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Corticosteroid medications and
diabetes mellitus
Trisha DunningRN MEd FRCNA, Clinical Nurse Consultant- Diabetes Education,
Departmentof Endocrinologyand Diabetes, St Vincent’s Hospital,
41 Victoria Parade, Fitzroy, Victoria 3065, Australia
Introduction
The corticosteroids or adrenocortical
steroid hormones are steroid molecules
released by the adrenal cortex under the
control of the pituitary hormone corti-
cotrophin (ACTH). They are classified as
having predominantly glucocorticoid,
mineralcorticoid, androgenic or oestro-
genic effects’. The glucocorticoids are of
major interest with respect to their effects
on blood glucose, precipitating ‘steroid-
induced’ diabetes or hyperglycaemia in
established diabetes.
Glucocorticoids influence the function
of most body cells. They inhibit corti-
cotrophin secretion from the pituitary,
decrease insulin release from the beta
cells and impede glucose utilisation in
muscle. In particular,glucocorticoids lead
to insulin resistance which may be a result
of effects on intracellular pathways, de-
creased glucose transport, or increased/
decreased effects on insulin binding to its
receptors*. Glucocorticoids are known to
stimulate gluconeogenesis and glycogen
synthesis leading to increased hepatic
glucose output and decreased utilisation
of amino acids in muscle and fat. They
also have a role in the oxidation, syn-
thesis, and storage of fats. The gluco-
corticoid effects depend to some extent
on their duration of biological activity.
The diabetogenic effects may be tem-
porary if a specific course of steroids is
required, but may recur if the dose is
increased or if steroid treatment is
required intermittently. Prolonged treat-
ment with steroids can unmask latent
diabetes or aggravate pre-existing dia-
betes3.
Prescribing glucocorticoid
medications
Glucocorticoidmedications are important
treatment options and are prescribed in
the following instances:
1. To control specific disease processes
such as inflammatory conditions, hae-
matologic malignancy, allergic react-
ions and shock where they can be used
intermittently to control exacerbations
of the disease or at a low maintenance
Prudical Didwtes Itrfmwtional Novemher/Ih.cemher 1936 Vol. 13 No. 6
REVIEW ARTICLE
dose with the dose being increased ministration of oral glucocorticoids is
during disease exacerbations. associated with clinically important side-
2. As long-term hormone replacement effects which are dose-related, shown in
therapy following some endocrine Figure 1 (bullet points 3 & 4). The side-
diseases/surgery such as pituitary effects can be minimised by careful
tumours. choice of the steroid and alternate-day or
interrupted-dose regimens. Medications,
The advantages of using steroids over even in high doses, given for less than one
other treatment must be considered care- week usually d o not result in side-effects,
fully before commencing a course of although glucose intolerance can occur
steroids. The decision to use steroids will within 48 hours of the commencement of
depend on: glucocorticoids.
0 The severity of the presenting disease Intravenous administration of corticos-
and the individual’s response to other teroids tends to produce a shorter dura-
treatment measures, eg physiotherapy tion of action compared with oral ad-
and pain relief for arthritis. ministration and does not usually cause
How long steroid therapy will be very high blood glucose levels if only one
required (acute short-termtreatment o r or two doses are given. Figure 2 depicts
long-term) the duration of biOlOgiCd1 action of some
Presence of risk factors for side-effects of the commonly prescribed gluco-
(the elderly, children, existing glucose corticoid medicationsd. In practice, the
intolerance, diabetes or previous gesta- biological action of a given steroid will
tional diabetes, hypertension, cardiac depend on its frequency of admini-
disease, psychosis). stration, the dose given, and the response
of the individual to the drug. In addition,
Cost of the particular corticosteroid.
mineralocorticoid versus glucocorticoid
The long-term, continuous, daily ad- action of particular steroids vary and may
Figute 7. Adverse effects of glucocorticoidmedications
0 Hypertension (occurs in 80%)
0 Osteoporosis resulting in fractures (particularly in post-menopausalwomen)
0 Impairedglucosetolerance and diabetes
0 Suppression of immunefunction leadingto opportunisticinfections
0 Poor wound healing with suppression of fibroblast activity
0 Changed behaviour and severe psychologicaldisturbances,predominantly euphoria
and depression
0 Muscle wasting and central obesity
0 Electrolyte disturbancessuch as hypokalaemia
0 Suppression of growth in children
0 Suppression of human pituitaryadrenal axis
Flgure 2. Duration of biological action of commonly prescribed glucocorticoidpreparations
Short-acting Intermediate Long-acting
Cortisol Prednisone Paramethasone
Cortisone Prednisolone Betamethasone
Methylprednisolone Dexamethasone
Triamcinolone
I
1%

Corticosteroid medications and diabetes mellitus
influence the side-effect profile of a par-
ticular individual.
