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  • Review Article
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Diabetic emergencies — ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia

Key Points

  • Diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar state (HHS) are serious acute metabolic complications of diabetes mellitus, representing points along a spectrum of hyperglycaemic emergencies caused by poor glycaemic control

  • DKA comprises hyperglycaemia, hyperketonaemia and metabolic acidosis; diagnostic criteria for HHS include a plasma glucose level >33.3 mmol/l, serum osmolality >320 mmol/kg and no appreciable metabolic acidosis and ketonaemia

  • Management objectives for DKA and HHS include restoration of circulatory volume and tissue perfusion; correction of hyperglycaemia, ketogenesis and electrolyte imbalance; and identification and treatment of the precipitating event

  • Hypoglycaemia is defined as a blood glucose level <3.9 mmol/l in both the inpatient and outpatient settings

  • Severe hypoglycaemic events can negate the beneficial effects of intensive glycaemic management strategies that target near normoglycaemia among patients with diabetes mellitus

  • Patient and family education regarding the signs and symptoms of hypoglycaemia, as well as the methods available for treatment, can effectively reduce the risk of severe hypoglycaemic episodes

Abstract

Diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS) and hypoglycaemia are serious complications of diabetes mellitus that require prompt recognition, diagnosis and treatment. DKA and HHS are characterized by insulinopaenia and severe hyperglycaemia; clinically, these two conditions differ only by the degree of dehydration and the severity of metabolic acidosis. The overall mortality recorded among children and adults with DKA is <1%. Mortality among patients with HHS is 10-fold higher than that associated with DKA. The prognosis and outcome of patients with DKA or HHS are determined by the severity of dehydration, the presence of comorbidities and age >60 years. The estimated annual cost of hospital treatment for patients experiencing hyperglycaemic crises in the USA exceeds US$2 billion. Hypoglycaemia is a frequent and serious adverse effect of antidiabetic therapy that is associated with both immediate and delayed adverse clinical outcomes, as well as increased economic costs. Inpatients who develop hypoglycaemia are likely to experience a long duration of hospital stay and increased mortality. This Review describes the clinical presentation, precipitating causes, diagnosis and acute management of these diabetic emergencies, including a discussion of practical strategies for their prevention.

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Figure 1: Protocol for management of adult patients with diabetic ketoacidosis and hyperglycaemic hyperosmolar state recommended by the ADA.
Figure 2: Differential effects of daytime versus night time hypoglycaemia on cardiovascular risk.

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References

  1. Kitabchi, A. E., Umpierrez, G. E., Miles, J. M. & Fisher, J. N. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 32, 1335–1343 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Centers for Disease Control and Prevention. Diabetes data & trends. [online], (2015).

  3. Fishbein, H. A. & Palumbo, P. J. in Diabetes in America 2nd edn Ch. 13 283–291 (National Institutes of Health, 1995).

    Google Scholar 

  4. Pasquel, F. J. & Umpierrez, G. E. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care 37, 3124–3131 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Geller, A. I. et al. National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. JAMA Int. Med. 174, 678–686 (2014).

    Article  CAS  Google Scholar 

  6. Krikorian, A., Ismail-Beigi, F. & Moghissi, E. S. Comparisons of different insulin infusion protocols: a review of recent literature. Curr. Opin. Clin. Nutr. Metab. Care 13, 198–204 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Umpierrez, G. E. et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care 30, 2181–2186 (2007).

    Article  CAS  PubMed  Google Scholar 

  8. Umpierrez, E. 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 34, 256–261 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Basu, A. et al. Persisting mortality in diabetic ketoacidosis. Diabet. Med. 10, 282–284 (1993).

    Article  CAS  PubMed  Google Scholar 

  10. Malone, M. L., Gennis, V. & Goodwin, J. S. Characteristics of diabetic ketoacidosis in older versus younger adults. J. Am. Geriatr. Soc. 40, 1100–1104 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Bhowmick, S. K., Levens, K. L. & Rettig, K. R. Hyperosmolar hyperglycemic crisis: an acute life-threatening event in children and adolescents with type 2 diabetes mellitus. Endocr. Pract. 11, 23–29 (2005).

