similarity exists between the chemical structure of olanzapine and that of other
pancreatic toxins. Given the well-known potential for olanzapine to cause weight gain,
insulin resistance would appear more likely to develop in patients who experience glucose
dysregulation or weight gain. Another postulated mechanism is that atypical antipsychotic
agents may decrease the half-life or number of glucose transporters, thereby making fewer
transporters available to carry glucose, which would increase the amount of glucose in the
{*filter*}.[17]
Clinical studies and case reports suggest that weight gain and other risk factors may
contribute to development of insulin resistance or diabetes. A study of 14 patients with
psychosis examined the effects of olanzapine treatment for an average of 5 months.[18]
Olanzapine was associated with weight gain in 12 of the 14 patients and with fasting
hyperglycemia in 3. In addition, 10 had elevated insulin levels and 8 had hyperleptinemia.
Weight change correlated positively with {*filter*} glucose levels, and leptin levels
correlated with insulin levels. These data suggest that olanzapine-induced weight gain and
insulin resistance may be the mechanisms in some patients. These data are supported by the
fact that olanzapine-associated hyperosmolar states (glucose levels > 1000 mg/dl) in which
acidosis was absent have been reported.[19] This would suggest that some endogenous
production of insulin takes place. In other patients, such as in our patient, acidosis did
not indicate a requirement for maintenance insulin therapy. Such cases would support a
type 2 diabetes presentation. Finally, the affinity of olanzapine for certain specific
receptors (i.e., serotonergic and histaminic antagonism) may contribute to the risk of
diabetes in vulnerable patients.[12] Given that undiagnosed diabetes is prevalent,
olanzapine may be precipitating or unmasking diabetes in vulnerable patients who already
have risk factors or previously undiagnosed diabetes.

As in other patients, our patient was diagnosed with diabetes incidentally while taking
olanzapine. Also, as with our patient, diagnosis of diabetes may be delayed until
complications such as ketoacidosis or hyperosmolar states occur. Our patient was
hospitalized after weeks of acute symptomatic hyperglycemia, and his mental illness likely
interfered with his insight and symptom detection. Although we suspect that our patient
had ketoacidosis, we cannot confirm this because measurements of serum osmolality, serum