C A S E S T U D I E S

Case Study: Atypical Myocardial Infarction in a Man

With Type 2 Diabetes
Craig D. Wittlesey, MD
Presentation
F.E., a 54-year-old man with a history of
type 2 diabetes, hypertension, and Reit-
ers syndrome with prior hospitalizations
for pneumonia and sepsis presented to
the hospital emergency room complain-
ing of chest pain, weakness, and fatigue.
His chest pain was pleuritic in nature,
worsening with movement and deep
breathing. When he was motionless, the
pain completely resolved.
F.E.s electrocardiogram showed Q
waves in leads II, III, and aVF, a new
right bundle branch block, and mild ST
segment elevation in leads V4 through
V6. An urgent echocardiogram was
ordered to differentiate between peri-
carditis and ischemia. The echocardio-
gram showed marked motion abnormali-
ties in the inferior posterior, lateral wall.
An initial troponin I was 238 ng/ml (nor-
mal range 02.5 ng/ml).
The patient was taken for emergent
cardiac catheterization. This demonstrat-
ed an occluded right coronary artery that
was opened with primary angioplasty
and stent placement.
Questions
1. Is silent ischemia or atypical presen-
tation of myocardial ischemia more
common in diabetes?
2. What other disease states may pre-
dispose to the development of atypi-
cal chest pain syndromes?
3. What is the proposed mechanism for
atypical or silent ischemia in dia-
betes?
4. Which patients with diabetes should
undergo myocardial assessment?
Commentary
Manifestations of coronary artery dis-
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CLINICAL DIABETESVolume 20, Number 2, 2002
ease (CAD) include overt, typical chest
pain syndromes, atypical symptomatic
ischemia, and asymptomatic or unno-
ticed ischemia. Previously unrecognized
CAD may become apparent with abnor-
malities on a resting electrocardiogram
including electrocardiographic left ven-
tricular hypertrophy, nonspecific ST and
T wave abnormalities, Q waves and
interventricular conduction delays
including bundle branch block. Silent
CAD may also be recognized during an
asymptomatic positive stress test.
For several years, it has been postu-
lated that people with diabetes have a
higher prevalence of asymptomatic or
atypical CAD. The literature is far from
clear on this point. What appears undeni-
able is that diabetes is an independent
risk factor for the development of early
CAD. In addition, the diagnosis of type
2 diabetes carries with it an increased
risk of abnormal lipid profiles and
hypertension (Syndrome X), both of
which are independent risk factors for
CAD. People with type 1 diabetes often
lack other associated risk factors for ath-
erosclerosis. Duration of diabetes seems
to be the predominant predictor of CAD
in these patients.
Silent myocardial ischemia was
examined in the Framingham study.
1
In
this cohort of 5,209 men and women,
unrecognized anterior and inferior
myocardial infarctions (MIs) were estab-
lished by comparing biennial electrocar-
diograms.
More than 25% of all MIs in the
Framingham cohort were discovered ret-
rospectively, only after clear evidence of
myocardial damage was noted on these
routine electrocardiograms. Of these
unrecognized MIs, 48% in men and 46%
in women were actually silent. The
remaining unrecognized MIs were so
atypical that neither the patient nor the
attending physician entertained MI as a
possible diagnosis.
Women had a higher incidence of
unrecognized infarction than men (35 vs.
28%) at all age levels. Hypertension was
the only CAD risk factor, in both men
and women, that was statistically corre-
lated with unrecognized MI. This was a
consistent finding even after excluding
those patients with coexisting diabetes.
In the cohort with diabetes, MI was
unrecognized in 39% of men, a clear
excess. In women, only 17% of the MIs
were unrecognized, less than half the
rate noted in the nondiabetic population.
The authors offered no theory for these
divergent findings.
Other studies have demonstrated an
increased incidence of unrecognized
CAD in patients with diabetes. In a case-
control study, 41 of 132 patients with
diabetes and 42 of 140 control subjects
matched for age, sex, and risk factors
other than diabetes, were noted to have
electrocardiographic stress test evidence
of myocardial ischemia.
2
To rule out
possible false-positive stress tests, 36 of
the 41 patients with diabetes and 34 of
42 control patients underwent coronary
angiography. This demonstrated signifi-
cant coronary narrowing in 39% of those
with diabetes and in only 18% of the
control subjects (P < 0.05). Other studies
have demonstrated similar correlations
between diabetes and silent or atypical
ischemia.
Autonomic and sensory dysfunction
have been postulated as possible mech-
anisms for unrecognized ischemia in
patients with diabetes. A case-control
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diabetes to a higher incidence of
atypical or silent myocardial
ischemia.
3. Autonomic dysfunction may in part
explain altered anginal perception in
diabetes.
