The mechanism of glucocorticoid-induced diabetes mellitus is multifactorial. Glucocorticoids induce hepatic and extrahepatic insulin resistance, says Pankaj Shah, M.D., of the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at Mayo Clinic.
Glucocorticoid treatment impairs both glucose transport in fat and muscle cells and the ability of glucose to stimulate its own utilization (glucose effectiveness), as well as reducing glucose clearance. These agents have direct harmful effects on insulin-secreting beta cells of the pancreatic islets by inducing apoptosis. In addition, hyperglycemia induced by glucocorticoids is associated with reduced GLUT-2 expression and a decrease in glucose transport into the beta cells. Also, glucocorticoids can increase appetite and weight.
Glucocorticoid use is associated with increased concentrations of fasting and post-meal insulin and glucagon.
Dr. Shah notes, "As long as compensatory insulin release is adequate for the prevailing glucose concentration, hyperglycemia does not occur because the higher insulin level adequately suppresses glucose production and stimulates glucose utilization." The risk of glucocorticoid-induced diabetes increases with the glucocorticoid dosage, duration of therapy, advanced patient age, family history of diabetes mellitus, obesity, certain ethnicity/race, and high blood glucose concentrations before glucocorticoid therapy. The glycemic effect of glucocorticoid use also depends on the route of administration and the type of glucocorticoid.
Management strategies for glucocorticoid-induced diabetes or for the glucocorticoid-induced worsening of diabetes mellitus have not been systematically studied in prospective trials. Dr. Shah says that physicians at Mayo Clinic advise patients:
"The most important goal of therapy for hyperglycemia induced by glucocorticoids is to prevent acute hyperglycemic complications, as well as serious adverse effects from therapy. It is generally believed that a glucose concentration less than 180 mg/dL for most of the day will prevent infections associated with hyperglycemia," says Dr. Shaw.
Patients with mild hyperglycemia (all blood glucose concentrations <200 mg/dL)
Patients with fasting glucose concentration in goal but other glucose concentrations e200 mg/dLd,e
Patients with fasting and daytime blood glucose concentrations e200 mg/dLe