Abstract
Hypoglycemia in the inpatient setting is a common occurrence with potentially harmful outcomes. Large trials in both the inpatient and outpatient settings have found a correlation between hypoglycemia and morbidity and mortality. The incidence of hypoglycemia is difficult to assess, due to a lack of standardized definitions and different methods of data collection between hospital systems. Risk factors that predispose to hypoglycemia involve the changing clinical statuses of patients, nutrition issues, and hospital processes. Mechanisms contributing to morbidity due to hypoglycemia may include an increase in sympathoadrenal responses, as well as indirect changes affecting cytokine production, coagulation, fibrinolysis, and endothelial function. Prevention of hypoglycemia requires implementation of several strategies that include patient safety, quality control, multidisciplinary communication, and transitions of care. In this article, we discuss all of these issues and provide suggestions to help predict and prevent hypoglycemic episodes during an inpatient stay. We address the issues that occur upon admission, during the hospital stay, and around the time of discharge. We believe that decreasing the incidence of inpatient hypoglycemia will both decrease costs and improve patient outcomes.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Umpierrez GE, Hor T, Smiley D, Temponi A, Umpierrez D, Ceron M, et al. Comparison of inpatient insulin regimens with detemir plus aspart versus neutral protamine hagedorn plus regular in medical patients with type 2 diabetes. J Clin Endocrinol Metab. 2009;94:564–9. doi:10.1210/jc.2008-1441.
Turchin A, Matheny ME, Shubina M, Scanlon JV, Greenwood B, Pendergrass ML. Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care. 2009;32:1153–7. doi:10.2337/dc08-2127.
Elliott MB, Schafers SJ, McGill JB, Tobin GS. Prediction and prevention of treatment-related inpatient hypoglycemia. J Diabetes Sci Technol. 2012;6:302–9.
ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, Neal B, Billot L, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72. doi:10.1056/NEJMoa0802987.
•• NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360:1283–97. doi:10.1056/NEJMoa0810625. This is an important trial that provided evidence that inpatient hypoglycemia may be detrimental.
Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358:125–39. doi:10.1056/NEJMoa070716.
Preiser JC, Devos P, Ruiz-Santana S, Melot C, Annane D, Groeneveld J, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Intensive Care Med. 2009;35:1738–48. doi:10.1007/s00134-009-1585-2.
• Umpierrez GE, Smiley D, Jacobs S, Peng L, Temponi A, Mulligan P, 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). Diabetes Care. 2011;34:256–61. doi:10.2337/dc10-1407. This study shows the methods by which inpatients can be treated without undue hypoglycemia.
Varghese P, Gleason V, Sorokin R, Senholzi C, Jabbour S, Gottlieb JE. Hypoglycemia in hospitalized patients treated with antihyperglycemic agents. J Hosp Med. 2007;2:234–40. doi:10.1002/jhm.212.
Cook CB, Kongable GL, Potter DJ, Abad VJ, Leija DE, Anderson M. Inpatient glucose control: a glycemic survey of 126 U.S. hospitals. J Hosp Med. 2009;4:E7–E14. doi:10.1002/jhm.533.
Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, Goff Jr DC, Bigger JT, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59. doi:10.1056/NEJMoa0802743.
•• Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005;28:1245–9. This is a useful guideline to what is defined as hypoglycemia and why and how it can be reported.
Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 2009;15:353–69. doi:10.4158/EP09102.RA.
van der Crabben SN, Blumer RM, Stegenga ME, Ackermans MT, Endert E, Tanck MW, et al. Early endotoxemia increases peripheral and hepatic insulin sensitivity in healthy humans. J Clin Endocrinol Metab. 2009;94:463–8. doi:10.1210/jc.2008-0761.
Farrokhi F, Klindukhova O, Chandra P, Peng L, Smiley D, Newton C, et al. Risk factors for inpatient hypoglycemia during subcutaneous insulin therapy in non-critically ill patients with type 2 diabetes. J Diabetes Sci Technol. 2012;6:1022–9.
Maynard G, Wesorick DH, O'Malley C, Inzucchi SE, Society of Hospital Medicine Glycemic Control Task Force. Subcutaneous insulin order sets and protocols: effective design and implementation strategies. J Hosp Med. 2008;3:29–41. doi:10.1002/jhm.354.
Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129–39. doi:10.1056/NEJMoa0808431.
• Desouza CV, Bolli GB, Fonseca V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care. 2010;33:1389–94. doi:10.2337/dc09-2082. Useful review of the CVD risk that might be associated with severe hypoglycemia and the mechanisms involved.
Smith WD, Winterstein AG, Johns T, Rosenberg E, Sauer BC. Causes of hyperglycemia and hypoglycemia in adult inpatients. Am J Health Syst Pharm. 2005;62:714–9.
Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:16–38. doi:10.1210/jc.2011-2098.
Hellman R. A systems approach to reducing errors in insulin therapy in the inpatient setting. Endocr Pract. 2004;10 Suppl 2:100–8.
Hellman R. Patient safety and inpatient glycemic control: translating concepts into action. Endocr Pract. 2006;12 Suppl 3:49–55.
Umpierrez GE, Palacio A, Smiley D. Sliding scale insulin use: myth or insanity? Am J Med. 2007;120:563–7. doi:10.1016/j.amjmed.2006.05.070.
Goldberg PA, Siegel MD, Sherwin RS, Halickman JI, Lee M, Bailey VA, et al. Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care. 2004;27:461–7.
Donihi AC, Raval D, Saul M, Korytkowski MT, DeVita MA. Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients. Endocr Pract. 2006;12:358–62.
Noschese M, Donihi AC, Koerbel G, Karslioglu E, Dinardo M, Curll M, et al. Effect of a diabetes order set on glycaemic management and control in the hospital. Qual Saf Health Care. 2008;17:464–8. doi:10.1136/qshc.2006.021790.
Cohen MR, Proulx SM, Crawford SY. Survey of hospital systems and common serious medication errors. J Healthc Risk Manag. 1998;18:16–27. doi:10.1002/jhrm.5600180104.
Amori RE, Pittas AG, Siegel RD, Kumar S, Chen JS, Karnam S, et al. Inpatient medical errors involving glucose-lowering medications and their impact on patients: review of 2,598 incidents from a voluntary electronic error-reporting database. Endocr Pract. 2008;14:535–42.
Kosiborod M, Inzucchi SE, Goyal A, Krumholz HM, Masoudi FA, Xiao L, et al. Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA. 2009;301:1556–64. doi:10.1001/jama.2009.496.
Boucai L, Southern WN, Zonszein J. Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities. Am J Med. 2011;124:1028–35. doi:10.1016/j.amjmed.2011.07.011.
van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001;345:1359–67. doi:10.1056/NEJMoa011300.
Schwartz NS, Clutter WE, Shah SD, Cryer PE. Glycemic thresholds for activation of glucose counterregulatory systems are higher than the threshold for symptoms. J Clin Invest. 1987;79:777–81. doi:10.1172/JCI112884.
Mitrakou A, Ryan C, Veneman T, Mokan M, Jenssen T, Kiss I, et al. Hierarchy of glycemic thresholds for counterregulatory hormone secretion, symptoms, and cerebral dysfunction. Am J Physiol. 1991;260:E67–74.
Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Ciofetta M, Modarelli F, et al. Relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycaemia in male and female humans. Diabetologia. 1994;37:797–807.
Hilsted J, Bonde-Petersen F, Norgaard MB, Greniman M, Christensen NJ, Parving HH, et al. Haemodynamic changes in insulin-induced hypoglycaemia in normal man. Diabetologia. 1984;26:328–32.
Egeli ES, Berkmen R. Action of hypoglycemia on coronary insufficiency and mechanism of ECG alterations. Am Heart J. 1960;59:527–40.
Galloway PJ, Thomson GA, Fisher BM, Semple CG. Insulin-induced hypoglycemia induces a rise in C-reactive protein. Diabetes Care. 2000;23:861–2.
Razavi Nematollahi L, Kitabchi AE, Stentz FB, Wan JY, Larijani BA, Tehrani MM, et al. Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. Metabolism. 2009;58:443–8. doi:10.1016/j.metabol.2008.10.018.
