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Division of Endocrinology and Metabolism, University of Tennessee Health Science Center (G.E.U., A.E.K.), Memphis, Tennessee 38163; Department of Medicine, Atlanta Medical Center (S.D.I., N.B., X.Y.), Atlanta, Georgia; and Department of Medicine, Emory University School of Medicine (L.M.T.), Atlanta, Georgia
Address all correspondence and requests for reprints to: Guillermo E. Umpierrez, M.D., University of Tennessee Health Science Center, 951 Court Avenue, Room 335M, Memphis, Tennessee 38163. E-mail: . gumpierrez{at}utmem.edu
Abstract
Admission hyperglycemia has been associated with increased hospital mortality in critically ill patients; however, it is not known whether hyperglycemia in patients admitted to general hospital wards is associated with poor outcome. The aim of this study was to determine the prevalence of in-hospital hyperglycemia and determine the survival and functional outcome of patients with hyperglycemia with and without a history of diabetes. We reviewed the medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998. New hyperglycemia was defined as an admission or in-hospital fasting glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Hyperglycemia was present in 38% of patients admitted to the hospital, of whom 26% had a known history of diabetes, and 12% had no history of diabetes before the admission. Newly discovered hyperglycemia was associated with higher in-hospital mortality rate (16%) compared with those patients with a prior history of diabetes (3%) and subjects with normoglycemia (1.7%; both P < 0.01). In addition, new hyperglycemic patients had a longer length of hospital stay, a higher admission rate to an intensive care unit, and were less likely to be discharged to home, frequently requiring transfer to a transitional care unit or nursing home facility.
Our results indicate that in-hospital hyperglycemia is a common finding and represents an important marker of poor clinical outcome and mortality in patients with and without a history of diabetes. Patients with newly diagnosed hyperglycemia had a significantly higher mortality rate and a lower functional outcome than patients with a known history of diabetes or normoglycemia.
A RELATIONSHIP between admission plasma glucose concentration and in-hospital mortality in patients with acute myocardial infarction and acute stroke has been established (1, 2, 3, 4, 5, 6). An increased risk of congestive heart failure and increased mortality rate are seen both during the acute phase and long-term follow-up of diabetic patients with myocardial infarction (4, 7). Similarly, several studies have indicated that patients with diabetes are more likely to die or to have substantial neurological disability after acute stroke than nondiabetic subjects (6, 8, 9, 10, 11, 12, 13). There is dispute, however, about whether a raised blood glucose concentration is independently associated with a poor prognosis (11, 14, 15) or may indicate a more severe illness with an increased response to stress (8, 13, 16, 17, 18). Furthermore, it is not known whether hyperglycemia in patients without critical illness admitted to general hospital wards is associated with poor outcome. If stress hyperglycemia is proven to be an independent predictor of poor outcome, a policy for early detection and glucose control may be warranted.
The aim of this study was to determine the prevalence of diabetes and hyperglycemia in hospitalized patients at a community hospital and to determine the effects of newly diagnosed hyperglycemia on survival and functional outcome after adjusting for known prognostic factors.
Materials and Methods
The medical records of 2030 consecutive adult patients admitted to Georgia Baptist Medical Center, a community teaching hospital in downtown Atlanta, GA, from July 1, 1998, to October 20, 1998, were reviewed. Of the 2030 admitted patients, 144 patients (7%) were excluded because no blood glucose measurement was recorded during the hospital stay. The remaining patients who had 1 or more glucose measurements made were divided into 3 study groups. A normoglycemic group included those patients with normal plasma glucose and no previous history of diabetes. Patients with hyperglycemia were subdivided between those with a previous history of diabetes (known diabetics) and those without a previous history of diabetes (new hyperglycemia). Hyperglycemia was defined as an admission or in-hospital fasting blood glucose level of 126 mg/dl (7 mmol/liter) or more or a random blood glucose level of 200 mg/dl (11.1 mmol/liter) or more on 2 or more determinations. Fasting blood glucose were those samples drawn from patients kept NPO or samples drawn between 04000600 h. Information regarding types of iv fluid was not recorded in this study; thus, it is possible that some patients may have received dextrose solutions at the time of hyperglycemia. Patient information was collected regarding demographic characteristics, blood glucose levels on admission and during hospital stay, concurrent medical diagnoses, medical treatment, and hospital outcome, including mortality and disposition at discharge.
