Diabetic ketoacidosis
Epidemiology
In England, the incidence of hospital admissions for DKA among adults with type 2 diabetes increased 4.24% annually between 1998 and 2013; hospitalisations for DKA in adults with type 1 diabetes increased from 1998 to 2007, and remained static until 2013.[10]
In Denmark, the annual incidence of DKA in the general population was estimated to be 12.6/100,000 during the period 1996 to 2002, and was higher in men than in women (14.4 versus 11.4 per 100,000, p<0.0001).[11] Twelve percent of patients, typically those aged over 50 years, were diagnosed with type 2 diabetes. Overall mortality was 4%.[11] In Brazil, DKA was reported in 32.8% of patients at diagnosis of type 1 diabetes.[12] DKA at diagnosis was more common in non-white than in white people.[12]
In the US from 2000 to 2009, the rate of hospitalisations for DKA decreased overall, from 21.9 to 19.5 per 1000 persons with diabetes, but then increased in the period 2009 to 2014 to 30.2 per 1000 persons with diabetes.[13] In 2014, rates of hospitalisation for DKA were highest among people aged <45 years (44.3 per 1000 persons with diabetes), and decreased with age (5.2 per 1000 persons with diabetes aged 45 to 64 years; 1.6 per 1000 persons aged 65 to 74 years; and 1.4 per 1000 persons aged ≥75 years).[13] During the period 2000 to 2014, in-hospital mortality rates among people with DKA consistently decreased, from 1.1% to 0.4%.[13] In 2014, about 207,000 accident and emergency department visits for people aged 18 years or older in the US were for hyperglycaemic crises (e.g., DKA, hyperglycaemic hyperosmolar state).[14]
Risk factors
Reduction in the net effective concentration of insulin leads to impaired carbohydrate, lipid, and ketone metabolism in DKA. Decreased insulin results in increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilisation by peripheral tissues.[1]
Non-compliance with insulin therapy has been found to be the leading precipitating factor in black people,[26] and is present in over 30% of patients with DKA.[16] Psychological and social factors may impact on glycaemic control, and low socio-economic status is correlated with a higher risk for DKA.[27][28]
The most common precipitating factor in DKA is infection. Increased counter-regulatory hormones, particularly adrenaline, as a systemic response to infection lead to insulin resistance, increased lipolysis, ketogenesis, and volume depletion, which may contribute to the development of hyperglycaemic crises in patients with diabetes.[1]
Acute medical events such as stroke, with increased levels of counter-regulatory hormones and compromised access to water and insulin, may contribute in the development of hyperglycaemic crises.[1]
Hormonal derangements in some endocrine glands lead to increased counter-regulatory hormones and development of DKA in patients with concomitant diabetes.[31]
Hormonal derangements in some endocrine glands lead to increased counter-regulatory hormones and development of DKA in patients with concomitant diabetes.[32]
Drugs that affect carbohydrate metabolism may precipitate hyperglycaemic crises.[18][33][34][35] A recent report suggests that cocaine abuse is an independent risk factor associated with recurrent DKA.[36][37]
Sodium-glucose co-transporter-2 (SGLT2) inhibitors (e.g., canagliflozin, dapagliflozin, empagliflozin), used for glycaemic control of type 2 diabetes, have been the subject of a US Food and Drug Administration warning about a risk for DKA.[38]
Immune checkpoint inhibitor therapy for cancer (PD-1 and PD-L1 blocking antibodies such as nivolumab, pembrolizumab and avelumab) appears to be associated with a risk for DKA and type 1 diabetes mellitus.[39][40][41]
Hypercortisolism leads to insulin resistance and may occasionally precipitate DKA in patients with concomitant diabetes; it more commonly precipitates hyperosmolar hyperglycaemic state.
Ancestry plays a role in ketosis-prone diabetes, with DKA a presenting manifestation of undiagnosed type 2 diabetes in young adults. Approximately 80% of obese black patients with DKA have type 2 diabetes, characterised by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association compared with lean patients with type 1 diabetes.[6]
DKA has been reported in patients with type 1 diabetes who have had bariatric surgery.[42]
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