Epidemiology
The precise prevalence and incidence of hyperosmolar hyperglycaemic state (HHS) is difficult to determine because of the lack of population-based studies and the multiple comorbidities often found in these patients. However, the overall prevalence is estimated at less than 1% of all diabetes-related hospital admissions.[5][11]
HHS is seen most commonly in older people with poorly controlled type 2 diabetes.[3][13] However, HHS is now being seen in younger adults and even in children/teenagers, often as the initial presentation of type 2 diabetes.[6]
Mortality rates in HHS have been reported to be 5% to 20%, a rate that is 10-fold higher than that reported for diabetic ketoacidosis.[1][13] Mortality increases significantly when the patient is above the age of 70 years.[14] A combined state of severe hyperglycaemia, hyperosmolality, and metabolic acidosis is seen in approximately 24% to 33% of all hyperglycaemic emergencies.[5][15][16]
Risk factors
Infection is the major precipitating factor, occurring in 40% to 60% of patients.[9] Pneumonia and urinary tract infections are most commonly reported.[3][9][17]
Counter-regulatory hormones, particularly adrenaline (epinephrine), are increased as a systemic response to infection. They induce insulin resistance, decrease insulin production and secretion, and increase lipolysis, ketogenesis, and volume depletion, thereby contributing to the hyperglycaemic crises in patients with diabetes.[1][11]
Non-adherence to insulin or oral antidiabetic medication is common in patients admitted with HHS.[3] In the US, this association is much higher in urban African-American patients with diabetes, in whom non-adherence is the sole reason for HHS in 42% of cases.[25]
Alcohol and cocaine misuse is a major contributing factor to non-adherence of diabetic therapy. In one study of urban, underprivileged, African-American patients with HHS, alcohol misuse was seen in 44% of patients and cocaine use was seen in 9%.[25]
Reduction in the net effective concentration of insulin produces a relative insulin deficiency. If this deficiency is significant enough it can trigger HHS.[1][11]
Underlying cardiovascular events, particularly myocardial infarction, provoke the release of counter-regulatory hormones that may result in HHS.[1][11]
Acute stroke is associated with increased levels of counter-regulatory hormones and compromised access to water and insulin, which may contribute to the development of hyperglycaemic crises.[11]
Nursing home residents are often bedridden or have restricted mobility, which reduces their access to water intake and increases the risk of volume depletion and HHS. Other contributing factors are altered thirst mechanisms, comorbidities, polypharmacy, and possible failure to detect hyperglycaemia or inappropriate treatment of diabetes.[9][39]
In patients with diabetes, failure to detect hyperglycaemia or inappropriate treatment of diabetes can lead to the development of HHS.
Patients with poorly controlled diabetes who receive enteral or parenteral nutrition or dextrose-containing fluids may develop severe hyperglycaemia, which can trigger HHS.[18][40][41] Failure to initiate insulin therapy postoperatively to correct hyperglycaemia exacerbates the risk.
Neurosurgical procedures are also associated with increased risk of HHS, although it remains unclear whether this is a result of direct central nervous system injury, solute load, or treatment with drugs such as glucocorticoids or phenytoin.[9][18]
Corticosteroids, thiazide diuretics, beta-blockers, phenytoin, and didanosine are thought to induce HHS by affecting carbohydrate metabolism.[1][9][11][24][26][27][28][29][30][31]
Atypical antipsychotic medications (in particular, clozapine and olanzapine) have also been implicated in producing diabetes and hyperglycaemic crises.[9][32][33] Possible mechanisms include induction of peripheral insulin resistance; a direct influence on pancreatic beta-cell function by 5-HT1A/2A/2C receptor antagonism; inhibitory effects through alpha2-adrenergic receptors, or by toxic effects.[33]
Hyperthyroidism induces glucose intolerance by lowering insulin levels and peripheral insulin sensitivity.[21] Circulating thyroid hormones affect glycogenolysis and enhance gluconeogenesis in the liver, which can contribute to the development, and exacerbation of, diabetes.[42] A case series of HHS in hyperthyroidism has been reported.[43]
A few cases of HHS associated with acromegaly have been reported.[20]
Use of this content is subject to our disclaimer