Drug Induced Diabetes

By

Zeeshan Naseer

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.

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.

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.

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 unresectableinsulinomas.

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.

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.

Drugs conferring a high risk of diabetes

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).

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.

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.

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)

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.

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.

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.

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.

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