title: mTOR inhibitors and diabetes.
abstract: The mammalian target of rapamycin (mTOR) inhibitors are drugs, primarily used as immunosuppressors that are now frequently used as antineoplastic therapies in various cancers (such as advanced renal cell carcinoma, advanced breast cancer, progressive pancreatic neuroendocrine tumors). They act on mTOR signaling pathway which plays a key role in regulating cell growth as well as lipid and glucose metabolism. Treatment with mTOR inhibitors is associated with a high incidence of hyperglycemia and new-onset diabetes, ranging from 13% to 50% in the clinical trials in which they have been used as anticancer therapies. The rate of severe hyperglycemia is also increased, ranging from 4 to 12% in the main phase III clinical trials. Due to limited human studies, the pathophysiology of mTOR inhibitor-induced hyperglycemia has not yet been totally clarified. However, data from animal studies suggest that the mechanisms responsible for hyperglycemia with mTOR inhibitors are likely due to the combination of impaired insulin secretion and insulin resistance. Due to the high rate of hyperglycemia associated with the use of mTOR inhibitors, a close and personalized follow-up of blood glucose is recommended in all patients.
authors.affiliation: Endocrinology-Diabetology Department, University-Hospital, and, Medicine University, Dijon, France; INSERM CRI 866, Medicine University, Dijon, France; Faculté de Médecine, Université de Nantes, Nantes, France. Electronic address: bruno.verges@chu-dijon.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.affiliation: INSERM CRI 866, Medicine University, Dijon, France; Clinique d'Endocrinologie, l'institut du thorax, CHU de Nantes, Nantes, France; INSERM, UMR1087, l'institut du thorax, Nantes, France; Faculté de Médecine, Université de Nantes, Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cariou
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D001786:Blood Glucose; D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases
keywords: Cancer; Diabetes; Everolimus; Hyperglycemia; Temsirolimus; mTOR inhibitors