Letters
amounts of glucose, reacting to concen-
trations as low as 0.05% (g/100 mb (2)
‘The intensity of color change crudely re-
fects the amount of glucose present, to a
maximum concentration of 2%, Placing a
rop of the beverage in question on a
strip of Tes-tape will rapidly reveal
whether it contains sugar. The only
known causes ofa false positive reaction
are the presence of chlorine from cleans-
ing agents or contamination with perox-
ide-containing detergents (3).
To gain some insight into the
magnitude of the problem for our pa-
tients, we conducted a survey of many
establishments that serve fountain
rinks, with an emphasis on fast-food
chains, the source of most complaints
from our patients. We tested 37 samples
of diet colas ordered at 23 different loca-
tions, mainly in central North Carolina,
‘over a period of several months. (Colas
‘were chosen for evaluation because these
are often the only beverages available in
fast-food restaurants) Because the nor-
mal reaction of Tes-tape to a diet cola is
completely negative, even a trace reac-
tion was considered a positive response
We expressed the data with the Mietti-
nen exact confidence limits (4). Sixteen
of 37 (43.2%) drinks tested positive for
lucose, with a 95% confidence interval
of 28.1% -59.4% (4). Of the 16 positive
responses, 5 samples showed a markedly
positive result of 2%.
There are several possible expla
nations for positive responses in our sur-
vey. We did not investigate the source or
sources of the error. However, we spec-
ulate that any of the following possible
events may have occurred. First, the
manufacturer may have incorrectly filled
the tanks. (It is important to note that
wwe have never found even a trace pos-
itive result in canned or bottled diet
soft drinks.) Second, the counter per-
son may have dispensed the wrong
beverage. Third, the tanks may have
been hooked up to the dispenser incor-
rectly. Finally, because positive read-
ings on the Tes-tape may also result
from the presence of certain cleansing
agents, we must also consider the pos-
sibility that contamination of the bev-
erage may have occurred if the dis-
penser was not cleaned properly
We were surprised by the magni-
tude of the positive findings in our sur-
vey. However, further anecdotal reports
from patients and colleagues lead us to
believe that our results are not atypical
To determine the extent of this problem
nationwide, investigation should be con-
ducted in different locations. The varia-
bles that might influence the positive re-
sponse rate must also be assessed.
References
1. Pennington JAT, Church HN: Bowes and
Church's Food Values of Portions Commonly
Used. L4th ed. New York, Harper & Row,
1985, p. 5
2. Feldman JM, Lebovitz FL: Tests for glyco-
suria: an analysis of factors that cause mis
leading results. Diabetes 22:115—21, 1973
3. Berger W: Test strip methods for estimat-
ing glycosuria: uses and possible errors
isch Med Wochenschr 98:2304—305,
1973
4. Mietinen OS: Comment, | Am Stat Assoc
69:380-82, 1974
Hypoglycemia Induced by
Enalapril in Patient With Insulin
Resistance and NIDDM
Daw S.H. Bett, up
logical cause of unexpected hypo-
glycemia in an insulin-using pa-
tient is usually found with an ad-
equate patient assessment. On rare
‘occasions, no rational explanation can be
found, Such a case is described in which,
despite long-standing diabetic neuropa-
thy, no previous severe hypoglycemia
hhad occurred and in which retrospec-
tively severe hypoglycemia was found
and proved to be caused by using an
angiotensin-converting enzyme (ACE)
inhibitor.
‘A 65-yr-old thin black man had
nnon-insulin-dependent diabetes mellitus
(NIDDM) for 19 yr and had been using
insulin for 18 yr. There was no history of
diabetic ketoacidosis or severe hypogly-
ceria. However, he had proliferative di-
abetic retinopathy for which he had laser
treatment, markedly symptomatic distal
symmetrical polyneuropathy, autonomic
neuropathy with impotence, limited
Fro THE DepasrMent OF MEDICINE, THE UNIVERSITY OF ALABAMA AT BiRaNGii, SCHOOL OF
Mepiane, Birinci, ALABAMA
[ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO DaMIb S.H. Bu, wo, 1808 7mm AVENUE
Sour, Univers Starion, Birwancitan, AL 35294
oa
Daseres Cane, voune 15, wunen 7, Juv 1992joint mobility of diabetes, and a history
of a cerebrovascular accident affecting
the left side of his body. Proteinuria had
recently been discovered. He had no ev-
idence of ischemic heart disease or pe-
ripheral vascular disease
His diabetes was always poorly
controlled. His HbA, levels over the pre-
vious 5 yr had ranged between 15 and
16% (normal range 5.0-8,5%). Because
he needed large doses of split-mixed in-
sulin (1.5 U/kg) to achieve this poor
control, it was likely that his poor control
‘was secondary to insulin resistance,
‘which had not been overcome with large
doses of purified pork or human insulin,
He had recently been discovered
to have 2+ proteinuria and hypertension
with a blood pressure of 160/90 mmHg
and because of this was started on 5
‘mg/day enalapril. On that visi, his HbA,
was 13.4%, and a postprandial glucose
‘was 283 mg/dl (15,7 mM). Because of his
ppoor glycemic control, his split-mixed
insulin regimen was increased to a total
of 130 U—an increase of 20%,
Two weeks after his last clinic
visit, his wife could not wake him for
breakfast. The paramedics were called
and he responded to 50 cc 50% dextrose
and water. He was subsequently seen in
the emergency room that day, and his
insulin dose was reduced by 20%, and
he was discharged home. Two days late,
oon the reduced dose of insulin, he was
unable to avoid chronic hypoglycemia,
despite home glucose monitoring and
taking extra calories. Because of this, he
was admitted to the hospital for further
evaluation and treatment.