    Article  PubMed  Google Scholar 

  12. Fadini, G. P. et al. Characteristics and outcomes of the hyperglycemic hyperosmolar non-ketotic syndrome in a cohort of 51 consecutive cases at a single center. Diabetes Res. Clin. Pract. 94, 172–179 (2011).

    Article  PubMed  Google Scholar 

  13. McCoy, R. G. et al. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 35, 1897–1901 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kitabchi, A. E. et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 24, 131–153 (2001).

    Article  CAS  PubMed  Google Scholar 

  15. Umpierrez, G. E., Kelly, J. P., Navarrete, J. E., Casals, M. M. & Kitabchi, A. E. Hyperglycemic crises in urban blacks. Arch. Intern. Med. 157, 669–675 (1997).

    Article  CAS  PubMed  Google Scholar 

  16. Boucai, L., Southern, W. N. & Zonszein, J. Hypoglycemia-associated mortality is not drug-associated but linked to comorbidities. Am. J. Med. 124, 1028–1035 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Kosiborod, M. et al. Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. JAMA 301, 1556–1564 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Garg, R., Hurwitz, S., Turchin, A. & Trivedi, A. Hypoglycemia, with or without insulin therapy, is associated with increased mortality among hospitalized patients. Diabetes Care 36, 1107–1110 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Finfer, S. et al. Hypoglycemia and risk of death in critically ill patients. N. Engl. J. Med. 367, 1108–1118 (2012).

    Article  CAS  PubMed  Google Scholar 

  20. Carey, M., Boucai, L. & Zonszein, J. Impact of hypoglycemia in hospitalized patients. Curr. Diabetes Rep. 13, 107–113 (2013).

    Article  Google Scholar 

  21. Rhoads, G. G. et al. Contribution of hypoglycemia to medical care expenditures and short-term disability in employees with diabetes. J. Occup. Environ. Med. 47, 447–452 (2005).

    Article  PubMed  Google Scholar 

  22. Turchin, A. et al. Hypoglycemia and clinical outcomes in patients with diabetes hospitalized in the general ward. Diabetes Care 32, 1153–1157 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Randall, L. et al. Recurrent diabetic ketoacidosis in inner-city minority patients: behavioral, socioeconomic, and psychosocial factors. Diabetes Care 34, 1891–1896 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Taylor, S. I., Blau, J. E. & Rother, K. I. SGLT2 inhibitors may predispose to ketoacidosis. J. Clin. Endocrinol. Metab. 100, 2849–2852 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Peters, A. L. et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 38, 1687–1693 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Ennis, E. D., Stahl, E. J. & Kreisberg, R. A. The hyperosmolar hyperglycemic syndrome. Diabetes Rev. 2, 115–126 (1994).

    Google Scholar 

  27. Foster, D. W. & McGarry, J. D. The metabolic derangements and treatment of diabetic ketoacidosis. N. Engl. J. Med. 309, 159–169 (1983).

    Article  CAS  PubMed  Google Scholar 

  28. McGarry, J. D. & Foster, D. W. Regulation of hepatic fatty acid oxidation and ketone body production. Ann. Rev. Biochem. 49, 395–420 (1980).

    Article  CAS  PubMed  Google Scholar 

  29. McGarry, J. D., Woeltje, K. F., Kuwajima, M. & Foster, D. W. Regulation of ketogenesis and the renaissance of carnitine palmitoyltransferase. Diabetes Metab. Rev. 5, 271–284 (1989).

    Article  CAS  PubMed  Google Scholar 

  30. Reichard, G. A. Jr, Skutches, C. L., Hoeldtke, R. D. & Owen, O. E. Acetone metabolism in humans during diabetic ketoacidosis. Diabetes 35, 668–674 (1986).

    Article  PubMed  Google Scholar 

  31. Gerich, J. E., Martin, M. M. & Recant, L. Clinical and metabolic characteristics of hyperosmolar nonketotic coma. Diabetes 20, 228–238 (1971).

