mTOR and Cardiovascular Diseases: Diabetes Mellitus.

The mammalian targets of rapamycin (mTOR) inhibitors are potent immunosuppressors used for prevention of acute rejection following transplantation and have been more recently used as anticancer drugs. mTOR inhibitors have a significant impact on glucose metabolism and induce frequently diabetes. mTOR inhibitors, when used as immunosuppressive agents (sirolimus, everolimus), can induce diabetes with an incidence which is low when used without calcineurin inhibitors (CNI) but high when used in combination with CNI (from 11.0% to 38.1%). mTOR inhibitors used as anti-cancer agents (everolimus, temsirolimus) increase significantly the risk for new-onset diabetes and augment by 5 the risk for severe hyperglycemia. The deleterious effect of mTOR inhibitors on glucose metabolism is due to an increased insulin resistance secondary to a reduction of the insulin signaling pathway within the cell and to a reduction of insulin secretion via a direct effect on the pancreatic beta cells. Due to the risk for diabetes, it is recommended, when starting a treatment with an mTOR inhibitor, to check fasting blood glucose every 2 weeks during the first month of treatment then every month and HbA1c every 3 months and to intensify self-monitoring of blood glucose in patients with known diabetes. When fasting blood glucose is above 126 mg/dl (7.0 mmol/L), when plasma glucose is above 200 mg/dl at any time or when HbA1c is above 6.5%, it is recommended to start antidiabetic treatment. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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