be noted. Despite our significant correlations, enrolment of a larger population might increase the statistical power. Additionally, HbA1c levels strongly depend on the turnover of red blood cells: slow turnover (e.g. iron, vitamin B12, or folate deficiency anemias) often results in higher, whereas fast turnover (e.g. hemolytic anemia. erythropoietin therapy) in lower HbA1c levels (\u003cspan additionalcitationids=\"CR31 CR32 CR33 CR34 CR35 CR36\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Due to metabolic changes and erythropoietin treatment in patients with end-stage renal failure HbA1c levels are often altered (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan additionalcitationids=\"CR33 CR34 CR35 CR36\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Therefore, all patients with the above mentioned disorders have been excluded from the study. Furthermore, according to some studies HbA1c levels vary among different racial and ethnic groups (higher levels in Afro-Americans and Asians). (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). We enrolled only Caucasian patients.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eBased on our results we can conclude that even normal white blood cell count could be abnormal in diabetic, septic patients in whom the diagnosis is based on the SIRS criteria if an elevated HbA1c level is measured within 24 hours after admission (preferably upon arrival). Therefore, in these patients normal white blood cell count (4\u0026ndash;12\u0026thinsp;\u0026times;\u0026thinsp;10\u003csup\u003e9\u003c/sup\u003e/l) with elevated HbA1c levels could be considered a positive SIRS criterium.\u003c/p\u003e \u003cp\u003eIn diabetic, septic patients, in whom the diagnosis of sepsis is based on the SOFA score and HbA1c is measured within 24 hours after admission (preferably upon arrival), HbA1c could be an important prognostic tool as there is a significant positive correlation between HbA1c levels and lenght of hospital stay in survivors.\u003c/p\u003e \u003cp\u003eFuther studies focusing on the possible diagnostic and prognostic role of HbA1c in diabetic, septic patients are needed to verify our data.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003eWe collected all cases from the Department of Emergency Medicine and later Emergency Clinic at the University of Debrecen, between 1st January 2017 and 31st December 2018 (27737 patients, 42766 cases). First, we selected patients who had their HbA1c measured in the study period (3743 patients) and later from these patients we collected those diabetic, septic patients who had HbA1c levels measured either in the previous 30 days or within 24 hours after their Emergency Department admission. Sepsis was diagnosed based on the SIRS criteria. Patients with autoimmune disease, end-stage renal failure, liver cirrhosis and active cancer were excluded from our study. As HbA1c levels highly depend on the turnover of red blood cells, patients with iron, vitamin B12, and folate deficiency anemias were also excluded. Exclusion criteria also included erythropoietin therapy and hemolytic anemia for the previous reason. This way 112 diabetic, septic patients were included in our study (SIRS group) from whom 39 had HbA1c measured in the previous 30 days (SIRS 30d subgroup) and 73 within 24 hours after their Emergency Department admission (SIRS 24\u0026nbsp;h subgroup). The past medical history (type of diabetes mellitus and date of diagnosis, hypertension, dyslipidemia, ischemic heart disease, previous myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting surgery, transient ischemic attack, stroke, peripheral arterial disease, chronic renal failure), anti-diabetic therapy (metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, other oral anti-diabetic agents, insulin), laboratory results (arterial blood gas results, urea and electrolytes, glucose levels, liver function tests, pancreatic enzymes, C-reactive protein - CRP, procalcitonin - PCT, albumin, full blood count), HbA1c levels and time of measurement, SIRS and SOFA scores, microbiological results, type of infection, length of hospital stay and mortality data of all patients were collected. Most laboratory parameters - with sometimes the exception of HbA1c - were measured upon arrival.\u003c/p\u003e \u003cp\u003eWe later selected those patients from the SIRS group, whose SOFA score was \u0026ge;\u0026thinsp;2 (55 patients, SOFA group). Patients from the SOFA group were also divided into subgroups based on the time of measurement of HbA1c (patients with HbA1c measured in the previous 30 days - SOFA 30d subgroup vs. patients with HbA1c measured within 24 hours after their Emergency Department admission - SOFA 24\u0026nbsp;h subgroup) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.)