The primary end point of the study was in-hospital mortality. Secondary end points included treatment of hyperglycemia, length of hospital stay, and patient disposition at discharge (discharge to personal home, transitional care or rehabilitation unit, and nursing home facility). In addition to blood glucose levels, prognostic variables considered were age, gender, body mass index, admission blood pressure, smoking status, coronary heart disease or renal failure, presence of infection, and the need for intensive care unit (ICU) admission.
Statistical analysis
To compare baseline demographics and clinical characteristics between groups, ANOVA with Scheffés method was used for continuous variables, with log transformations when necessary. For categorical variables,
2 analysis was used, with a Bonferonni correction when applicable. Multiple logistic regression and adjusted odds ratios were employed to determine the influence of demographic and clinical characteristics on mortality rates and length of stay. P < 0.05 was considered significant. StatView version 5.0 (SAS Institute, Inc., Cary, NC) was the statistical software used for the analysis.
Results
Of the 1886 study patients, 1168 (62%) had 1 or more blood glucose measurements within normal limits. The known diabetes group consisted of 495 patients (26%) with a history of diabetes mellitus documented before admission. The newly diagnosed hyperglycemia group consisted of 223 (12%) patients with no prior history of diabetes who were found to have an admission or in-hospital fasting glucose level greater than 126 mg/dl (7 mmol/liter) or a random blood glucose level greater than 200 mg/dl (11.1 mmol/liter) on 2 or more determinations.
The clinical characteristics of the three study groups are shown in Table 1
. There were no differences in the mean age, gender distribution, racial distribution, or admission blood pressure among the three groups. Patients with known diabetes tended to have a higher age and body mass index; however, these differences were not statistically significant. As expected, patients with known diabetes had significantly higher fasting and random blood glucose levels compared with the normoglycemia group (P < 0.01). The admission blood glucose level in patients with known diabetes (12.8 ± 1 mmol/liter) was higher than that in the new hyperglycemia group (10.5 ± 1 mmol/liter), but results were not statistically significant. We observed no differences among the three groups in the proportion of patients who were admitted to a medicine service vs. a surgical service.
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Newly diagnosed hyperglycemia was frequently left untreated. During the hospital course, only 13% had orders for a diabetic diet, 2% were prescribed oral hypoglycemic agents, 6% received scheduled dose insulin, and 35% received sliding scale insulin. These treatment modalities were significantly lower than those in patients with a history of diabetes, in whom 53% had orders for a diabetic diet, 33% were prescribed oral hypoglycemic agents, 32% received scheduled dose insulin, and 77% received insulin therapy.
Discussion
We found that hyperglycemia was present in 38% of patients admitted to the hospital, and that one third of these patients had no history of diabetes before the admission. Patients with new hyperglycemia had significantly higher in-hospital mortality rate and worse functional outcome than patients with a prior history of diabetes and subjects with normoglycemia. In addition, patients with new hyperglycemia had an increased length of hospital stay, were more likely to require admission to an ICU, and were more likely to require transfer to a transitional care unit or nursing home facility at discharge.
Admission hyperglycemia has been associated with increased morbidity and mortality in patients with acute critical illnesses, such as myocardial infarction and stroke (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12). In patients with acute myocardial infarction, hyperglycemia has been associated with increased risk of mortality, congestive heart failure, and cardiogenic shock in patients with and without diabetes (1, 3, 6, 20, 21, 22). Similarly, hyperglycemia in the acute phase of stroke has been suggested as a predictor of worse prognosis, in terms of both mortality and residual disability (6, 17, 18, 19, 23, 24). This study confirms these observations, but in addition it indicates that hyperglycemia is an important marker of poor clinical outcome and mortality not only in critical patients admitted to the ICU, but also in patients admitted to general medicine and surgery wards. Using multivariate odds ratios for mortality adjusted for age, body mass index, gender, hypertension, coronary artery disease, presence of infection, renal failure, and ICU admission, we found that patients with new hyperglycemia had an 18.3-fold increase in mortality rate compared with a 2.7-fold increase in the known diabetes group.
