Case Report
STEROID-INDUCED DIABETIC KETOACIDOSIS IN
A PATIENT WITH TYPE 2 DIABETES MELLITUS
Abhinav Tiwari, MD1; Hussain Al-Robeh, MD1; Himani Sharma, MD1;
Zaid Ammari, MD1; Mohammad Saud Khan, MD1; Juan Carlos Jaume, MD2
ABSTRACT
Objective: Diabetic ketoacidosis (DKA) is usually
associated with type 1 diabetes mellitus; however, it is
increasingly being recognized in patients with type 2
diabetes mellitus (T2DM). Triggering factors usually
involve infections and poor medication adherence. Other
potential triggers are myocardial infarction, antipsychotic
drug usage, malignancy, and cerebrovascular accidents. No
case of steroid-induced DKA in a patient with T2DM has
been reported in the literature.
Methods: Clinical and laboratory data are presented.
Results: We present a case of a middle-aged patient
with a history of well-controlled T2DM via metformin.
The patient was started on oral prednisone for lumbar disc
herniation, and then presented with acute DKA. No other
trigger for DKA but steroid initiation was found.
Conclusion: We conclude that patients with diabetes
who receive glucocorticoids should be monitored careful-
ly, as steroids can precipitate DKA. This may occur in the
absence of any other triggering factor, and even in patients
with well-controlled T2DM. (AACE Clinical Case Rep.
2018;4:e131-e133)
Submitted for publication June 1, 2017
Accepted for publication July 25, 2017
From the 1Department of Internal Medicine, University of Toledo Medical
Center, Toledo, Ohio, and 2Department of Endocrinology, University of
Toledo Medical Center, Toledo, Ohio.
Address correspondence to Dr. Abhinav Tiwari, University of Toledo
Medical Center, 3000 Arlington Avenue, MS 1150, Toledo, OH 43614.
E-mail: abhinav.tiwari@utoledo.edu.
DOI:10.4158/EP171984.CR
To purchase reprints of this article, please visit: www.aace.com/reprints.
Copyright © 2018 AACE.
Copyright © 2018 AACE AACE CLINICAL CASE REPORTS Vol 4 No. 2 March/April 2018 e131
Abbreviations:
DKA = diabetic ketoacidosis; T2DM = type 2 diabetes
mellitus
INTRODUCTION
Although diabetic ketoacidosis (DKA) has tradi-
tionally been associated with type 1 diabetes mellitus, it
is increasingly being recognized in patients with type
2 diabetes mellitus (T2DM). Triggering factors leading
to DKA in T2DM, although not obvious in many cases,
usually involve infections and poor medication adher-
ence. Other reported causes include myocardial infarction,
antipsychotic drug usage, malignancy (pancreatic adeno-
carcinoma), and cerebrovascular accidents (1-3). To our
knowledge, there is no specific, documented case report of
steroid-induced DKA in T2DM in the literature; however,
a retrospective study mentioned 1 case of steroid-induced
DKA in a study population of patients with T2DM (4).
Steroids can worsen insulin resistance, rendering
patients relatively insulin insufficient and unable to main-
tain a euglycemic state to prevent ketone production. Here
we present a case of DKA clearly precipitated by oral pred-
nisone in a 55-year-old, female patient with previously
well-controlled T2DM via an oral hypoglycemic agent.
CASE REPORT
A 55-year-old, African American female with a 5-year
history of well-controlled T2DM on metformin presented
to her primary care physician with pain in her left, lower
extremity and weakness for 3 weeks. Her mother also had
T2DM, which was well-controlled on oral agents. The
patient had chronic low back pain, which was controlled
by celecoxib. She denied any history of trauma or lifting
e132 Steroid-Induced DKA, AACE Clinical Case Rep. 2018;4(No. 2)
any heavy weights. She also denied any history of bowel
or bladder incontinence. Her physical exam results were
significant for tenderness over the lumbar spine, 3/5 motor
strength in her left, lower extremity, brisk knee reflexes,
and positive straight leg raise test. Due to her progres-
sive muscle weakness, a magnetic resonance imaging of
the lumbar spine was performed, which revealed severe
narrowing of the left neural foramina secondary to focal
disc protrusion at L3 and L4. The patient was started on 40
mg of prednisone twice daily.
One week later she presented to the emergency depart-
ment with a 1-day duration of lethargy, drowsiness, and
confusion. Upon examination, her body mass index was
48 kg/m2 and vital signs included blood pressure of 98/68
mm Hg, heart rate 104 beats/min, respiratory rate of 36
breaths/min and temperature of 36.5°C. Laboratory tests
revealed her sodium level was 138 mmol/L, potassium
was 4.1 mmol/L, creatinine was 1.28 mg/dL, bicarbon-
ate was 2 mmol/L (which is low), glucose was 696 mg/dL
(which is high), and an anion gap of 29. Arterial blood gas
tests yielded pH 7.1, pCO2 12.2 mm Hg, and serum beta
hydroxybutyrate of 4.5 mmol/L (normal range is 0.4 to 0.5
mmol/L). Her hemoglobin A1c level was 13.3%, which
had increased from 7% one month earlier, reflecting the
acutely decompensated hyperglycemic state.
She was started on regular insulin infusion and the
DKA protocol per our institution’s policy. There was no
apparent triggering factor for DKA except for the use of
steroids. Urine analysis, urine culture, and blood cultures
were all negative for infection. Chest X-ray was non-
revealing, and troponins remained normal. The patient
initially required high doses of intravenous insulin, as high
as 240 U/day, and needed insulin infusion for 3 days. The
patient recovered uneventfully and was transitioned to
subcutaneous basal insulin and metformin.
