Mortality Among Hospitalized Patients With Hypoglycemia: Insulin Related and Noninsulin Related

Context: Hypoglycemia is common among hospitalized patients with and without diabetes mellitus. Objective: Investigate the association between spontaneous or insulin-related hypoglycemia and mortality in hospitalized patients. Design: Hypoglycemia was defined as blood glucose <70 mg/dl (3.9 mmol/l), including moderate (40 to 70 mg/dl, 2.2 to 3.9 mmol/l) and severe hypoglycemia (<40 mg/dl, 2.2 mmol/l). Use of insulin during hospitalization defined insulin-related hypoglycemia, thus patients were classified into 6 groups: non-insulin treated (NITC) and insulin-treated controls (ITC), insulin-related hypoglycemia (IH) or severe hypoglycemia (ISH), and non insulin-related hypoglycemia (NIH) and severe hypoglycemia (NISH). Setting and Patients: Historical prospectively data of patients ≥ 18 years of age, hospitalized in medical wards for any cause between January 2011 and December 2013. Main Outcome Measure: All-cause mortality at the end of follow-up. Results: The cohort included 33,675 patients, including 2605 with moderate hypoglycemia (IH, 1011; NIH, 1594) and 342 with severe hypoglycemia (ISH, 201; NISH,141). Overall end-of-follow-up mortality was 31.9% (NITC, 28.0%; ITC, 42.9%; NIH, 50.7%; IH, 55.3%; NISH, 70.9%; ISH, 69.1%). Compared with NITC, unadjusted hazard ratios (95% confidence intervals) for mortality were as follows: ITC, 1.7 (1.6 to 1.8), NIH, 2.2 (2.0 to 2.4), IH, 2.5 (2.2 to 2.7), NISH, 4.2 (3.5 to 5.2), and ISH, 3.8 (3.2 to 4.5); with P < 0.001. Following multivariate analysis, respective hazard ratios were 1.8, 2.1, 2.4, 3.2, and 3.6 (P < 0.001). Cause of admission did not affect the association. Conclusions: In hospitalized patients, hypoglycemia, either with insulin use or spontaneous, is associated with increased short- and long-term mortality.

[1]  H. Krumholz,et al.  Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. , 2009, JAMA.

[2]  G. Umpierrez,et al.  Risk Factors for Inpatient Hypoglycemia during Subcutaneous Insulin Therapy in Non-Critically Ill Patients with Type 2 Diabetes , 2012, Journal of diabetes science and technology.

[3]  Bernard Friedman,et al.  Multiple hospitalizations for patients with diabetes. , 2003, Diabetes care.

[4]  David V. Power,et al.  Standards of Medical Care in Diabetes: Response to position statement of the American Diabetes Association , 2006 .

[5]  C. Mariash,et al.  Temporal occurrences and recurrence patterns of hypoglycemia during hospitalization. , 2015, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[6]  Hypoglycemia in hospitalized patients. , 1987, The New England journal of medicine.

[7]  Mark Woodward,et al.  Severe hypoglycemia and risks of vascular events and death. , 2010, The New England journal of medicine.

[8]  B. Nathanson,et al.  Economic and clinical impact of inpatient diabetic hypoglycemia. , 2009, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[9]  Limin Peng,et al.  Randomized Study of Basal-Bolus Insulin Therapy in the Inpatient Management of Patients With Type 2 Diabetes Undergoing General Surgery (RABBIT 2 Surgery) , 2011, Diabetes Care.

[10]  Deborah J. Cook,et al.  Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data , 2009, Canadian Medical Association Journal.

[11]  Michael E. Matheny,et al.  Hypoglycemia and Clinical Outcomes in Patients With Diabetes Hospitalized in the General Ward , 2009, Diabetes Care.

[12]  D. Williamson,et al.  Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence , 2010, Population health metrics.

[13]  E. de Jonge,et al.  Evaluation of short-term consequences of hypoglycemia in an intensive care unit* , 2006, Critical care medicine.

[14]  Michael E. Miller,et al.  The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study , 2010, BMJ : British Medical Journal.

[15]  A. Turchin,et al.  Hypoglycemia, With or Without Insulin Therapy, Is Associated With Increased Mortality Among Hospitalized Patients , 2013, Diabetes Care.

[16]  C. Mélot,et al.  Mild hypoglycemia is strongly associated with increased intensive care unit length of stay , 2011, Annals of intensive care.

[17]  I. Shimon,et al.  Mortality risk in admitted patients with diabetes mellitus according to treatment. , 2016, Journal of diabetes and its complications.

[18]  B. Frier,et al.  Vascular disease and diabetes: is hypoglycaemia an aggravating factor? , 2008, Diabetes/metabolism research and reviews.

[19]  S. Golden,et al.  Hypoglycemia in Non-Critically Ill, Hospitalized Patients With Diabetes: Evaluation, Prevention, and Management , 2013, Hospital practice.

[20]  H. Lohmann,et al.  Hypoglycemia Aggravates Critical Illness–Induced Neurocognitive Dysfunction , 2009, Diabetes Care.

[21]  J. Zonszein,et al.  Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities. , 2011, The American journal of medicine.

[22]  Hypoglycemia as a predictor of mortality in hospitalized elderly patients. , 2003 .

[23]  N. Khardori.  Intensive Insulin Therapy and Pentastarch Resuscitation in Severe Sepsis , 2008 .

[24]  J. Krinsley,et al.  Severe hypoglycemia in critically ill patients: Risk factors and outcomes* , 2007, Critical care medicine.

[25]  Aesha Drozdowski,et al.  Standards of medical care in diabetes. , 2004, Diabetes care.

[26]  C. Cook,et al.  Characterizing glucose changes antecedent to hypoglycemic events in the intensive care unit. , 2012, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[27]  Anthony Delaney,et al.  Benefits and Risks of Tight Glucose Control in Critically Ill Adults: A Metaanalysis , 2009 .

[28]  M. Ezzati,et al.  National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants , 2011, The Lancet.

[29]  J. Newman,et al.  Hypoglycemia in hospitalized patients. Causes and outcomes. , 1986, The New England journal of medicine.

[30]  A. Naidech,et al.  Moderate Hypoglycemia is Associated With Vasospasm, Cerebral Infarction, and 3-Month Disability After Subarachnoid Hemorrhage , 2010, Neurocritical care.