In the hospital, he became well
controlled on a total insulin dose of 40
Uiday in a split-mixed regimen. After
discharge, his blood glucose again began
to drop, and he was finaly stabilized as
an outpatient on 18 U/day NPH. His
serum creatinine, cortisol, and thyroxine
‘were normal. We then realized that his
decreased insulin needs coincided with
the commencement of enalapril therapy.
To confirm that enalapril had reduced
his insulin resistance, the enalapril was
withdrawn, and his insulin dose was not
changed. At home, after 2 days, his
blood glucose began to rise and when
seen a5 an outpatient 1 wk later his fast
ing blood glucose had risen to 349 mg/
percent (19.45 mM). Enalapril was rein-
stated and his insulin dose was not
changed. After 2 days at home, his blood
glucose began co fall, and after 1 wk
when checked as an outpatient, his 2-h
postprandial blood glucose was 137
‘mg/dl (7.6 mM). The enalapril was con-
tinued and insulin dose was not
changed
Thus, in this case, enalapril
caused a decrease in insulin resistance
with a corresponding decrease in exoge-
nous insulin requirements, Within 2
days of withdrawal of enalapril, the in-
sulin resistance recurred with a corre-
sponding increase in serum glucose level
oon a fixed dose of insulin, Again, within
3 days after reinstitution of enalapril in-
sulin resistance decreased with a corre-
sponding decrease in serum glucose
Thus, with withdrawal of and rechalleng-
ing with enalapril, we confirmed that
enalapril decreased this patient's insulin
resistance,
‘ACE inhibitors are widely used to
treat hypertension in diabetic patients
‘Their choice is based on the lack of effect
‘on potency, peripheral vascular disease,
hyperlipidemia, and its protective effect
on the kidney. In addition, unlike
B-blockers, hypoglycemic symptoms are
not masked and hypoglycemia is usually
not induced (1). A further beneficial ef-
fect is a decrease in insulin resistance
‘with potential improvement in glycemic
control (2). However, the decrease in in-
sulin resistance could potentially lead to
hypoglycemia in the diabetic patient
treated with insulin or oral hypoglyce-
mics
Hypoglycemic episodes with cap-
topril have been described in three pa-
tients on insulin and two receiving a sul-
fonylurea G.4) and two people on a
combination of sulfonylureas and
biguanides (5). Enalapril-induced hypo-
‘glycemia in one patient on insulin and
cone patient on sulfonylurea have been
described (6). A mean decrease in fasting
glucose was also described with enalapril
in a comparative clinical trial involving
enalapril, hydrochlorothiazide, and
atenolol (7)
None of these studies have clearly
documented the effect of ACE inhibitors
con insulin requirements by withdrawing
the ACE inhibitor and rechallenging the
patient with this medication. In addition,
such a severe decrease in insulin resis-
tance with a corresponding decrease in
insulin needs has not been previously
described
Because ACE inhibitors decrease
insulin resistance by ~10% (2), itis sur-
prising that more cases of ACE inhibitor
induced hypoglycemia have not been de-
scribed, A possible reason for this is that
ACE inhibitors are commonly used in
combination with diuretics, which, by
increasing insulin resistance, neutralize
the effect of the ACE inhibitor. Similarly,
it ACE inhibitors are used with a
Be-blocker, a decrease in insulin resis-
tance will again be compensated for by
an increase in insulin resistance induced
by the B-blocker (8)
Thus, (0 the list of potential
causes of severe hypoglycemia in the pa-
tient with diabetes who requires insulin
ot oral sulfonylureas should be added
treatment with ACE inhibitors.
