Medico

Diabetes

FounDation

Hyperglycemic Crisis in Adults: Pathophysiology,
Presentation, Pitfalls, and Prevention
Michael Fowler, MD

Editor’s note: This article is the 9th in
a 12-part series reviewing the fundamentals of diabetes care for physicians
in training. Previous articles in the
series can be viewed at the Clinical
Diabetes website (http://clinical.
diabetesjournals.org).
Thepatients never stop making
water and the flow is incessant . . . .
Life is short, unpleasant and painful,
thirst unquenchable, drinking excessive . . . . If for a while they abstain
from drinking, their mouths become
parched and their bodies dry; the
viscera seem scorched up: the patients
are affected by nausea, restlessness
and a burning thirst, and within a
short time, they expire.—Areteus, 3rd century1

D

iabetic ketoacidosis (DKA)
and hyperosmolar hyperglycemic state (HHS) are
acute and potentially life-threatening
complications of diabetes. Although
they have important differences, they
both occur because of lack of insulin effect and can be considered two
manifestations of the same underlying mechanism: insulin deficiency.
Typically, patients with type 1 diabetesare more likely to exhibit DKA
because of their absolute insulin
deficiency, and patients with type 2
diabetes are more likely to experience
HHS because of the presence of some
insulin secretion. However, a signifi-

CliniCal Diabetes • Volume 27, Number 1, 2009

cant number of patients stray from
these patterns.2–4
Both of these conditions carry
significant likelihood of morbidityand mortality, including cerebral
edema, permanent neurological
injury, and death. In large centers,
the mortality rate for DKA is < 5%.
However, the mortality rate for
HHS is ~ 11%.4 With the potential
for mortality and an incidence of
~ 100,000 cases of DKA per year,
general physicians and physicians
in training will be treating patients
with these acute complications
of diabetes notinfrequently. It is
important to be familiar with the
pathophysiology, presentation, treatment, complications, and—perhaps
most importantly—prevention of
DKA and HHS.
Pathophysiology
The basic cause of DKA and HHS is
insufficient insulin effect. Combined
with the insufficiency of insulin
effect, there is an increase in counterregulatory hormone levels, including
glucagon, cortsol,catecholamines,
and growth hormone. Both factors
contribute to hyperglycemia.
DKA and HHS may also be
thought of as occurring on a spectrum of disease manifestation. On
one end of the spectrum lie absolute
insulin deficiency and profound
ketosis and acidosis, which is DKA.
DKA tends to occur in patients
with type 1 diabetes, who, because
of destruction of β -cells, exhibit
absolute insulindeficiency. On the

other end of the spectrum is extreme
hyperglycemia without ketosis and
acidosis.4 This tends to occur in
patients with type 2 diabetes who
still produce enough endogenous
insulin to suppress ketosis but not
enough to control hyperglycemia.
As the analogy implies, patients may
present with various manifestations
of both disorders. For example, a
patient with DKA mayhave used
enough insulin to partially suppress
ketosis but still manifest profound
hyperglycemia. Patients with HHS
may also have varying degrees of
ketosis and mild acidosis, depending on the degree to which they have
been able to produce insulin and the
extent of associated factors such as
dehydration.2–5
Insulin deficiency causes a lack
of glucose utilization in insulindependent tissuessuch as muscle
and adipose and therefore leads to
hyperglycemia. Lack of insulin also
stimulates hyperglycemia by increasing hepatic gluconeogenesis. This is
a common mechanism in both DKA
and HHS.
Deprived of glucose utilization,
the body must look elsewhere for
fuel to survive. In addition to hyperglycemia, lack of insulin increases
degradation of triglycerides into free
fatty...