Elevated Lipase and Diabetic Ketoacidosis

Savio Reddymasu, Elias Bahta, Steven Levine, Kenneth Manas, Larry E Slay
Department of Medicine, LSU Health Sciences Center. Shreveport, Louisiana, USA
ABSTRACT
Context Atypical antipsychotic agents are
associated with diabetes mellitus and
pancreatitis.
Aripiprazole,
a
new
antipsychotic, has never been implicated to
cause either diabetes mellitus or pancreatitis.
We present a patient who developed diabetes
mellitus after being started on aripiprazole.
Case report: A 33 year-old male with
schizophrenia presented with fatigue,
dyspepsia and epigastric pain. Patient was
found to have hyperglycemia, diabetic
ketoacidosis, and hyperlipasemia. Imaging
studies of the pancreas were normal. Patient
was started on aripiprazole treatment 18
months prior to this episode and had
experienced progressive weight gain since
then. Work up for other causes of pancreatitis
was negative.
Conclusions Diabetes mellitus in this patient
was probably a complication of aripiprazole
due to progressive weight gain. In the absence
of radiologic evidence of pancreatitis,
hyperlipasemia was probably secondary to
diabetic ketoacidosis. Possible causes of
hyperlipasemia and its significance in diabetic
ketoacidosis are discussed.
INTRODUCTION
Aripiprazole is a relatively new antipsychotic
drug approved to treat schizophrenia and
considered to have the least side affects
among all the atypical antipsychotics [1, 2].
Other atypical antipsychotic agents including
clozapine, olanzapine, quetiapine, risperidone,
and ziprasidone are associated with diabetes,
neuroleptic malignant syndrome, pancreatitis
and weight gain [3]. We present a patient who
had diabetic ketoacidosis and elevated lipase
with aripiprazole.
CASE REPORT
A 33-year-old African American male with
schizophrenia presented to the Emergency
Department with complains of fatigue,
dyspepsia and epigastric abdominal pain. At
presentation his body mass index (BMI) was
41 kg/m
2
(reference range: 18.5-24.9 kg/m
2
)
and he had a blood glucose of 1,769 mg/dL
(reference range: 70-105 mg/dL), anion gap
of 32 mmol/L (reference range: 8-16
mmol/L), serum osmolality 373 mOsm/kg
(reference range: 275-300 mOsm/kg), CO6
mmol/L (reference range: 18-29 mmol/L),
amylase 182 IU/L (reference range: 20-125
IU/L), lipase 4,068 IU/L (reference range: 8-
78 IU/L), serum triglycerides 184 mg/dL
(reference range: 40-150 mg/dL), calcium 8.5
mg/dL (reference range: 8.9-10 mg/dL).
Thyroid function tests were normal. No prior
history of diabetes mellitus, pancreatitis,
cholelithiasis or substance abuse was
obtained. Family history for diabetes mellitus
was negative. Treatment with aripiprazole
(Abilify
®
was initiated 18 months ago prior
to admission. Since that time, the patient had

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 7, No. 3 - May 2006. [ISSN 1590-8577]
304
experienced progressive weight gain. His
BMI was 32 kg/m
2
prior to starting the
medication. Computerized tomography (CT)
and ultrasound of the abdomen were negative
for pancreatitis and gallstones. Patient was
treated with intravenous fluids and insulin.
Aripiprazole was discontinued. Patient was
discharged home on haloperidol and insulin
glargine. Diagnosis was diabetes induced by
aripiprazole and elevated lipase secondary to
diabetic ketoacidosis. After 6 months off of
aripiprazole his BMI decreased to 33 kg/m
2
.
Although he continued to be a diabetic, his
insulin requirements came down.
DISCUSSION
The pathophysiology of new onset diabetes in
atypical antipsychotic drug use is not clear. A
possible mechanism is insulin resistance due
to weight gain induced by these drugs [3].
The patient presented above had been gaining
weight ever since aripiprazole therapy was
initiated, which may explain his new onset
diabetes mellitus and diabetic ketoacidosis.
Incidence of diabetes mellitus is lowest with
aripiprazole, when compared to other
antipsychotics [1, 2, 4]. Timing of onset of
diabetes mellitus may vary from a few days
up to 4 years [4]. Metabolic complications
with atypical antipsychotics have commonly
been reported in African American patients
and often presentation is with diabetic
ketoacidosis, as in our patient [4, 5, 6, 7, 8].
We know of no studies that confirm this
association. Slightly elevated amylase and
grossly elevated lipase in our patient could
indicate pancreatitis, but negative imaging
studies of the pancreas weigh against this
diagnosis. It has been proposed that amylase
and lipase levels are elevated in 16-25% of
patients with diabetic ketoacidosis, especially
lipase. Elevated lipase in diabetic ketoacidosis
is not a reliable indicator of pancreatitis in the
presence of normal imaging studies of the
pancreas [9, 10]. There is a direct correlation
between the lipase level and the serum
osmolality in diabetic ketoacidosis [9], as in
this patient. There is no clear explanation for
the hyperlipasemia in diabetic ketoacidosis.
Possible mechanisms involved include
decreased excretion of lipase due to a lower
glomerular filtration rate in diabetic
ketoacidosis [11]. Non pancreatic lipolytic
enzymes produced by stomach, liver, small
intestine, or esophagus might be released into
circulation causing a elevated lipase level
[12]. We conclude that aripiprazole might
induce diabetes mellitus by causing weight
gain and it would be prudent to constantly
monitor patients weight and blood sugars as
long as the patient is on this drug.
Hyperlipasemia in this patient was due to
diabetic ketoacidosis and not secondary to
aripiprazole. In the absence of any structural
abnormalities of the pancreas, elevated lipase
is a non-specific indicator of pancreatitis in
diabetic ketoacidosis.
Received December 12
th
, 2005 - Accepted
January 20
th
, 2006
Keywords aripiprazole; Diabetic Ketoa-
cidosis; Lipase; Pancreatitis
Correspondence
Elias Bahta
LSU Health Sciences Center
1501 Kings Hwy
P.O. Box # 205
Shreveport, LA, 71115
USA
 
References
1. Swainston Harrison T, Perry CM. Aripiprazole: a
review of its use in schizophrenia and schizoaffective
disorder. Drugs 2004; 64:1715-36. [PMID 15257633]
2. Davies MA, Sheffler DJ, Roth BL. Aripiprazole: a
novel atypical antipsychotic drug with a uniquely
robust pharmacology. CNS Drug Rev 2004; 10:317-36.
[PMID 15592581]
3. Boehm G, Racoosin JA, Laughren TP, Katz R.
Consensus development conference on antipsychotic
drugs and obesity and diabetes: response to consensus
statement. Diabetes Care 2004; 27:2088-9. [PMID
15277452

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