    Article  CAS  PubMed  Google Scholar 

  32. Umpierrez, G. & Freire, A. X. Abdominal pain in patients with hyperglycemic crises. J. Crit. Care 17, 63–67 (2002).

    Article  PubMed  Google Scholar 

  33. Guo, R. X., Yang, L. Z., Li, L. X. & Zhao, X. P. Diabetic ketoacidosis in pregnancy tends to occur at lower blood glucose levels: case–control study and a case report of euglycemic diabetic ketoacidosis in pregnancy. J. Obstet. Gynaecol. Res. 34, 324–330 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Stephens, J. M., Sulway, M. J. & Watkins, P. J. Relationship of blood acetoacetate and 3-hydroxybutyrate in diabetes. Diabetes 20, 485–489 (1971).

    Article  CAS  PubMed  Google Scholar 

  35. Sheikh-Ali, M. et al. Can serum β-hydroxybutyrate be used to diagnose diabetic ketoacidosis? Diabetes Care 31, 643–647 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Taboulet, P. et al. Urinary acetoacetate or capillary β-hydroxybutyrate for the diagnosis of ketoacidosis in the emergency department setting. Eur. J. Emerg. Med. 11, 251–258 (2004).

    Article  PubMed  Google Scholar 

  37. Arieff, A. I. & Kleeman, C. R. Cerebral edema in diabetic comas. II. Effects of hyperosmolality, hyperglycemia and insulin in diabetic rabbits. J. Clin. Endocrinol. Metab. 38, 1057–1067 (1974).

    Article  CAS  PubMed  Google Scholar 

  38. Luzi, L., Barrett, E. J., Groop, L. C., Ferrannini, E. & DeFronzo, R. A. Metabolic effects of low-dose insulin therapy on glucose metabolism in diabetic ketoacidosis. Diabetes 37, 1470–1477 (1988).

    Article  CAS  PubMed  Google Scholar 

  39. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Hyperglycemic emergencies in adults. Can. J. Diabetes 37, S72–S76 (2013).

  40. Goyal, N., Miller, J. B., Sankey, S. S. & Mossallam, U. Utility of initial bolus insulin in the treatment of diabetic ketoacidosis. J. Emerg. Med. 38, 422–427 (2010).

    Article  PubMed  Google Scholar 

  41. Kitabchi, A. E., Ayyagari, V. & Guerra, S. M. The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis. Ann. Intern. Med. 84, 633–638 (1976).

    Article  CAS  PubMed  Google Scholar 

  42. Umpierrez, G. E. et al. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial. Diabetes Care 32, 1164–1169 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Umpierrez, G. E. et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am. J. Med. 117, 291–296 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Ersoz, H. O. et al. Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients. Int. J. Clin. Pract. 60, 429–433 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Karoli, R., Fatima, J., Salman, T., Sandhu, S. & Shankar, R. Managing diabetic ketoacidosis in non-intensive care unit setting: role of insulin analogs. Indian J. Pharmacol. 43, 398–401 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Umpierrez, G. E. et al. Subcutanbeous aspart insulin: a safe and cost effective treatment of diabetic ketoacidosis. Diabetes 52 (Suppl. 1), 584A (2003).

    Google Scholar 

  47. Sobngwi, E. et al. Evaluation of a simple management protocol for hyperglycaemic crises using intramuscular insulin in a resource-limited setting. Diabetes Metab. 35, 404–409 (2009).

    Article  CAS  PubMed  Google Scholar 

  48. Adrogue, H. J., Lederer, E. D., Suki, W. N. & Eknoyan, G. Determinants of plasma potassium levels in diabetic ketoacidosis. Med. (Baltimore) 65, 163–172 (1986).

    Article  CAS  Google Scholar 

  49. Chua, H. R., Schneider, A. & Bellomo, R. Bicarbonate in diabetic ketoacidosis — a systematic review. Ann. Intensive Care 1, 23 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Fisher, J. N. & Kitabchi, A. E. A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J. Clin. Endocrinol. Metab. 57, 177–180 (1983).

