Medication‐induced diabetes mellitus

Abstract

Epidemiological studies and case reports have demonstrated an increased rate of development of diabetes mellitus consequent to taking diverse types of medication. This review explores this evidence linking these medications and development of diabetes and presents postulated mechanisms by which the medications might cause diabetes. Some medications are associated with a reduction in insulin production, some with reduction in insulin sensitivity, and some appear to be associated with both reduction in insulin production and insulin sensitivity. Patients are often taking multiple medications and so it is hard to determine which medication was responsible for the side effect. For example, organ transplant patients may be taking a glucocorticoid and a calcineurin inhibitor, so an epidemiological study has difficulty ascribing the side effect to one or the other or the combination of these medications. There are also covariants such as the weight gain associated with steroids or antipsychotics making it difficult to know if development of diabetes was a primary or secondary effect of the medication. When we turn to deciphering the mechanism by which a medication caused diabetes, there are often multiple plausible molecular mechanisms identified in animal or in vitro studies, but these do not necessarily identify the clinically relevant mechanism(s) in humans. Finally, for pediatrics, there are few studies in children and data from adults can only be assumed to apply to children.A summary of the most common medications that have been associated with development of diabetes and their most plausible mechanism is presented in Table 1. | COMMON MEDICATIONS THAT DECREASE BOTH INSULIN SENSITIVITY AND INSULIN RELEASE | GlucocorticoidsGlucocorticoids are widely used medications and clinical experience indicates that diabetes is a frequent side effect. Ingle first reported glucosuria in rats receiving glucocorticoid.1 A human retrospective epidemiological study of adult Medicaid patients carried out over 9 years identified almost 12 000 persons with new onset diabetes and closely matched controls which did not develop diabetes.Patients who were taking glucocorticoid were more likely to be in the diabetes group (relative risk 2.23) and the relative risk was dose dependent. 2 One intuitive hypothesis for the mechanism by which glucocorticoids cause diabetes is development of insulin resistance.To test this hypothesis, hyperinsulinemic-euglycemic clamps with tritiated glucose tracer were performed on 10 healthy subjects ). In addition, there is evidence for decreased insulininduced vasodilation in muscle leading to reduced glucose delivery to

ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents

“…However, an OGTT is not needed and should not be performed if diabetes can be diagnosed using fasting, random, or postprandial criteria as excessive hyperglycemia can result (E) . Hyperglycemia detected under conditions of stress, such as acute infection, trauma, surgery, respiratory distress, circulatory, or other stress may be transitory and requires treatment but should not in itself be regarded as diagnostic of diabetes (E). The possibility of other types of diabetes should be considered in the child who has negative diabetes‐associated autoantibodies and (B) : an autosomal dominant family history of diabetes (maturity‐onset diabetes of the young [MODY]) age less than 12 months and especially in first 6 months of life (NDM [neonatal diabetes mellitus]) mild‐fasting hyperglycemia (5.5‐8.5 mmol [100‐150 mg/dL]), especially if young, non‐obese, and asymptomatic a prolonged honeymoon period over 1 year or an unusually low requirement for insulin of ≤0.5 U/kg/day after 1 year of diabetes associated conditions such as deafness, optic atrophy, or syndromic features (mitochondrial disease) a history of exposure to drugs known to be toxic to β‐cells or cause insulin resistance (eg, immunosuppressive drugs such as tacrolimus or cyclosporin; gluocorticoids or some antidepressants) The differentiation between type 1, type 2, monogenic, and other forms of diabetes has important implications for both treatment and education (E) .…”

“…The possibility of other types of diabetes should be considered in the child who has negative diabetes‐associated autoantibodies and (B) : an autosomal dominant family history of diabetes (maturity‐onset diabetes of the young [MODY]) age less than 12 months and especially in first 6 months of life (NDM [neonatal diabetes mellitus]) mild‐fasting hyperglycemia (5.5‐8.5 mmol [100‐150 mg/dL]), especially if young, non‐obese, and asymptomatic a prolonged honeymoon period over 1 year or an unusually low requirement for insulin of ≤0.5 U/kg/day after 1 year of diabetes associated conditions such as deafness, optic atrophy, or syndromic features (mitochondrial disease) a history of exposure to drugs known to be toxic to β‐cells or cause insulin resistance (eg, immunosuppressive drugs such as tacrolimus or cyclosporin; gluocorticoids or some antidepressants) …”

“…• a history of exposure to drugs known to be toxic to β-cells or cause insulin resistance (eg, immunosuppressive drugs such as tacrolimus or cyclosporin; gluocorticoids or some antidepressants). 1 • The differentiation between type 1, type 2, monogenic, and other forms of diabetes has important implications for both treatment and education (E). Diagnostic tools, which may assist in confirming the diabetes type if the diagnosis is unclear, include:…”

In vitro inhibition of human erythrocyte hexokinase by various hyperglycemic drugs

“…Drugs and chemicals that inhibit hexokinase enzyme and cause decrease in erythrocyte energy may reflect cumulative increased oxidative random destruction . Drug‐induced hyperglycemia occurs due to a variety of drugs and mechanisms .…”

“…Drugs and chemicals that inhibit hexokinase enzyme and cause decrease in erythrocyte energy may reflect cumulative increased oxidative random destruction. [7] Drug-induced hyperglycemia occurs due to a variety of drugs and mechanisms. [8][9][10][11] Mechanisms range from decreased insulin secretion to decreased insulin action to direct neurological effects.…”