4. The American Diabetes Association
1998 consensus statement on
Diagnosis of Coronary Heart Disease
in People With Diabetes
4
recom-
mended the following indications for
cardiac stress testing:
A. Typical or atypical cardiac symp-
toms
B. Resting electrocardiograph sug-
gestive of ischemia or infarction
C. Peripheral or carotid occlusive
arterial disease
D. Sedentary lifestyle, age >35 years,
and plans to begin a vigorous
exercise program
E. Two or more of the risk factors
listed below in addition to dia-
betes
1. Total cholesterol >240 mg/dl,
LDL cholesterol >160 mg/dl, or
HDL cholesterol <35 mg/dl
C A S E S T U D I E S
study involving 32 diabetic patients and
36 control subjects, all with typical
anginal symptoms, tested this hypothe-
sis by studying the anginal perceptual
threshold, defined as the time from
onset of 0.1 mV ST segment depression
to the onset of anginal symptoms dur-
ing treadmill stress testing.
3
The results
indicated that the perception of angina
was significantly (P < 0.001) delayed
in patients with diabetes compared to
the control group, despite the fact that
ST segment depression occurred earlier
in the diabetic group. Further studies on
patients with diabetes demonstrated
significant autonomic dysfunction in
the heart rate response to Valsalva and
deep breathing, which were directly
correlated with increased anginal per-
ceptual threshold.
Clinical Pearls
1. Atypical or silent presentations of
CAD may be more frequent in
patients with diabetes.
2. Comorbid states such as hyperten-
sion may predispose patients with
Volume 20, Number 2, 2002CLINICAL DIABETES
102
2. Blood pressure >140/90 mmHg
3. Smoking
4. Family history of premature
CAD
5. Positive micro/macroalbumin-
uria test
REFERENCES
1
Kannel WB: Silent myocardial ischemia and
infarction: insights from the Framingham Study.
Cardiol Clin 4:583591, 1986
2
Naka M, Hiramatsu K, Aizawa T, Momose
A, Yoshizawa K, Shigematsu S, Ishihara F, Niwa
A, Yamada T: Silent myocardial ischemia in
patients with non-insulin-dependent diabetes mel-
litus as judged by treadmill exercise testing and
coronary angiography. Am Heart J 123:4653,
1992
3
Gamini A, Kopelman P, Ingram D, Swash M,
Mills P, Timmis A: Exertional myocardial
ischemia in diabetes. Am Coll Cardiol 15:7277,
1990
4
American Diabetes Association: Diagnosis
of coronary heart disease in people with diabetes
(Consensus Statement). Diabetes Care
21:15511559, 1998
Craig D. Wittlesey, MD, is co-director of
the Central Washington Providence Dia-
betes Care Center in Wapato, Wash.
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C A S E S T U D I E S
Case Study: Peripheral Neuropathy in Diabetes:
Is It Diabetic Neuropathy?
Dace L. Trence, MD, FACE
Presentation
T.T., a 26-year-old woman with type 1
diabetes diagnosed at the age of 14, pre-
sented with persistent burning pain in
her lower extremities and upper extremi-
ty digital paresthesias that made her
work as a dental hygienist difficult.
Recently, her family had noted that she
seemed to be stumbling at times. She
reported that neither increased doses of
a selective serotonin reuptake inhibitor
(SSRI) nor trials of tricyclic antidepres-
sants (phenytoin [Dilantin], carba-
mazepine [Epitol, Tegretol], or
gabapentin [Neurontin]) had relieved her
symptoms.
T.T. had no known history of diabet-
ic retinopathy or nephropathy. She also
denied resting tachycardia, orthostatic
lightheadedness, early satiety, early
morning nausea, changes in bowel
habits, or postprandial sweating. She did
note a history of depression, which was
treated with counseling and medication.
She also noted menstrual irregularity,
dysmenorrhea, and premenstrual emo-
tional lability. She had been treated with
oral contraceptives in the past, but had
discontinued these 68 months ago.
Her glycemic control had never been
optimal despite a multiple-dose insulin
program. Her hemoglobin A
1c
(A1C)
levels had typically been in the 89%
range.
Exam revealed a moderately over-
weight (BMI 27 kg/m
2
) woman with a
blood pressure of 138/85 mmHg with no
orthostatic change and a resting pulse of
72 with no change with Valsalva maneu-
ver. Lower extremity exam showed nor-
mal skin pigmentation, easily palpable
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CLINICAL DIABETESVolume 20, Number 2, 2002
dorsalis pedis pulses, but decreased posi-
tion sense as well as decreased sensation
to 10-g monofilament testing.
Laboratory testing revealed an A1C
of 8.2% (normal <6.5%); an albumin-to-
creatinine ratio of 25 g/mg (normal
<30 g/mg); and normal serum creati-
nine, complete blood count, total protein,
sedimentation rate, and thyroid stimulat-
ing hormone.
When asked to bring in all over-the-
counter and prescribed medications pre-
viously and currently used, the patient
acknowledged taking pyridoxine (vita-
min B6), a medication that she had start-
ed after reading on the Internet that it
could help in the treatment of both pre-
menstrual syndrome and carpal tunnel
syndrome. She reported taking pyridox-
ine at a dosage of 200500 mg daily for
the past 6 months.