    Article  CAS  PubMed  Google Scholar 

  51. Wilson, H. K., Keuer, S. P., Lea, A. S. & Boyd, A. E. 3rd & Eknoyan, G. Phosphate therapy in diabetic ketoacidosis. Arch. Intern. Med. 142, 517–520 (1982).

    Article  CAS  PubMed  Google Scholar 

  52. Winter, R. J., Harris, C. J., Phillips, L. S. & Green, O. C. Diabetic ketoacidosis: induction of hypocalcemia and hypomagnesemia by phosphate therapy. Am. J. Med. 67, 897–900 (1979).

    Article  CAS  PubMed  Google Scholar 

  53. White, N. H. Diabetic ketoacidosis in children. Endocrinol. Metab. Clin. North Am. 29, 657–682 (2000).

    Article  CAS  PubMed  Google Scholar 

  54. Savage, M. W. et al. Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis. Diabet. Med. 28, 508–515 (2011).

    Article  CAS  PubMed  Google Scholar 

  55. Hsia, E. et al. Subcutaneous administration of glargine to diabetic patients receiving insulin infusion prevents rebound hyperglycemia. J. Clin. Endocrinol. Metab. 97, 3132–3137 (2012).

    Article  CAS  PubMed  Google Scholar 

  56. Jefferies, C. A. et al. Preventing diabetic ketoacidosis. Pediatr. Clin. North Am. 62, 857–871 (2012).

    Article  Google Scholar 

  57. Vanelli, M. et al. Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care 22, 7–9 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Laffel, L. Sick-day management in type 1 diabetes. Endocrinol. Metab. Clin. North Am. 29, 707–723 (2000).

    Article  CAS  PubMed  Google Scholar 

  59. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood. [online], (2015).

  60. European Medicines Agency. Review of diabetes medicines called SGLT2 inhibitors started. Risk of diabetic ketoacidosis to be examined. [online], (2015).

  61. Erondu, N., Desai, M., Ways, K. & Meininger, G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 38, 1680–1686 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Cryer, P. E. Glycemic goals in diabetes: trade-off between glycemic control and iatrogenic hypoglycemia. Diabetes 63, 2188–2195 (2014).

    Article  PubMed  Google Scholar 

  63. Cryer, P. Hypoglycemia during therapy of diabetes. Endotext.org[online], (2015).

  64. Cryer, P. E. Hypoglycemia-associated autonomic failure in diabetes: maladaptive, adaptive, or both? Diabetes 64, 2322–2323 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Weinstock, R. S. et al. Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry. J. Clin. Endocrinol. Metab. 98, 3411–3419 (2013).

    Article  CAS  PubMed  Google Scholar 

  66. Miller, C. D. et al. Hypoglycemia in patients with type 2 diabetes mellitus. Arch. Intern. Med. 161, 1653–1659 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. McCoy, R. G. et al. Self-report of hypoglycemia and health-related quality of life in patients with type 1 and type 2 diabetes. Endocr. Pract. 19, 792–799 (2013).

    Article  PubMed  Google Scholar 

  68. Wexler, D. J., Meigs, J. B., Cagliero, E., Nathan, D. M. & Grant, R. W. Prevalence of hyper- and hypoglycemia among inpatients with diabetes: a national survey of 44 U.S. hospitals. Diabetes Care 30, 367–369 (2007).

    Article  PubMed  Google Scholar 

  69. Umpierrez, G. E. et al. Randomized study comparing a basal-bolus with a basal plus correction insulin regimen for the hospital management of medical and surgical patients with type 2 diabetes: basal plus trial. Diabetes Care 36, 2169–2174 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Lleva, R. R., Thomas, P., Bozzo, J. E., Hendrickson, K. C. & Inzucchi, S. E. Using the glucometrics website to benchmark ICU glucose control before and after the NICE-SUGAR study. J. Diabetes Sci. Technol. 8, 918–922 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Leese, G. P. et al. Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use. Diabetes Care 26, 1176–1180 (2003).

