Many medications can cause drug-induced diabetes by increasing insulin resistance or affecting insulin secretion. Widely used medications like thiazide diuretics, beta-blockers, and statins weakly increase diabetes risk, while steroids, antipsychotics, immunosuppressants, protease inhibitors confer a high risk. Diabetes induced by medications may not always be permanent and blood glucose levels could return to normal after stopping the medication, but lifestyle changes are often needed to manage drug-induced diabetes.

1. Drug Induced Diabetes
By
Zeeshan Naseer

2. Drug Induced Diabetes
• A number of medications have side effects which include the raising
of blood glucose levels. Drug induced diabetes is when use of a
specific medication has lead to the development of diabetes.
• Many therapeutic agents can predispose to or precipitate diabetes,
especially when pre-existing risk factors are present, and these may
cause glucose control to deteriorate if administered to those with
existing diabetes.

3. Drug Induced Diabetes
• They may act by increasing insulin resistance, by affecting the
secretion of insulin, or both.
• For convenience, these agents may be subdivided into widely used
medications that are weakly diabetogenic, and drugs used for special
indications that are more strongly diabetogenic.

4. Drug Induced Diabetes
• Examples of the former include antihypertensive agents and statins,
• Examples of the latter include steroids, antipsychotics and a range of
immunosuppressive agents.
• There are also a number of known beta cell poisons including the
insecticide Vacor, alloxan and streptozotocin.

5. Thiazides
• Thiazide diuretics revolutionized the treatment of hypertension in the
1960s, but were soon noted to increase the risk of diabetes.
• Subsequent experience showed that that this risk is greatly reduced by
low-dose therapy, whose benefits therefore outweigh its risks.
• The thiazides have a weak inhibitory effect upon release of insulin
from the beta cell.
• This effect is so marked in one member of the family, diazoxide, that
this is used to control excessive insulin secretion by unresectable
insulinomas.

6. Beta-blockers
• These impair insulin release, especially agents that are not selective
for the β1-receptor subtype.
• Several studies have linked chronic use of β-blockers with an
increased risk for the development of diabetes.
• The Atherosclerosis Risk in Communities (ARIC) study found that
the risk of diabetes in was increased by 28% in those taking a beta-
blocker for hypertension over a 6-year period, as compared with other
medications. The risk conferred by non-selective beta blockers may be
enhanced if these are combined with a thiazide diuretic.

7. Statins
• Meta-analysis has shown an excess risk of ~9% of progression to
diabetes in those taking statins.
• A more recent comparison of high-dose versus moderate dose statin
therapy showed that statin use was associated with an increased risk of
diabetes equivalent to 2 cases per 1000 patient/yrs treated, but resulted
in 6.5 fewer cardovascular events per 1000 patient/yrs.

8. Drugs conferring a high risk of diabetes

9. Steroids
• Steroid drugs can induce a form of iatrogenic Cushing's syndrome, and
are probably the most widely used drugs which confer a high risk of
diabetes.
• A Canadian paediatric study found that 0.4% of childhood diabetes
was ascribed to medication, and 55 of 56 children in this category
were on steroids. Monogenic* diabetes was diagnosed in only 0.2% of
children.
• Anabolic steroids (synthetic androgens mimicking testosterone or
dihydrotestosterone) should not be confused with glucocorticoids.
Although they have many unwanted effects, diabetes is not among
them.
• * Different types of monogenic diabetes include neonatal diabetes and MODY (maturity onset
diabetes of the young).

10. Antipsychotic agents
• Antipsychotics may be used to treat schizophrenia and
symptoms of psychosis which may occur in people with
dementia.
• Side effects of antipsychotics include weight gain and
hyperglycemia (high blood glucose levels). Blood sugar
levels may return to normal if medication is stopped.

11. Antipsychotic agents
• However, if significant weight has been gained over the
course of the treatment. Insulin resistance and type 2 diabetes
may be permanent.
• Diabetes is, for example, considered to be 2-3 times as
common in people with schizophrenia as in the background
population, probably because of lifestyle factors such as
obesity and lack of exercise, although a family history of
diabetes is common in those with schizophrenia.

12. Immunosuppressive Agents
• A number of immunosuppressive agents affect β-cell growth,
proliferation and function.
• The most potent of these are the calcineurin inhibitors, which also
affect the nuclear factor of activated T-cells (NFAT) pathway;
examples are tacrolimus and ciclosporin A.
• This limits the application of these agents in the prevention of type 1
diabetes, and helps explain the high prevalence of post-transplantation
diabetes, observed in 13.4% of patients following solid-organ
transplantation (16.6% for tacrolimus vs 9.8% for ciclosporin)

13. Protease Inhibitors
• Protease inhibitors such as ritonavir form an important element in
highly active antiretroviral therapy (HAART) and strongly predispose
to the development of diabetes by increasing insulin resistance and
possibly by other direct effects upon the β-cell.

14. Other Agents
• Pentamidine, used by iv injection for the treatment of _Pneumocystis
carinii _pneumonia, can cause transient hyperinsulinaemia associated
with hypoglycaemia, followed by persistent beta cell failure requiring
insulin treatment.
• Nicotinic acid, used as a lipid-lowering agent, can induce diabetes
secondary to increased insulin resistance.

16. Is diabetes permanent?
• Diabetes may not be permanent but this can depend on other health
factors.
• With some medications, blood glucose levels may return back to
normal once the medication is stopped but, in some cases, the
development of diabetes may be permanent.

17. Managing drug induced diabetes
• If you need to continue taking the medication that has brought on
diabetes, it may make your diabetes more difficult to control than
would otherwise be the case.
• If you are able to stop the course of medication, you may find your
blood glucose levels become slightly easier to manage.
• Following a healthy diet and meeting the recommended exercise
guidelines will help to improve your chances of managing your blood
glucose levels.

18. References
• http://www.diabetes.co.uk/drug-induced-diabetes.html
• http://www.diapedia.org/other-types-of-diabetes-mellitus/drug-
induced-diabetes
• www.intechopen.com