\u003c/p\u003e \u003cp\u003eThe STATISTICA 13.7 (TIBCO INC. USA) software was used for data analysis. Results were either given as mean +/- standard deviation or median (lower and upper quartile), respectively. We used Pearson\u0026rsquo;s correlation for finding significant relationships (in case of significant correlations p was \u0026lt;\u0026thinsp;0.05).\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eCRP: C-reactive protein\u003c/p\u003e\n\u003cp\u003eHbA1c: hemoglobin A1c\u003c/p\u003e\n\u003cp\u003eMAP: mean arterial pressure\u003c/p\u003e\n\u003cp\u003ePCT: procalcitonin\u003c/p\u003e\n\u003cp\u003eqSOFA: quick SOFA\u003c/p\u003e\n\u003cp\u003eSIRS: Systemic Inflammatory Response Syndrome\u003c/p\u003e\n\u003cp\u003eSOFA: Sequential Organ Failure Assessment\u003c/p\u003e\n\u003cp\u003eWBC: white blood cell count\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work is conform to the guiding principles of the Declaration of Helsinki, and our study subjects gave informed consent of a study that has been approved by the Institutional Committee on Human Research at our institution.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article. All data generated or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe work is supported by the National Research, Development and Innovation Office \u0026ndash;\u0026nbsp;NKFIH, grant number: K115723 and by the GINOP-2.3.2-15-2016-00005 project.\u003c/p\u003e\n\u003cp\u003eThe GINOP project is co-financed by the European Union under the European Regional Development Fund.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDesign: I. Juh\u0026aacute;sz, G. Paragh\u003c/p\u003e\n\u003cp\u003eCollection of data: I. Juh\u0026aacute;sz, J. Juh\u0026aacute;sz, L. V\u0026eacute;gh, S. Ujfalusi\u003c/p\u003e\n\u003cp\u003eAnalysis and/or interpretation of data: H. Lőrincz, I. Seres\u003c/p\u003e\n\u003cp\u003eWriting (not revising) all or sections of the manuscript: I. Juh\u0026aacute;sz, M. Harangi\u003c/p\u003e\n\u003cp\u003eManuscript review: G. Paragh, Z. Szab\u0026oacute;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors are also thankful for the contribution of Lilla Kov\u0026aacute;cs, T\u0026uuml;nde Adamecz, \u0026Aacute;rp\u0026aacute;d Badics and Tam\u0026aacute;s Tornai in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmerican College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. 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Hospitalization Type and Subsequent Severe Sepsis. Am J Respir Crit Care Med. 2015;192(5):581-8.\u003c/li\u003e\n\u003cli\u003eNetea MG, van der Meer JW. Immunodeficiency and genetic defects of pattern-recognition receptors. N Engl J Med. 2011;364(1):60-70.\u003c/li\u003e\n\u003cli\u003eVincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH, et al. The prevalence of nosocomial infection in intensive care units in Europe. Results of the European Prevalence of Infection in Intensive Care (EPIC) Study. EPIC International Advisory Committee. JAMA. 1995;274(8):639-44.\u003c/li\u003e\n\u003cli\u003eFalagas ME, Kompoti M. Obesity and infection. Lancet Infect Dis. 2006;6(7):438-46.\u003c/li\u003e\n\u003cli\u003eWilliams MD, Braun LA, Cooper LM, Johnston J, Weiss RV, Qualy RL, et al. Hospitalized cancer patients with severe sepsis: analysis of incidence, mortality, and associated costs of care. Crit Care. 2004;8(5):R291-8.\u003c/li\u003e\n\u003cli\u003eXu G, Liu B, Sun Y, Du Y, Snetselaar LG, Hu FB, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: population based study. BMJ. 2018;362:k1497.\u003c/li\u003e\n\u003cli\u003eGeerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM). FEMS Immunol Med Microbiol. 1999;26(3-4):259-65.\u003c/li\u003e\n\u003cli\u003eCarey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study. Diabetes Care. 2018;41(3):513-21.\u003c/li\u003e\n\u003cli\u003eFahey TJ, Sadaty A, Jones WG, Barber A, Smoller B, Shires GT. Diabetes impairs the late inflammatory response to wound healing. J Surg Res. 1991;50(4):308-13.\u003c/li\u003e\n\u003cli\u003eGrossmann V, Schmitt VH, Zeller T, Panova-Noeva M, Schulz A, Laubert-Reh D, et al. Profile of the Immune and Inflammatory Response in Individuals With Prediabetes and Type 2 Diabetes. Diabetes Care. 2015;38(7):1356-64.\u003c/li\u003e\n\u003cli\u003eEstrada CA, Young JA, Nifong LW, Chitwood WR. Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting. Ann Thorac Surg. 2003;75(5):1392-9.\u003c/li\u003e\n\u003cli\u003eRohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial. Diabetes Care. 2002;25(2):275-8.\u003c/li\u003e\n\u003cli\u003eNathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia. 2007;50(11):2239-44.\u003c/li\u003e\n\u003cli\u003ePanzer S, Kronik G, Lechner K, Bettelheim P, Neumann E, Dudczak R. 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Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey. Diabetes Care. 2002;25(8):1326-30.\u003c/li\u003e\n\u003cli\u003eHerman WH, Ma Y, Uwaifo G, Haffner S, Kahn SE, Horton ES, et al. Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care. 2007;30(10):2453-7.\u003c/li\u003e\n\u003cli\u003eKaneto H. Pancreatic \u0026beta;-cell glucose toxicity in type 2 diabetes mellitus. Curr Diabetes Rev. 2015;11(1):2-6.\u003c/li\u003e\n\u003cli\u003eRobertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003;52(3):581-7.\u003c/li\u003e\n\u003cli\u003eHall E, Dekker Nitert M, Volkov P, Malmgren S, Mulder H, Bacos K, et al. The effects of high glucose exposure on global gene expression and DNA methylation in human pancreatic islets. Mol Cell Endocrinol. 2018;472:57-67.\u003c/li\u003e\n\u003cli\u003eLuethi N, Cioccari L, Tanaka A, Kar P, Giersch E, Deane AM, et al. Glycated Hemoglobin A1c Levels Are Not Affected by Critical Illness. Crit Care Med. 2016;44(9):1692-4.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"sepsis, diabetes, HbA1c, white blood cell, risk prediction","lastPublishedDoi":"10.21203/rs.3.rs-127448/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-127448/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Diabetes mellitus is a major risk factor of sepsis. The potential role of hemoglobin A1c (HbA1c) in diabetic, septic patients has not yet been studied. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e In our retrospective study we included diabetic, septic patients - in whom the diagnosis of sepsis was based on the Systemic Inflammatory Response Syndrome (SIRS) criteria (112 patients, SIRS group) - who had HbA1c levels measured either in the previous 30 days (SIRS 30d subgroup – 39 patients) or within 24 hours after their Emergency Department admission (SIRS 24h subgroup – 73 patients). We later selected those patients from the SIRS group, whose Sequential Organ Failure Assessment\u0026nbsp;(SOFA) score was ≥ 2 (55 patients, SOFA group) and these patients were also divided based on the time of HbA1c measurement (SOFA 30d subgroup – 21 patients and SOFA 24h subgroup – 34 patients). We analyzed the relationship between laboratory parameters, length of hospital stay and HbA1c. We found a significant positive correlation between glucose and HbA1c, significant negative correlations between white blood cell count (WBC) and glucose, WBC and HbA1c levels in the SIRS 24h and SOFA 24h subgroups. Furthermore there was a significant positive correlation between length of hospital stay and HbA1c in the SOFA 24h subgroup. No significant correlations were found in the SIRS 30d and SOFA 30d subgroups. \u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Based on our results normal WBC with elevated HbA1c might be considered a positive SIRS criterium in diabetic, SIRS 24h patients. Besides this potential diagnostic role, HbA1c might also be an additional prognostic biomarker in diabetic, SOFA 24h patients.\u003c/p\u003e","manuscriptTitle":"The Potential Diagnostic and Predictive Role of HbA1c in Diabetic, Septic Patients - a Retrospective Single Center Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-12-16 16:51:56","doi":"10.21203/rs.3.rs-127448/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5a3449f0-8fb5-466d-ac5d-fd2337f0499c","owner":[],"postedDate":"December 16th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":1497208,"name":"Critical Care \u0026 Emergency Medicine"}],"tags":[],"updatedAt":"2022-03-28T20:02:45+00:00","versionOfRecord":{"articleIdentity":"rs-127448","link":"https://doi.org/10.1155/2022/8543232","journal":{"identity":"emergency-medicine-international","isVorOnly":true,"title":"Emergency Medicine International"},"publishedOn":"2022-03-18 20:02:45","publishedOnDateReadable":"March 18th, 2022"},"versionCreatedAt":"2020-12-16 16:51:56","video":"","vorDoi":"10.1155/2022/8543232","vorDoiUrl":"https://doi.org/10.1155/2022/8543232","workflowStages":[]},"version":"v1","identity":"rs-127448","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-127448","identity":"rs-127448","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}