Pathophysiology
Elevated levels of counterregulatory hormones (glucagon, catecholamines, cortisol, and growth hormone) initiate HHS by stimulating hepatic glucose production through glycogenolysis and gluconeogenesis, leading to hyperglycaemia, intracellular water depletion, and subsequent osmotic diuresis. High levels of catecholamines combined with low levels of insulin reduce peripheral glucose uptake. Glycosuria causes greater loss of water than of sodium, resulting in hyperosmolarity and dehydration. Decreased intravascular volume, often combined with underlying renal disease, decreases the glomerular filtration rate, thereby decreasing glucose clearance and further increasing blood glucose levels.
Although the insulin level is not adequate to control blood glucose, it can suppress lipolysis and ketogenesis5.Proinflammatory cytokines (e.g., tumour necrosis factor α, interleukin β, interleukin-6, interleukin-8), plasminogen activator inhibitor-1, reactive oxygen species, and lipid peroxidation increase two- to threefold during the acute crisis, but return to normal within 24 hours. These increases create a temporary prothrombotic environment that increases the risk of vascular occlusion, mesenteric artery thrombosis, myocardial infarction, low-flow syndrome, disseminated intravascular coagulopathy, cerebrovascular accident, and bilateral femoral artery thrombosis. Figure 114.
