C h a p t e r 3 3
Diabetes Mellitus and the Metabolic Syndrome
811
rapid breakdown of energy stores from muscle and fat
deposits, leading to increased movement of amino acids
to the liver for conversion to glucose and of fatty acids
for conversion to ketones. In the presence of ketosis,
the levels of glucagon and counterregulatory hormones
(i.e., glucocorticosteroids, epinephrine, and growth hor-
mone) are consistently increased. Furthermore, in the
absence of insulin, peripheral utilization of glucose and
ketones is reduced. Metabolic acidosis is caused by the
excess ketoacids that require buffering by bicarbonate
ions; this leads to a marked decrease in serum bicarbon-
ate levels.
The definitive diagnosis of DKA consists of
hyperglycemia
(blood glucose levels >250 mg/dL
[13.8 mmol/L]), low serum bicarbonate, low arterial
pH, and positive urine and serum ketones. It can be
further subdivided into
mild DKA
(serum bicarbon-
ate of 15 to 18 mEq/dL [15 to 18 mmol/L], pH 7.25
to 7.30);
moderate DKA
(serum bicarbonate 10 to
<15 mEq/dL [10 to <15 mmol/L], pH 7.00 to 7.24);
and
severe DKA
(serum bicarbonate <10 mEq/dL
[<10 mmol/L], pH <7.00).
40,41
Hyperglycemia leads
to osmotic diuresis, dehydration, and a critical loss
of electrolytes. Hyperosmolality of extracellular flu-
ids from hyperglycemia leads to a shift of water and
potassium from the intracellular to the extracellular
compartment. Extracellular sodium concentration fre-
quently is low or normal despite enteric water losses
because of an intracellular–extracellular fluid shift.
This dilutional effect is referred to as
pseudohypona-
tremia.
Serum potassium levels may also be normal or
elevated, despite total potassium depletion resulting
from protracted polyuria and vomiting.
The development of DKA is commonly preceded by
a day or more of polyuria, polydipsia, nausea, vomiting,
and marked fatigue, with eventual stupor that can prog-
ress to coma. Abdominal pain and tenderness may be
experienced without abdominal disease. The breath has
a characteristic fruity smell because of the presence of
volatile ketoacids. Hypotension and tachycardia may be
present because of a decrease in blood volume. A number
of the signs and symptoms that occur in DKA are related
to compensatory mechanisms. The heart rate increases
as the body compensates for a decrease in blood vol-
ume, and the rate and depth of respiration increase (i.e.,
Kussmaul respiration) as the body attempts to prevent
further decreases in pH. Metabolic acidosis is discussed
further in Chapter 8.
The goals in treating DKA are to improve circulatory
volume and tissue perfusion, decrease blood glucose,
and correct the acidosis and electrolyte imbalances.
These objectives usually are accomplished through the
Decreased glucose uptake
Protein breakdown
Amino acids
Glycogen
Glucose
Gluconeogenesis
Ketones
Glycerol
FFA
Lipolysis
Water,
electrolyte loss
Dehydration
Circulatory failure
Osmotic
diuresis
CNS depression
Coma
Insulin deficiency
(and glucagon excess)
Hyperglycemia
Metabolic
acidosis
FIGURE 33-10.
Mechanisms of diabetic
ketoacidosis. Diabetic ketoacidosis
is associated with very low insulin
levels and extremely high levels
of glucagon, catecholamines, and
other counterregulatory hormones.
Increased levels of glucagon and the
catecholamines lead to mobilization
of substrates for gluconeogenesis and
ketogenesis by the liver. Gluconeogenesis
in excess of that needed to supply
glucose to the brain and other glucose-
dependent tissues produces a rise in
blood glucose levels. Mobilization of free
fatty acids (FFAs) from triglyceride stores
in adipose tissue leads to accelerated
ketone production and ketosis. CNS,
central nervous system.
