There are multiple factors that promote disturbances in carbohydrate, protein, and lipid metabolism that ultimately lead to hyperglycemia and ketosis, the hallmark of DKA. In the absence of insulin, hepatic glucose production increases while glucose utilization in muscle and adipose tissue decreases. increased counter-regulatory hormone concentrations promote further hepatic gluconeogenesis and glycogenolysis. These metabolic processes combined lead to hyperglycemia. Hyperglycemia saturates the renal threshold for glucose reabsorption, causing glucosuria which causes osmotic diuresis, leading to dehydration and electrolyte loss. Hyperosmolarity and impaired renal function (pre-renal failure) may sometimes occur. Insulin deficiency and increased counter-regulatory hormones promote lipolysis, resulting in free fatty acid and glycerol production. Glycerol is used as precursor for glucose production in the process of gluconeogenesis, whereas free fatty acids are used for ketone production (ketogenesis).

A high glucagon-to-insulin ratio results in decreased malonyl co-enzyme A (CoA) concentrations, an intermediary product in the synthesis of long-chain fatty acids. Carnitine palmitoyl acetyltransferase (CPT1), a key enzyme in ketogenesis, is stimulated by low levels of malonyl CoA leading to enhanced production of ketone bodies by the liver (15-17). Ketone bodies, which include acetoacetate and ^-hydroxybutyrate, are weak acids; as bicarbonate buffers these acids, the alkali reserves dwindle and ketone body accumulation results in ketoacidosis. since these acids are unmeasured anions, this type of acidosis is called an "anion-gap acidosis." Figure 1 illustrates the pathogenesis of DKA and the hyperglycemic hyperosmolar state (HHS). HHS will be reviewed in a later section.

PRESENTATION Clinical Characteristics

DKA can present with mild-to-severe symptoms. Patients may complain of symptoms related to hyperglycemia and glucosuria such as polyuria and polydipsia. As a consequence of the increased urinary water loss, patients may present with signs of dehydration, such as tachycardia and dry mucus membranes. in severe cases, hypotension, due to volume depletion may occur. vomiting, abdominal pain, malaise, and weight loss are common presenting symptoms in ketoacidosis. signs related to the ketoacidotic

Absolute Insulin Deficiency

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