There is some evidence that deflazocort
has a lesser tendency to produce osteo-
porosis and growth suppression, and has
fewer metabolic effects compared with
other commonly prescribed drugs such as
prednisolones7. Therefore deflazocort
appears to be the preferred drug in
people with diabetes, the elderly and
children, given the known potential to
cause complications. However, deflazo-
cort is not yet widely available outside the
United Kingdom, Germany, Italy, Spain
and Switzerland.
Close monitoring of people, particu-
larly those on high-dose coricosteroids, is
essential to detect and manage early any
side-effects, including diabetes. The opti-
mal delivery technique should be utilised
with the lowest effective dose admini-
stered for the shortest possible time.
Steroid medications must be withdrawn
gradually over many weeks after pro-
longed use, and pituitary/adrenal activity
closely monitored to determine the return
to normal activity which may take 6-15
months4. Prolonged steroid medication
also suppresses the normal immune
response to illness; sudden withdrawal
can predispose the patient to serious
infections.
Diabetogenic effects of
steroids
Glucocorticoid medications induce in-
creased hepatic output of glucose and
also insulin resistance, which may lead to:
Steroid-induced glucose intolerance
and frank diabetes mellitus.
0 Deterioration of blood glucose control
in people with established diabetes.
The degree of glucose intolerance and
insulin resistance depends on the specific
steroid used, the time and dose given and
the route of administ~dtion3.~. Individual
responses are very variable and it is
difficult to predict the impact of steroid
therapy on individual patient require-
ments for insulin or oral hypoglycaemic
agents (OHAS). People who have a family
history of diabetes or previous gestational
diabetes appear to be more likely to
develop diabetes when taking corticos-
teroid medications.
Management of diabetic
patients requiring steroid
medication
Physical and educational assessment to
establish diabetes knowledge and self-
care potential is essential. The blood
glucose should be monitored before each
187
REVIEW ARTICLE
meal and at bedtime for 2 6 4 8 hours, to
establish the blood glucose profile and
determine if insulin/OHAsare required o r
dose increases are needed, depending on
current management. The monitoring
regimen should be reviewed once the
need for, and the dose of, diabetic medi-
cations has been established, depending
on the individual patient response to
treatment.
The urine should be monitored for
ketones if the blood glucose remains
elevated. Steroid medications can induce
lipolysis and ketogenesis - the con-
ditions for ketone body formation which
carry the potential for diabetic keto-
acidosis.
Diabetic medication should be adjusted
according to the blood glucose profile
and the time of administration and dose of
the steroid medication. For example, if
the blood glucose level rises in the later
afternoon (which is often the case)
OHAs/insulin may be required before
lunch, or before teddinner. If the steroids
are needed on a temporary basis the
diabetic medication dose will usually de-
crease as the steroid therapy is decreased.
It is important to continue to monitor the
blood glucose during the steroid-weaning
process to detect hypoglycaemia or per-
sisting hyperglycaemia.
Alternate-day corticosteroid medication
regimens may produce greater effects on
blood glucose levels on the steroid day
than on the alternate d a v . Therefore
allowance must be made when pres-
cribing diabetic medication doses. Two
separate regimens may be needed -one
for the steroid day and one for the
alternate day. Alternate-day regimens are
recommended if steroids are required in
the long-term, especially for children.
Patients treated with OHAs on a low
stable dose of steroids may achieve
acceptable diabetes control; however,
insulin may be needed if steroids are
increased during illness or infection. If the
patient requires insulin therapy while on
steroid medications the need for con-
tinuing with insulin should be assessed
when steroids are no longer required or
are required intermittently. This can be
achieved by a trial without insulin, and
blood glucose monitoring.
The potential for intercurrent infection,
especially if the diabetes is poorly con-
trolled, should be considered. Corticos-
teroids can mask some of the signs and
symptoms of infection and lead to de-
creased resistance to infection and de-
layed wound healing. Extra blood glu-
cose monitoring will be necessary during
illness, often every two hours.
Pructical Diubetes Intenzutioiial NovernberDecember 1996 Vol. 13 No. 6
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People requiring permanent steroid
therapy will usually require increased
steroid doses during illness and surgery,
when doses of insulin/OHAs may also
need to be increased. It is standard prac-
tice to increase steroid doses during
illness because the patient’s own human
pituitary adrenal axis is suppressed by the
administration of steroid medications
(endogenous steroid production). The
steroid cover must be adequate but the
dual effects of the steroids and the illness
itself in increasing blood glucose must be
considered, and the minimum possible
increase in steroid dose used.
Injection sites should be inspected
regularly.
Children with poorly controlled dia-
betes and long-term steroid medications
have two poential modulators of growth
(diabetes and steroids). The potential for
suppressed growth must be considered
and every effort made to control both the
diabetes and the need for steroid@.
If behavioural changes occur as a con-
sequence of steroid therapy the potential
for self-care should be reassessed.
Management of non-
diabetic patients on steroid
medication
Hyperglycaemia may be transient while
the patient is on steroid medications.