Due to the possibility of latent autoimmune diabetes
of adults, her serum glutamic acid decarboxylase and insu-
linoma-associated protein 2 antibodies were measured at
the next follow-up visit, which were negative however her
serum C-peptide was elevated at 3.5 nmol/L (normal range
is 0.26 to 1.03 nmol/L).
DISCUSSION
DKA, for a long time, has been considered a hallmark
of type 1 diabetes mellitus; however, more recently, this
condition has been increasingly recognized in patients
with T2DM and “ketosis-prone diabetes”. The occurrence
of DKA is due to relative or complete insulin deficiency,
which is not sufficient to prevent ketosis in the presence
of excess counterregulatory hormones (5). Insulin inhib-
its gluconeogenesis and glycogenolysis; however, insulin
is unable to effectively control glucogenic enzymes in
insulin-resistant states, leading to increased glucose output
from the liver (6).
Copyright © 2018 AACE
It was thought that patients with T2DM do not devel-
op ketoacidosis as there is almost always some residual
beta cell function in the pancreas, which could produce
sufficient amounts of insulin to prevent ketogenesis, but
inadequate to control blood glucose (7). The occurrence
of DKA in T2DM has been related to the presence of
coexisting stressors such as infections, cardiovascular or
cerebrovascular events, or due to sudden discontinuation
of insulin therapy (1). Although not due to steroids, DKA
has been reported to be the initial presentation of T2DM in
adolescents (8). Other triggering factors have been report-
ed including antipsychotic drug usage, pregnancy, alcohol
consumption, and malignancy (pancreatic adenocarci-
noma) (1-3). Several medications have also been known
to trigger DKA including high-dose thiazide diuretics,
second-generation antipsychotic agents, and sympathomi-
metic agents (e.g. dobutamine and terbutaline) (9,10).
Furthermore, there have been reports of ketoacidosis
associated with sodium-glucose cotransporter 2 inhibitors
(11). However, a meta-analysis in 2017 compared 72 trials
of sodium-glucose cotransporter 2 inhibitors that reported
information about DKA and found no significant increased
risk for ketoacidosis with inhibitor use either individually
or given as a class of molecules (12).
Steroids, although being the main cause of drug-
induced hyperglycemia (13), have not been specifically
reported to induce DKA in T2DM. However, a retrospec-
tive study by Jabbar et al (4) has mentioned 1 case of
steroid-induced DKA in a study population with T2DM.
Our patient received prednisone, which is classified as
an intermediate-potency glucocorticoid, with peak of
action occurring 4 to 6 hours after administration. When
administered in a single dose in the morning, it causes
glucose elevation predominantly in the evening and night,
without much effect on fasting glucose 24 hours after.
However, multiple, divided doses can cause persistent
hyperglycemia (14).
Steroids can induce hyperglycemia through multiple
mechanisms. For example, steroids can interfere with
signaling cascades (mainly involving glucose transporter
type 4) in muscle cells, leading to a reduction in insulin-
mediated glucose uptake and glycogen synthesis (15,16).
Steroids can also induce lipolysis and proteolysis, enhance
the effects of counterregulatory hormones such as gluca-
gon and epinephrine, and also induce insulin resistance
via the nuclear peroxisome proliferator-activated recep-
tor (13,16). In response to insulin resistance, usually there
is increased insulin secretion by pancreatic beta cells to
maintain glucose homeostasis, but at times this increase is
insufficient to compensate for insulin resistance resulting
in hyperglycemia (13,16,17).
Taken together these observations suggest steroids can
cause hyperinsulinism in a state of insulin resistance. In
non-diabetic subjects, this effect is compensated for by an
increase in endogenous insulin secretion, thereby prevent-
Copyright © 2018 AACE Steroid-Induced DKA, AACE Clinical Case Rep. 2018;4(No. 2) e133
ing hyperglycemia (17,18). However, in patients with
T2DM, who may already have insulin resistance and low
insulin production, this compensation may be inadequate
to offset the metabolic effects of steroids (13,17). These
effects result in hyperglycemia and, in extreme settings
like in our case, the antilipolytic effect of insulin is lost,
resulting in DKA. Although DKA in patients with T2DM
tends to have less severe acidosis (18,19), our patient had
severe acidosis. Our patient also had a high insulin require-
ment, which may not be unusual for DKA in T2DM, as
patients may require larger amounts of insulin to correct
hyperglycemia (20).
Of consequence, it has been reported that
DKA-associated 30-day mortality is higher in T2DM than
in type 1 diabetes mellitus (11.9% versus 2.4%, respective-
ly) (21). On a more positive note, other studies have shown
that about 50 to 66% of patients with T2DM who were
admitted to the hospital due to DKA and required insu-
lin on discharge, were able to stop insulin at some point
(4,20,22). This may reflect recovery of beta cell function
after resolution of the acute hyperglycemic episode (gluco-
toxicity). Therefore, need for continuation of insulin should
be assessed in such individuals at each follow-up visit.
CONCLUSION
We presented a case report of DKA precipitated by
steroid use in T2DM which to our knowledge has not
been previously reported as the sole cause. Patients with
T2DM who receive glucocorticoids should be monitored
carefully, as steroids can precipitate DKA, in the absence
of any other triggering factor, even in patients with well-
controlled T2DM.
DISCLOSURE
The authors have no multiplicity of interest to disclose.
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