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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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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