From the Guidelines
Diabetic ketoacidosis (DKA) is primarily caused by a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, leading to increased hepatic and renal glucose production and impaired glucose utilization in peripheral tissues, resulting in hyperglycemia, ketonemia, and metabolic acidosis. The pathophysiology of DKA involves a complex interplay of hormonal alterations, including a decrease in insulin levels and an increase in counterregulatory hormones such as glucagon, catecholamines, cortisol, and growth hormone 1. This leads to:
- Increased hepatic and renal glucose production
- Impaired glucose utilization in peripheral tissues
- Hyperglycemia and changes in osmolality of the extracellular space
- Release of free fatty acids into the circulation from adipose tissue (lipolysis)
- Unrestrained hepatic fatty acid oxidation to ketone bodies (-hydroxybutyrate [-OHB] and acetoacetate), resulting in ketonemia and metabolic acidosis 1. The combination of insulin deficiency and increased counterregulatory hormones in DKA also leads to glycosuria, causing osmotic diuresis, with loss of water, sodium, potassium, and other electrolytes 1. Key factors contributing to the development of DKA include:
- Inadequate insulin levels
- Increased counterregulatory hormones
- Hyperglycemia
- Ketonemia
- Metabolic acidosis
- Electrolyte imbalances
- Dehydration.
From the Research
Pathophysiology of Diabetic Ketoacidosis (DKA)
The pathophysiology of DKA is attributed to a combination of two hormonal abnormalities: a relative insulin insufficiency and stress hormone excess (glucagon, catecholamines, cortisol, and growth hormone) 2. This leads to impaired carbohydrate utilization and ketonaemia, resulting in metabolic acidosis 3, 2. The reduction in effective insulin action combined with increased counterregulatory hormones is a basic common pathophysiological mechanism in DKA 4.
Key Factors Contributing to DKA
- Insulin deficiency, which can be due to withdrawal of exogenous insulin, pancreatic beta-cell failure, or insulin resistance 2
- Stress hormone excess, which can be caused by factors such as fasting, stress, and dehydration 2
- Increased lipolysis and production of excess fatty acids, leading to beta-oxidation and ketogenesis 4
- Impaired glucose utilization, resulting in hyperglycemia and metabolic acidosis 3, 2
Consequences of DKA
- Metabolic acidosis with loss of water through acidotic breaths 2
- Rise in plasma lipids, hyperglycemia, and glycosuria, leading to osmotic diuresis and further loss of water 2
- Excretion of partly neutralised ketoacids via the kidney, with loss of cations (Na+ and K+) 2
- Net increase in protein catabolism, leading to an increased amino acid flux from muscle and an enhanced load of gluconeogenic precursor to the liver 2