References
1. Bell DSH: Hypertension in the person
with diabetes. Am J Med Sci 297:228-32,
1989
2. Pollare T,Lithell H, Bere C: A compari-
son of the effects of hydrochlorothiazide
and captopril on glucose and lipid metab-
olism in patients with hypertension, N
Engl J Med 321:868-73, 1989
3, Fermiere M, Jachkar H, Richard JL, Bringer
J, Orsetti A, Miaouze J: Captopril and in-
‘sulin sensitivity. Ann Inter Med 102:134—
35, 1985,
4. Arauz-Puchecoc, Ramirez LC, Rios JM,
Raskin P: Hypoglycemia induced by angi=
‘rensin converting enzyme inhibitors in
patients with non-insulin-dependent dia-
Baseres Came, voune 15, nonmen 7, Jour 1997
3Letters
betes receiving sulfonylurea therapy. Am J
Med 89:811-13, 1990
5. Rett K, Wicklmayr M, Dietz GJ: Hypogly-
cemia in hypertensive diabetic patients
treated with sulfonylureas, biguanides and
‘captopril (Lewer). Lancet 319:1609, 1988
6. MeMurray J, Fraser DM: Captopril, enala-
pril and blood glucose (Lete). Lancet
1:1035, 1986
7, Helgeland A, Strommer R, Hagelund CH,
Treth $: Enalapril, atenolol and hydro
chlorothiazide in mild to moderate hyper-
tension: a comparative multi-center study
in general practice in Norway. Lancet
1872-75, 1986
8, Lithell HO, Pollare 7, Berne C: Insulin
sensitivity in newly detected hypertensive
patients: influence of Captopril and other
antihypertensive agents on insulin sensi-
tivity and related biological parameters. J
Cardiovasc Pharmacol 15:S46~52, 1990
Milk Allergy Masquerading as
Insulin Allergy
Daw S.H. Beu, 8
though with modem purified and
A hhuman insulins the incidence of
both local and systemic insulin al-
lergy is decreased, these Teactions stil
‘occur (1). Substances other than insulins
implicated as a cause of insulin allergy
include impurities in the alcohol used to
cleanse the injection site, protamine, and
zinc (1). A case is described in which the
allergy was caused by injected milk pro-
tein
‘An 18 yr-old previously healthy
white male showed the classic symptoms
of diabetes and was admitted to his local
hospital. His diabetes was controlled on
insulin and he received survival-skill
level diabetes education, During his hor
pitalization, he felt well and had no al-
lergic reactions to subcutaneously in-
jected insulin
‘Alter his discharge from the hos-
pital, his blood sugars rose dramatically
and did not decrease with extra subcu-
taneous injections. In addition, at the site
ot is “cloudy” insulin injections bur not
at his “clear injections,” he developed a
‘macular rash 2 h afier injection which
lasted 36 h. Because of these dificuties,
he sought help at our institution
After arriving at the diabetes
clinic his serum glucose was 453 mg/dl
He was asked to give 5 U of regular
row THe Scoot oF Mepicine, DeraRTMENT oF MeDicine, THE UNIVERSITY OF ALABAMA AT BiR-
INGHAM, BIRMINGHAM, ALABAMA,
[ADDRESS CORRESPONDENCE AND REPRINT REQUESTS TO DaMib S.H. BeuL, MB, 1808 7H AvENUE
Sour, Bresncins, AL 35294
insulin subcutaneously. On producing
his “insulins” it was discovered that he
‘was using two normal saline solutions;
one was clear and the other had a cloudy
appearance and obviously had been used
to practice mixing insulin, He had de-
cided not to purchase the human insulin
that had been prescribed until the “insu-
lins” that he had left the hospital with
hhad been used and he had thus been
injecting normal saline solutions. By con-
tacting the hospital where he had been
initiated on insulin 2 wk previously, it
‘was discovered that one vial of saline had
been made to resemble NPH insulin by
adding milk.
‘After treatment with split-mixed
regular and NPH human insulin, his di-
abetes was easily controlled and his skin
lesions disappeared within 36 h.
This case illustrates the need for
clear discharge instructions to the patient
with diabetes, especially those with a re-
cent onset of diabetes and initiation of
insulin therapy.
References
1, Galloway JA, deShazo RP: The clinical use
of insulin and the complications of insulin
therapy. In Diabetes Mellitus: Theory and
Practice. Ellenberg M, Rifkin H, Eds. 3rd
ced. Chaps. 25, New Hyde Park, NY, Med.
Exam, 1983, p. 519-38
336
Dasers Care, Voume 15, novmen 7, Ju 1992