Questions
1. What is the differential diagnosis of
peripheral neuropathy in people with
diabetes?
2. What commonly used medications
can be associated with peripheral
neuropathy?
3. Are there any known benefits to the
use of pyridoxine in a person with
diabetes?
Discussion
Peripheral neuropathy has many poten-
tial etiologies yet is often quickly attrib-
uted to diabetes in diabetic patients, par-
ticularly in those with poorly controlled
diabetes. The differential diagnosis
includes metabolic etiologies, such as
uremia, myxedema, amyloidosis, and
deficiency of vitamin B12, B6, or thi-
amine; toxic etiologies, such as ethanol
or heavy metal exposure; and as a side
effect of prescribed medications, includ-
ing allopurinol (sold under various
brand names), isoniazid (INH, Lanizid,
Nydrazid), and nitrofurantoin
(Macrodantin, Macrobid).
Peripheral neuropathy may also be
associated with malignancy, such as
lymphoma or bronchogenic or gastric
carcinoma, and with infectious/inflam-
matory processes, such as monoclonal
paraproteinemias, HIV, lyme disease,
borreliosis, or leprosy. In addition, it
may also be associated with a variety of
familial syndromes, such as Charcoat-
Marie-Tooth syndrome.
1
Providers must also recognize that
over-the-counter remedies can have side
effects including, in this instance,
peripheral neuropathy. High-dose pyri-
doxine (B6) has been reported to cause
sensory dysfunction and ataxia that
improves after the vitamin is discontin-
ued. Although initially believed to be
related to mega-dose ingestion,
2
these
symptoms have been reported in lower-
dose users including those taking as little
as 200 mg/day.
3
Most patients note
improvement or complete resolution of
symptoms with discontinuation of pyri-
doxine. T.T. had substantial improve-
ment within just 23 weeks of discontin-
uing pyridoxine.
Although neuropathy is a common
complication of diabetes, it is important
to be aware of other potential etiologies
of neuropathy in diabetic patients to
avoid missing an important diagnostic
clue for a treatable condition. A careful
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2. A thorough history and appropriate
laboratory testing are needed to
ensure completeness of the search for
these etiologies. This should include
a review of all over-the-counter med-
ications being used about which
patients may not initially volunteer
information.
3. Several medications commonly used
by people with diabetes may be asso-
ciated with neuropathy.
4. Evidence of a beneficial role for pyri-
doxine in the treatment of neuropathy
is inconclusive.
REFERENCES
1
Eaton S, Tesfaye S: Clinical manifestations
and measurement of somatic neuropathy. Dia-
betes Rev 7:312325, 1999
2
Schaumburg H, Kaplan J, Windebank A,
Vick N, Rasmus S, Pleasure D, Brown M: Senso-
ry neuropathy from pyridoxine abuse: a new
megavitamin syndrome. N Engl J Med
309:445448, 1983
C A S E S T U D I E S
history should be obtained including use
of both over-the-counter and prescription
medications because commonly used
agents can be associated with neuropa-
thy.
46
Treatment of specific problems, such
as carpal tunnel syndrome, with pyridox-
ine has been thought at times to be bene-
ficial,
7
but not all data have supported
this.
8
Strongly encouraging patients to
bring in all their medications can be a
simple but helpful tool in making a more
accurate diagnosis and effective thera-
peutic intervention.
Clinical Pearls
1. The differential diagnosis of periph-
eral neuropathy in diabetic patients is
not limited to diabetes, but rather
may have a variety of metabolic,
toxic, inflammatory, malignant,
infectious, and familial causes.
Volume 20, Number 2, 2002CLINICAL DIABETES
104
3
Parry GJ, Bredesen DE: Sensory neuropathy
with low-dose pyridoxine. Neurology
35:14661468, 1985
4
Jeppesen U, Gaist D, Smith T, Sindrup SH:
Statins and peripheral neuropathy. Eur J Clin
Pharmacol 54:835838, 1999
5
Chakraborthy TK, Ruddell WS: Guillaine-
Barre neuropathy during treatment with captopril.
Postgrad Med J 63:221222, 1987
6
Boulton AJM: Current and emerging treat-
ments for the diabetic neuropathies. Diabetes Rev
7:379386, 1999
7
Folkers K, Ellis J: Successful therapy with
vitamin B6 and vitamin B2 of the carpal tunnel
syndrome and need for determination of the
RDAs for vitamins B6 and B2 for disease states.
Ann N Y Acad Sci 585:295301, 1990
8
Jacobson MD, Plancher KD, Kleinman WB:
Vitamin B6 (pyridoxine) therapy for carpal tunnel
syndrome. Hand Clin 12:253257, 1996
Dace L. Trence, MD, FACE, is associate
director of the Diabetes Care Center and
an assistant professor in the Division of
Nutrition, Endocrinology, and Metabo-
lism at the University of Washington
School of Medicine in Seattle.
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