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Diabetic ketoacidosis in type 2 diabetes mellitus—pathophysiology and clinical presentation

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 730–731 (2007)Cite this article

Diabetic ketoacidosis (DKA) is traditionally considered a key clinical feature of type 1 diabetes mellitus (T1DM). Contrary to popular belief, however, DKA is more common in patients with type 2 diabetes mellitus (T2DM). DKA can develop in patients with T2DM under conditions of stress, such as trauma, surgery, or infections. Second-generation antipsychotic agents, cocaine abuse, and poor adherence to antidiabetic therapy can also precipitate DKA.1 In addition, an increasing number of cases of DKA without a precipitating cause have been reported in children, adolescents, and adults with T2DM.2 The clinical presentation in such cases is acute (as in classical T1DM) with severe hyperglycemia; however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment. This Viewpoint describes the diagnostic criteria, precipitating causes, and pathogenesis of DKA in T2DM.

The mechanisms that trigger DKA in T2DM are multifactorial, and include reduced secretion and action of insulin, and raised levels of anti-insulin (i.e. counter-regulatory) hormones. Elevated levels of glucagon, cortisol, and catecholamines act on the liver to increase glucose production via glycogenolysis and gluconeogenesis. In peripheral tissues, the combination of low insulin levels and high levels of catecholamines, cortisol, and growth hormone results in impaired glucose uptake. Increased levels of counter-regulatory hormones also lead to enhanced lipolysis with the production of increased amounts of free fatty acids. Acute elevations of plasma free fatty acids produce dose-dependent insulin resistance in skeletal muscle and liver. In addition, elevated levels of free fatty acids can inhibit glucose-stimulated insulin secretion at the level of the β cell. This constellation of negative effects of free fatty acids on carbohydrate metabolism is termed lipotoxicity.3

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Acknowledgements

SN Davis is supported by research grants from the NIH. GE Umpierrez is supported by research grants from the NIH, the American Diabetes Association, and the American Heart Association.

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  1. SN Davis is a Professor of Medicine and Molecular Physiology and Biophysics at Vanderbilt University School of Medicine, Nashville, TN, USA,

    Stephen N Davis

  2. GE Umpierrez is an Associate Professor of Medicine in the Division of Endocrinology and Metabolism, Emory University School of Medicine, Atlanta, GA, USA.,

    Guillermo E Umpierrez

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Correspondence to Stephen N Davis.

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Davis, S., Umpierrez, G. Diabetic ketoacidosis in type 2 diabetes mellitus—pathophysiology and clinical presentation. Nat Rev Endocrinol 3, 730–731 (2007). https://doi.org/10.1038/ncpendmet0641

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