However, the occurrence of hypergly-
caemia identifies the patient as being at
risk of developing hyperglycaemia again
under stress conditions (re-introduction
of steroids, infection). A family history of
diabetes or previous gestational diabetes
may mean that the patient is at increased
risk of developing steroid-induced dia-
betes.
The urine should be tested for glucose
daily, alternating the time of testing while
on steroids, particularly if there is a family
history of diabetes. If glycosuria de-
velops, the blood glucose should be
monitored for 24-48 hours (as for people
with diabetes) to ascertain the blood glu-
cose profile, then the testing frequency
should be reviewed. In addition, the urine
should be tested for ketones if glycosuria
OCCUTS.
The decision to commence OHAs/in-
sulin is based on persistent hypergly-
caemia and evidence that the metablic
disturbance is adversely affecting the
patient (development of hyperglycaemic
symptoms). I
The long-term significance of hyper-
glycaemia for those patients who develop
diabetes while on a course of corti-
costeroids which resolves on completion
of the course, and the potential for

Corticosteroidmedications and diabetes mellitus
developing diabetes later in life, has not
been established. Those with a family
history of diabetes who are also obese
may be at increased risk.
Patient education
The patient with steroid-induced diabetes
will need education about the manage-
ment of the primary disease as well as
diabetes educationlo.
Diabetes education can assist the
patient in preventing illness and hospitali-
sation due to the consequences of hyper-
glycaemia. The person with diabetes on
steroid medication who develops an in-
tercurrent illness requires early appro-
priate treatment.
Education should include advice about
blood and urine glucose testing and
Dates for your diary
2629 JANUARY 1997
4th Asian ISPAD Symposiumon Paediatric and
Adolescent DiabetesMellim. Bangkok, Thailand.
Details: Chanika Tuchinda, Faculty of Medicine,
Paediatrics, Siriraj Hospital, Mahidol University,
Bangkok 10700. Thailand. Tel: +66-2-411-3010 Fax:
+66-2-411-1371,
30 JANUARY 1397
Putting Goad Ideas Into Practice, Birmingham,
UK. A joint Practical Diabeles InlernationaVBDA
ECSConference. Details:'(see helow).
4 7 FEBRUARY 1997
Cardlovascular Disease Prevention m, Ken-
sington Town Hall, London. Delails: Hampton Medi-
cal Conferences Ltd, Hofer House, 185 Uxhridge
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(0)181783 0810 Fax: 4 4 (0)1817830292.
26 FEBRUARY 1997
F'overty and Health. Joint RCGP/RCN/ FPHM/
BMJ/RCP Conference, The Royal College o f Physic-
ians, London. llelails: RCGP, Courses and Con-
ferences IJnit, 14 Princes Gate, Hyde Park London
SW7 1PU.Tel: 0171 823 9703 Fax: 0171 225 3047.
10-11 APRIL 1997
British Diabetic Association Medical and Scien-
tific Section Spring Meeting, Harrogate Inter-
national Centre. Derails:Conference Office, BDA, 10
Queen Anne Street, London W1M OBD Tel: 0171 323
1531 Fax: 0171 6363096.
10-12 APRIL 1997
Molecular and Cell Biology of Type 2 Diabetes
and its Complications, Turin, Italy. Details: M
I'orta/ S Iannello. Dept Internal Med 1Jnivcrsity of
Turin, Corso AM Dogliotti 14, 10126 Turin, Italy. Tel:
+39.11.6632354Fax: +39.11.6634751.
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National Diabetes Congress, Marmaris. Turkey.
Details: Turkish Diabetes Association, Cekal Oker
sokak No. 10, Hdrhiye, 80230 Istanbul, Turkey. Fax:
+90.212.5306891or +90.212.2485523.
Pructicul Diabetes Internutionul Novernber/Lkcernber 19%
REVIEW ARTICLE
appropriate diet, based on individual
dietary requirements.
People should carry cards indicating
that they are on steroid treatment. The
cards should indicate the actions to take
during illness and provide details of the
name of the drug, dosage, and the
duration of treatment.
Acknowledgements
I am grateful to Nicole Hayes for typing
the manuscript and Dr Frank Alford for his
helpful comments.
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Pancreatic Beta Cell and Islet Research:
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16th International Congress of Nutrition, Mon-
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Prague 2, Czech Republic. Tel: +42-2-297271,296889
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Sixth Intematlonal Congress on Pancreas and
Islet Transplantation, International Biomedical
Science Park, San Raffaele,Milan. DetaiLF:Organising
Secretariat, Congress Centre, San Raffaele, Via Olget-
tina 58,20132 Milan.
8-10 OCTOBER 1997
British Diabetic Assodation Education and Care
Section Annual Conference, and Medical and
Scientific Section Autumn Meeting, Bournemouth
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10 Queen Anne Street, London W1M OBD Tel: 0171
323 1531 Fax: 0171 636 3096.
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ductions Ltd. Northumberland House, 11The Pavement,
Popes Lane, London W5 4NG, UK. Tel: +44 (0)181 566
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188