    Article  PubMed  Google Scholar 

  72. Kerry, C., Mitchell, S., Sharma, S., Scott, A. & Rayman, G. Diurnal temporal patterns of hypoglycaemia in hospitalized people with diabetes may reveal potentially correctable factors. Diabet. Med. 30, 1403–1406 (2013).

    Article  CAS  PubMed  Google Scholar 

  73. Seaquist, E. R. et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. J. Clin. Endocrinol. Metab. 98, 1845–1859 (2013).

    Article  CAS  PubMed  Google Scholar 

  74. Seaquist, E. R. et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 36, 1384–1395 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Cryer, P. E., Davis, S. N. & Shamoon, H. Hypoglycemia in diabetes. Diabetes Care 26, 1902–1912 (2003).

    Article  CAS  PubMed  Google Scholar 

  76. Moghissi, E. S. et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr. Pract. 15, 353–369 (2009).

    Article  PubMed  Google Scholar 

  77. Moghissi, E. S. et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care 32, 1119–1131 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Umpierrez, G. E. et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 97, 16–38 (2012).

    Article  CAS  PubMed  Google Scholar 

  79. Hsu, P. F. et al. Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care 36, 894–900 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Chow, E. et al. Risk of cardiac arrhythmias during hypoglycemia in patients with type 2 diabetes and cardiovascular risk. Diabetes 63, 1738–1747 (2014).

    Article  CAS  PubMed  Google Scholar 

  81. Goto, A., Arah, O. A., Goto, M., Terauchi, Y. & Noda, M. Severe hypoglycaemia and cardiovascular disease: systematic review and meta-analysis with bias analysis. BMJ 347, f4533 (2013).

    Article  PubMed  Google Scholar 

  82. Reno, C. M. et al. Severe hypoglycemia-induced lethal cardiac arrhythmias are mediated by sympathoadrenal activation. Diabetes 62, 3570–3581 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Tsujimoto, T. et al. Vital signs, QT prolongation, and newly diagnosed cardiovascular disease during severe hypoglycemia in type 1 and type 2 diabetic patients. Diabetes Care 37, 217–225 (2014).

    CAS  PubMed  Google Scholar 

  84. Tanenberg, R. J., Newton, C. A. & Drake, A. J. Confirmation of hypoglycemia in the 'dead-in-bed' syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr. Pract. 16, 244–248 (2010).

    Article  PubMed  Google Scholar 

  85. Razavi Nematollahi, L. et al. Proinflammatory cytokines in response to insulin-induced hypoglycemic stress in healthy subjects. Metabolism 58, 443–448 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Seaquist, E. R. et al. The impact of frequent and unrecognized hypoglycemia on mortality in the ACCORD study. Diabetes Care 35, 409–414 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. The Accord Study Group. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N. Engl. J. Med. 364, 818–828 (2011).

  88. Miller, M. E. et al. The effects of baseline characteristics, glycaemia treatment approach, and glycated haemoglobin concentration on the risk of severe hypoglycaemia: post hoc epidemiological analysis of the ACCORD study. BMJ 340, b5444 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Boussageon, R. et al. Effect of intensive glucose lowering treatment on all cause mortality, cardiovascular death, and microvascular events in type 2 diabetes: meta-analysis of randomised controlled trials. BMJ 343, d4169 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Zoungas, S. et al. Severe hypoglycemia and risks of vascular events and death. N. Engl. J. Med. 363, 1410–1418 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Fox, C. S. et al. Update on prevention of cardiovascular disease in adults with type 2 diabetes mellitus in light of recent evidence: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 38, 1777–1803 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Gill, G. V., Woodward, A., Casson, I. F. & Weston, P. J. Cardiac arrhythmia and nocturnal hypoglycaemia in type 1 diabetes — the 'dead in bed' syndrome revisited. Diabetologia 52, 42–45 (2009).

