Aetiology
The aetiology of inpatient hyperglycaemia is multi-factorial and often involves increases in circulating concentrations of stress hormones, which may contribute to harmful effects on vascular, haemodynamic, and immune systems.[16] In some cases, hyperglycaemia may be due to concomitant therapy, such as corticosteroids, or from nutritional support, including parenteral, and occasionally enteral, nutrition. Hyperglycaemia has been associated with an increased risk of complications and mortality in patients on parenteral nutrition.[17]
Hypoglycaemia - a fall in blood glucose to below 3.9 mmol/L (70 mg/dL) - can be either iatrogenic or spontaneous, and can result from underlying medical illness, even in the absence of antidiabetic agents.[8] In patients with diabetes, it is a well-recognised adverse effect of insulin and certain oral antihyperglycaemic drugs, particularly sulfonylureas. Errors in the prescribing and administration of insulin are a frequent cause of inpatient hypoglycaemia, such as misreading a handwritten ‘U’ for units as a zero (e.g., 4U interpreted as 40 units) or confusing the insulin name with the dose (e.g., Humalog Mix25 mistaken for Humalog 25 units).[18][19] The use of electronic prescribing has been linked to a reduced rate of such errors.[20] Other risk factors for hypoglycaemia include: previous episodes of severe hypoglycaemia; recent or frequent hospitalisations; increased duration of diabetes; reduced nutritional intake, interruptions in parenteral or enteral nutrition, malnutrition, or lack of synchronisation between meal timing and hypoglycaemic drugs; renal or hepatic impairment; heart failure; malignancy; infection; sepsis; older age; polypharmacy; cognitive impairment; hypothermia; respiratory failure and mechanical ventilation; and intoxications that affect glucose regulation (e.g., alcohol, tramadol, amphetamines, hydroxychloroquine).[1][3][4][8][21] Hormonal deficiencies - such as adrenal insufficiency, hypopituitarism, hypothyroidism, glucagon deficiency, and catecholamine withdrawal after pheochromocytoma resection - are also risk factors.[22]
Pathophysiology
Hyperglycaemia in patients admitted to hospital, regardless of prior diabetes status, is a complex condition, typically involving both insulin resistance and insulin deficiency, as well as increased hepatic glucose production. Insulin resistance is commonly driven by inflammation, triggered by infections or stress hormones (such as cortisol, catecholamines, glucagon, and growth hormone) and cytokines. These same factors can also impair pancreatic beta-cell function, contributing to insulin deficiency.
Certain treatments can further exacerbate hyperglycaemia. For example, corticosteroids induce insulin resistance, and parenteral nutrition - especially with a high fat content - can elevate free fatty acid levels, which disrupt glucose metabolism.[23]
Hyperglycaemia has multiple physiological consequences that may negatively impact clinical outcomes. These include impaired white blood cell function, altered blood flow and vascular reactivity, and increased oxidative stress.
Hypoglycaemia in hospitalised patients results from a complex interplay of factors disrupting normal glucose homeostasis. In critically unwell patients, metabolic stress increases tissue glucose utilisation while simultaneously impairing gluconeogenesis and glycogenolysis, leading to a net deficit in circulating glucose.[22] Organ dysfunction, particularly of the liver and kidneys, further compromises glucose production and clearance of insulin and hypoglycaemic agents.[22] Endocrine abnormalities such as adrenal insufficiency, hypopituitarism, and hypothyroidism reduce counter-regulatory hormone secretion, diminishing the body’s ability to raise blood glucose during hypoglycaemic episodes.[22] Additional contributors include inadequate nutritional intake, altered drug regimens, and pharmacological effects of certain drugs that increase insulin secretion or sensitivity.[8] Collectively, these factors impair the physiological responses designed to prevent and correct hypoglycaemia, increasing the risk of neuroglycopaenia and adverse clinical outcomes in the inpatient setting.[22]
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