A number of features suggests that patients with newly diagnosed hyperglycemia were more severely ill than patients with known diabetes or without hyperglycemia. Patients with newly diagnosed hyperglycemia were more likely to be admitted to the ICU, had a longer length of hospital stay, and were less likely to be discharged home. More strikingly, 16% died compared with 3% of patients with a known history of diabetes and 1.7% of the normoglycemic group. An additional finding that suggests that new hyperglycemia represents a marker of a more severe illness and is not the primary cause of the increased morbidity and mortality is that the admission and random blood glucose concentrations in patients with new hyperglycemia were lower than those in patients with known diabetes. Stress hyperglycemia, defined as a transient increase in blood glucose concentration during acute physiological illness, represents two distinct populations: those with undiagnosed diabetes or impaired glucose tolerance, and those who develop hyperglycemia as the result of the severe stress and increased counterregulatory hormones. Although the underlying mechanisms for the development of stress hyperglycemia are not fully understood, several potential mechanisms have been proposed. These include increased substrate availability in the form of lactate (16, 25, 26), increased gluconeogenesis and decreased glycogenolysis due to increased secretion of counterregulatory hormones (catecholamines, cortisol, and glucagon) (12, 27, 28), and peripheral insulin resistance (29, 30). Although in such patients, the high morbidity and mortality relate to the associated illness precipitating the stress, hyperglycemia itself may contribute to morbidity by creating a toxic cellular milieu (31, 32, 33), causing intracellular and extracellular dehydration (34), inducing electrolyte abnormalities, and depressing immune function (35).
Our study did not address the question of whether treatment of hyperglycemia may reduce the high morbidity and mortality associated with hyperglycemia in patients with and without a history of diabetes. Recently, Van den Berghe et al. (36) reported that among mechanical ventilated adult patients admitted to an ICU, strict normalization of blood glucose levels (4.56.1 mmol/liter) with continuous infusion of insulin compared with a restrictive insulin regimen to maintain blood glucose levels between 1012 mmol/liter resulted in reduced hospital morbidity and mortality. The intensive insulin schedule significantly reduced ICU mortality by 43% (death odds ratio, 0.52; range, 0.330.81), hospital mortality by 34%, mean ICU stay by 22%, and incidence of bacteremia and hemodialysis by 50%. These results suggest that strict glucose control in hospitalized patients with hyperglycemia is warranted.
One limitation of our study is that we were not able to determine the percentage of patients with latent or unrecognized diabetes because of the lack of hemoglobin A1C testing and the lack of follow-up after discharge. In agreement with a previous report (37), we found that 12% or one third of all hyperglycemic patients on both medical and surgical services had no prior history of diabetes. We believe that newly diagnosed hyperglycemia is usually considered a transient finding in response to the acute illness not requiring medical intervention, as indicated by the fact that more than two thirds of these patients did not receive diabetic diet or antidiabetic drug therapy. However, given the average delay of a decade between the onset and the diagnosis of diabetes (37, 38), further evaluation of new hyperglycemic patients with in-patient determination of hemoglobin A1C may allow earlier diagnosis and treatment, which may prevent the development of chronic complications of diabetes.
In conclusion, we have shown that in-hospital hyperglycemia is a common finding and should be considered an important marker of poor clinical outcome and increased mortality, in particular in patients without a history of diabetes. Patients with new hyperglycemia admitted to critical care areas or to general medical and surgical wards had a significantly higher mortality rate and lower functional outcome than patients with a known history of diabetes or normoglycemia. Our observations indicate that all hospitalized patients should be screened for hyperglycemia.
Acknowledgments
Footnotes
Abbreviation: ICU, Intensive care unit.
Received September 10, 2001.
Accepted November 13, 2001.
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N. W. Cheung, B. Napier, C. Zaccaria, and J. P. Fletcher Hyperglycemia Is Associated With Adverse Outcomes in Patients Receiving Total Parenteral Nutrition Diabetes Care, October 1, 2005; 28(10): 2367 - 2371. [Abstract] [Full Text] [PDF] |