    Article  CAS  PubMed  Google Scholar 

  93. Desouza, C. V., Bolli, G. B. & Fonseca, V. Hypoglycemia, diabetes, and cardiovascular events. Diabetes Care 33, 1389–1394 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Amiel, S. A., Dixon, T., Mann, R. & Jameson, K. Hypoglycaemia in type 2 diabetes. Diabet. Med. 25, 245–254 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Feinkohl, I. et al. Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care 37, 507–515 (2014).

    Article  CAS  PubMed  Google Scholar 

  96. DiNardo, M., Noschese, M., Korytkowski, M. & Freeman, S. The medical emergency team and rapid response system: finding, treating, and preventing hypoglycemia. Jt. Comm. J. Qual. Patient Saf. 32, 591–595 (2006).

    Article  PubMed  Google Scholar 

  97. Korytkowski, M., DiNardo, M., Donihi, A. C., Bigi, L. & Devita, M. Evolution of a diabetes inpatient safety committee. Endocr. Pract. 12 (Suppl. 3), 91–99 (2006).

    Article  PubMed  Google Scholar 

  98. Umpierrez, G. E. et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 97, 16–38 (2012).

    Article  CAS  PubMed  Google Scholar 

  99. 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. 4, 3–15 (2009).

    Article  PubMed  Google Scholar 

  100. Noschese, M. et al. Effect of a diabetes order set on glycaemic management and control in the hospital. Qual. Saf. Health Care 17, 464–468 (2008).

    Article  CAS  PubMed  Google Scholar 

  101. Korytkowski, M., McDonnell, M. E., Umpierrez, G. E. & Zonszein, J. Patient guide to managing hyperglycemia (high blood sugar) in the hospital. J. Clin. Endocrinol. Metab. 97, 27A–28A (2012).

    Article  PubMed  Google Scholar 

  102. Moore, C. & Woollard, M. Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial. Emerg. Med. J. 22, 512–515 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Graveling, A. J. & Frier, B. M. Risks of marathon running and hypoglycaemia in type 1 diabetes. Diabet. Med. 27, 585–588 (2010).

    Article  CAS  PubMed  Google Scholar 

  104. Schabelman, E. & Kuo, D. Glucose before thiamine for Wernicke encephalopathy: a literature review. J. Emerg. Med. 42, 488–494 (2012).

    Article  PubMed  Google Scholar 

  105. Deusenberry, C. M., Coley, K. C., Korytkowski, M. T. & Donihi, A. C. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy 32, 613–617 (2012).

    Article  CAS  PubMed  Google Scholar 

  106. Fleseriu, M., Skugor, M., Chinnappa, P. & Siraj, E. S. Successful treatment of sulfonylurea-induced prolonged hypoglycemia with use of octreotide. Endocr. Pract. 12, 635–640 (2006).

    Article  PubMed  Google Scholar 

  107. Korytkowski, M. T. Diabetes and aging. Diabetes Spectrum. 26, 3–4 (2013).

    Article  Google Scholar 

  108. Little, S. A. et al. Recovery of hypoglycemia awareness in long-standing type 1 diabetes: a multicenter 2 × 2 factorial randomized controlled trial comparing insulin pump with multiple daily injections and continuous with conventional glucose self-monitoring (HypoCOMPaSS). Diabetes Care 37, 2114–2122 (2014).

    Article  CAS  PubMed  Google Scholar 

  109. Samann, A., Muhlhauser, I., Bender, R., Kloos, C. & Muller, U. A. Glycaemic control and severe hypoglycaemia following training in flexible, intensive insulin therapy to enable dietary freedom in people with type 1 diabetes: a prospective implementation study. Diabetologia 48, 1965–1970 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. Bott, S., Bott, U., Berger, M. & Muhlhauser, I. Intensified insulin therapy and the risk of severe hypoglycaemia. Diabetologia 40, 926–932 (1997).

    Article  CAS  PubMed  Google Scholar 

  111. Yeoh, E., Choudhary, P., Nwokolo, M., Ayis, S. & Amiel, S. A. Interventions that restore awareness of hypoglycemia in adults with type 1 diabetes: a systematic review and meta-analysis. Diabetes Care 38, 1592–1609 (2015).