Del Rey A, Roggero E, Randolf A, Mahuad C, McCann S, Rettori V, et al. IL-1 resets glucose homeostasis at central levels. Proc Natl Acad Sci U S A. 2006;103:16039–44. doi:10.1073/pnas.0607076103.
Fisher BM, Hepburn DA, Smith JG, Frier BM. Responses of peripheral blood cells to acute insulin-induced hypoglycaemia in humans: effect of alpha-adrenergic blockade. Horm Metab Res Suppl. 1992;26:109–10.
Gill GV, Woodward A, Casson IF, Weston PJ. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes–the ‘dead in bed’ syndrome revisited. Diabetologia. 2009;52:42–5. doi:10.1007/s00125-008-1177-7.
Laitinen T, Lyyra-Laitinen T, Huopio H, Vauhkonen I, Halonen T, Hartikainen J, et al. Electrocardiographic alterations during hyperinsulinemic hypoglycemia in healthy subjects. Ann Noninvasive Electrocardiol. 2008;13:97–105. doi:10.1111/j.1542-474X.2008.00208.x.
Robinson RT, Harris ND, Ireland RH, Lee S, Newman C, Heller SR. Mechanisms of abnormal cardiac repolarization during insulin-induced hypoglycemia. Diabetes. 2003;52:1469–74.
Koivikko ML, Karsikas M, Salmela PI, Tapanainen JS, Ruokonen A, Seppanen T, et al. Effects of controlled hypoglycaemia on cardiac repolarisation in patients with type 1 diabetes. Diabetologia. 2008;51:426–35. doi:10.1007/s00125-007-0902-y.
Umpierrez GE, Smiley D, Zisman A, Prieto LM, Palacio A, Ceron M, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30:2181–6. doi:10.2337/dc07-0295.
Maynard G, Lee J, Phillips G, Fink E, Renvall M. Improved inpatient use of basal insulin, reduced hypoglycemia, and improved glycemic control: effect of structured subcutaneous insulin orders and an insulin management algorithm. J Hosp Med. 2009;4:3–15. doi:10.1002/jhm.391.
Korytkowski M, Dinardo M, Donihi AC, Bigi L, Devita M. Evolution of a diabetes inpatient safety committee. Endocr Pract. 2006;12 Suppl 3:91–9.
Schnipper JL, Magee M, Larsen K, Inzucchi SE, Maynard G, Society of Hospital Medicine Glycemic Control Task Force. Society of Hospital Medicine Glycemic Control Task Force summary: practical recommendations for assessing the impact of glycemic control efforts. J Hosp Med. 2008;3:66–75. doi:10.1002/jhm.356.
Bode BW, Braithwaite SS, Steed RD, Davidson PC. Intravenous insulin infusion therapy: indications, methods, and transition to subcutaneous insulin therapy. Endocr Pract. 2004;10 Suppl 2:71–80.
Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse events affecting patients after discharge from the hospital. Ann Intern Med. 2003;138:161–7.
Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med. 1997;157:1681–6.
Clement S, Braithwaite SS, Magee MF, Ahmann A, Smith EP, Schafer RG, et al. Management of diabetes and hyperglycemia in hospitals. Diabetes Care. 2004;27:553–91.
Lauster CD, Gibson JM, DiNella JV, DiNardo M, Korytkowski MT, Donihi AC. Implementation of standardized instructions for insulin at hospital discharge. J Hosp Med. 2009;4:E41–2. doi:10.1002/jhm.489.
Acknowledgments
The contents of this article do not reflect the views of the VA and are the opinion of the authors.
Compliance with Ethics Guidelines
ᅟ
Conflict of Interest
Leslie Eiland, Whitney Goldner, Andjela Drincic, and Cyrus Desouza declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is part of the Topical Collection on Hospital Management of Diabetes
Rights and permissions
About this article
Cite this article
Eiland, L., Goldner, W., Drincic, A. et al. Inpatient Hypoglycemia: A Challenge That Must Be Addressed. Curr Diab Rep 14, 445 (2014). https://doi.org/10.1007/s11892-013-0445-1
Published:
DOI: https://doi.org/10.1007/s11892-013-0445-1