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D. K. Bland, Y. Fankhanel, E. Langford, M. Lee, S. W. Lee, C. Maloney, M. Rogers, and G. Zimmerman Intensive Versus Modified Conventional Control of Blood Glucose Level in Medical Intensive Care Patients: A Pilot Study Am. J. Crit. Care., September 1, 2005; 14(5): 370 - 376. [Abstract] [Full Text] [PDF] |
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R.E. Anderson, K. Klerdal, T. Ivert, N. Hammar, G. Barr, and A. Owall Are even impaired fasting blood glucose levels preoperatively associated with increased mortality after CABG surgery? Eur. Heart J., August 1, 2005; 26(15): 1513 - 1518. [Abstract] [Full Text] [PDF] |
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B. Capaldo, M. Galderisi, A. A. Turco, A. D'Errico, S. Turco, A. A. Rivellese, G. de Simone, O. de Divitiis, and G. Riccardi Acute Hyperglycemia Does Not Affect the Reactivity of Coronary Microcirculation in Humans J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3871 - 3876. [Abstract] [Full Text] [PDF] |
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A. L Blommel and R. A Lutes Severe Hyperglycemia During Renally Adjusted Gatifloxacin Therapy Ann. Pharmacother., July 1, 2005; 39(7): 1349 - 1352. [Abstract] [Full Text] [PDF] |
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D. Baldwin, G. Villanueva, R. McNutt, and S. Bhatnagar Eliminating Inpatient Sliding-Scale Insulin: A reeducation project with medical house staff Diabetes Care, May 1, 2005; 28(5): 1008 - 1011. [Abstract] [Full Text] [PDF] |
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F. A. McAlister, S. R. Majumdar, S. Blitz, B. H. Rowe, J. Romney, and T. J. Marrie The Relation Between Hyperglycemia and Outcomes in 2,471 Patients Admitted to the Hospital With Community-Acquired Pneumonia Diabetes Care, April 1, 2005; 28(4): 810 - 815. [Abstract] [Full Text] [PDF] |
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S. E. Inzucchi and J. Rosenstock Counterpoint: Inpatient Glucose Management: A premature call to arms? Diabetes Care, April 1, 2005; 28(4): 976 - 979. [Full Text] [PDF] |
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T. M Conner, K. R Flesner-Gurley, and J. C Barner Hyperglycemia in the Hospital Setting: The Case for Improved Control Among Non-Diabetics Ann. Pharmacother., March 1, 2005; 39(3): 492 - 501. [Abstract] [Full Text] [PDF] |
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C. L. Thompson, K. C. Dunn, M. C. Menon, L. E. Kearns, and S. S. Braithwaite Hyperglycemia in the Hospital Diabetes Spectr, January 1, 2005; 18(1): 20 - 27. [Abstract] [Full Text] [PDF] |
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P. A. Goldberg and S. E. Inzucchi Selling Root Canals: Lessons Learned From Implementing a Hospital Insulin Infusion Protocol Diabetes Spectr, January 1, 2005; 18(1): 28 - 33. [Abstract] [Full Text] [PDF] |
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A. T. Nettles Patient Education in the Hospital Diabetes Spectr, January 1, 2005; 18(1): 44 - 48. [Abstract] [Full Text] [PDF] |
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J. Najarian, D. Swavely, E. Wilson, L. Merkle, T. Wasser, A. H. Quinn, S. Urffer, and M. Young Improving Outcomes for Diabetic Patients Undergoing Vascular Surgery Diabetes Spectr, January 1, 2005; 18(1): 53 - 60. [Abstract] [Full Text] [PDF] |
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American Diabetes Association Standards of Medical Care in Diabetes Diabetes Care, January 1, 2005; 28(suppl_1): S4 - S36. [Full Text] [PDF] |
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A. G. Pittas, R. D. Siegel, and J. Lau Insulin Therapy for Critically Ill Hospitalized Patients: A Meta-analysis of Randomized Controlled Trials Arch Intern Med, October 11, 2004; 164(18): 2005 - 2011. [Abstract] [Full Text] [PDF] |
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C. M. Cely, P. Arora, A. A. Quartin, D. H. Kett, and R. M. H. Schein Relationship of Baseline Glucose Homeostasis to Hyperglycemia During Medical Critical Illness Chest, September 1, 2004; 126(3): 879 - 887. [Abstract] [Full Text] [PDF] |
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Z. T. Bloomgarden Inpatient Diabetes Control: Approaches to treatment Diabetes Care, September 1, 2004; 27(9): 2272 - 2277. [Full Text] [PDF] |
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Z. T. Bloomgarden Inpatient Diabetes Control: Rationale Diabetes Care, August 1, 2004; 27(8): 2074 - 2080. [Full Text] [PDF] |
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F. B. Stentz, G. E. Umpierrez, R. Cuervo, and A. E. Kitabchi Proinflammatory Cytokines, Markers of Cardiovascular Risks, Oxidative Stress, and Lipid Peroxidation in Patients With Hyperglycemic Crises Diabetes, August 1, 2004; 53(8): 2079 - 2086. [Abstract] [Full Text] [PDF] |