    Article  PubMed  Google Scholar 

  112. Tylee, T. & Hirsch, I. B. Costs associated with using different insulin preparations. JAMA 314, 665–666 (2015).

    Article  CAS  PubMed  Google Scholar 

  113. Bergenstal, R. M., Welsh, J. B. & Shin, J. J. Threshold insulin-pump interruption to reduce hypoglycemia. N. Engl. J. Med. 369, 1474 (2013).

    Article  CAS  PubMed  Google Scholar 

  114. Baldwin, D. et al. A randomized trial of two weight-based doses of insulin glargine and glulisine in hospitalized subjects with type 2 diabetes and renal insufficiency. Diabetes Care 35, 1970–1974 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Thuzar, M., Malabu, U. H., Tisdell, B. & Sangla, K. S. Use of a standardised diabetic ketoacidosis management protocol improved clinical outcomes. Diabetes Res. Clin. Pract. 104, e8–e11 (2014).

    Article  PubMed  Google Scholar 

  116. Weinert, L. S. et al. Precipitating factors of diabetic ketoacidosis at a public hospital in a middle-income country. Diabetes Res. Clin. Pract. 96, 29–34 (2012).

    Article  PubMed  Google Scholar 

  117. Tan, H., Zhou, Y. & Yu, Y. Characteristics of diabetic ketoacidosis in Chinese adults and adolescents — a teaching hospital-based analysis. Diabetes Res. Clin. Pract. 97, 306–312 (2012).

    Article  PubMed  Google Scholar 

  118. Suwarto, S., Sutrisna, B., Waspadji, S. & Pohan, H. T. Predictors of five days mortality in diabetic ketoacidosis patients: a prospective cohort study. Acta Med. Indones. 46, 18–23 (2014).

    PubMed  Google Scholar 

  119. Ko, S. H. et al. Clinical characteristics of diabetic ketoacidosis in Korea over the past two decades. Diabet. Med. 22, 466–469 (2005).

    Article  PubMed  Google Scholar 

  120. Edo, A. E. Clinical profile and outcomes of adult patients with hyperglycemic emergencies managed at a tertiary care hospital in Nigeria. Niger. Med. J. 53, 121–125 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Guisado-Vasco, P. et al. Clinical features, mortality, hospital admission, and length of stay of a cohort of adult patients with diabetic ketoacidosis attending the emergency room of a tertiary hospital in Spain. Endocrinol. Nutr. 62, 277–284 (2015).

    Article  PubMed  Google Scholar 

  122. Alourfi, Z. & Homsi, H. Precipitating factors, outcomes, and recurrence of diabetic ketoacidosis at a university hospital in Damascus. Avicenna J. Med. 5, 11–15 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Lin, S. F., Lin, J. D. & Huang, Y. Y. Diabetic ketoacidosis: comparisons of patient characteristics, clinical presentations and outcomes today and 20 years ago. Chang Gung Med. J. 28, 24–30 (2005).

    CAS  Google Scholar 

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Acknowledgements

G.U. is supported in part by research grants from the American Diabetes Association (1-14-LLY-36), Public Health Service grant UL1 RR025008 from the Clinical Translational Science Award Program (M01 RR-00039), the NIH and the National Center for Research Resources. M.K. is supported in part by research grants from the NIH.

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G.U. and M.K. researched data for the article, made substantial contributions to discussions about the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Guillermo Umpierrez.

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G.U. declares that he has received consulting fees or/and honoraria for membership of advisory boards from Boehringer Ingelheim, Glytec, Johnson and Johnson, Merck, Novo Nordisk and Sanofi, and that he has received unrestricted research support for inpatient studies (to Emory University School of Medicine) from Astra Zeneca, Boehringer Ingelheim, Merck, Novo Nordisk and Sanofi. M.K. declares no competing interests.

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Umpierrez, G., Korytkowski, M. Diabetic emergencies — ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nat Rev Endocrinol 12, 222–232 (2016). https://doi.org/10.1038/nrendo.2016.15

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