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D. B. Coursin and R. C. Prielipp The New Anesthesia Diet Plan: Keeping Perioperative Carbs in Check Anesth. Analg., August 1, 2004; 99(2): 316 - 318. [Full Text] [PDF] |
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K. B. Campbell and S. S. Braithwaite Hospital Management of Hyperglycemia Clin. Diabetes, April 1, 2004; 22(2): 81 - 88. [Full Text] [PDF] |
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E. S. Nylen and B. Muller Endocrine Changes in Critical Illness J Intensive Care Med, March 1, 2004; 19(2): 67 - 82. [Abstract] [PDF] |
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S. K. Andersen, J. Gjedsted, C. Christiansen, and E. Tonnesen The roles of insulin and hyperglycemia in sepsis pathogenesis J. Leukoc. Biol., March 1, 2004; 75(3): 413 - 421. [Abstract] [Full Text] [PDF] |
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P. A. Goldberg, M. D. Siegel, R. S. Sherwin, J. I. Halickman, M. Lee, V. A. Bailey, S. L. Lee, J. D. Dziura, and S. E. Inzucchi Implementation of a Safe and Effective Insulin Infusion Protocol in a Medical Intensive Care Unit Diabetes Care, February 1, 2004; 27(2): 461 - 467. [Abstract] [Full Text] [PDF] |
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S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch Management of Diabetes and Hyperglycemia in Hospitals Diabetes Care, February 1, 2004; 27(2): 553 - 591. [Full Text] [PDF] |
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R. Marfella, C. Di Filippo, K. Esposito, F. Nappo, E. Piegari, S. Cuzzocrea, L. Berrino, F. Rossi, D. Giugliano, and M. D'Amico Absence of Inducible Nitric Oxide Synthase Reduces Myocardial Damage During Ischemia Reperfusion in Streptozotocin-Induced Hyperglycemic Mice Diabetes, February 1, 2004; 53(2): 454 - 462. [Abstract] [Full Text] |
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Z. T. Bloomgarden Aspects of Blood Pressure, Lipid, and Glycemic Treatment Diabetes Care, January 1, 2004; 27(1): 264 - 269. [Full Text] [PDF] |
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D. B. Coursin and M. J. Murray How Sweet is Euglycemia in Critically Ill Patients? Mayo Clin. Proc., December 1, 2003; 78(12): 1460 - 1462. [PDF] |
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D.M. Bravata, N. Kim, J. Concato, and L.M. Brass Hyperglycaemia in patients with acute ischaemic stroke: how often do we screen for undiagnosed diabetes? QJM, July 1, 2003; 96(7): 491 - 497. [Abstract] [Full Text] [PDF] |
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A. Kretowski, I. Kinalska, K. Esposito, F. Nappo, R. Marfella, G. Giugliano, F. Giugliano, M. Ciotola, D. Giugliano, L. Quagliaro, et al. Serum Levels of Interleukin-18--a Potential Marker of Cardiovascular Death--Could Be Determined by Genetic Predisposition * Response Circulation, June 10, 2003; 107 (22): e206 - e207. [Full Text] [PDF] |
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B. S. Freeland, Diabetic Ketoacidosis The Diabetes Educator, May 1, 2003; 29(3): 384 - 395. [PDF] |
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K. Esposito, R. Marfella, and D. Giugliano Stress Hyperglycemia, Inflammation, and Cardiovascular Events Diabetes Care, May 1, 2003; 26(5): 1650 - 1651. [Full Text] [PDF] |
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B. Philips and E. Baker Editorial III: Hyperglycaemia and the lung Br. J. Anaesth., April 1, 2003; 90(4): 430 - 433. [Full Text] [PDF] |
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L. S. Greci, M. Kailasam, S. Malkani, D. L. Katz, I. Hulinsky, R. Ahmadi, and H. Nawaz Utility of HbA1c Levels for Diabetes Case Finding in Hospitalized Patients With Hyperglycemia Diabetes Care, April 1, 2003; 26(4): 1064 - 1068. [Abstract] [Full Text] [PDF] |
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M. Cakir, H. Altunbas, and U. Karayalcin Hyperglycemia: An Independent Marker of In-Hospital Mortality in Patients with Undiagnosed Diabetes J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1402 - 1402. [Full Text] [PDF] |
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P. Dandona, A. Aljada, and A. Bandyopadhyay The Potential Therapeutic Role of Insulin in Acute Myocardial Infarction in Patients Admitted to Intensive Care and in Those With Unspecified Hyperglycemia Diabetes Care, February 1, 2003; 26(2): 516 - 519. [Full Text] [PDF] |
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V. M. Montori, B. R. Bistrian, and M. M. McMahon Hyperglycemia in Acutely Ill Patients JAMA, November 6, 2002; 288(17): 2167 - 2169. [Full Text] [PDF] |
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I. B. Hirsch In-Patient Hyperglycemia--Are We Ready to Treat It Yet? J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 975 - 977. [Full Text] [PDF] |
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