Glucocorticoid-induced Diabetes Research Articles

Glimepiride successfully treated glucocorticoid-induced diabetes in three women,

Glimepiride successfully treated glucocorticoid-induced diabetes in three women,

Effective use of thiazolidinediones for the treatment of glucocorticoid-induced diabetes

We evaluated the efficacy of a thiazolidinedione in the treatment of diabetes induced by glucocorticoids. We examined the effectiveness of troglitazone in seven patients with long-standing steroid-induced diabetes. Five of the seven subjects were treated with insulin alone, one was treated with both insulin and oral therapy and one was treated with oral therapy alone. The mean insulin dose in six of the seven subjects was 0.66±0.09 units/kg per day. Diabetes status was assessed by measuring serum fructosamine, HgbA1c, oral glucose and meal tolerance tests (OGTT and MTT) at baseline and after treatment for 5–8 weeks with troglitazone 400 mg/day. Troglitazone caused a significant decrease in fructosamine (274±32 vs. 217±22 mmol/l; P<0.01) and HgbA1C (7.8±0.4 vs. 7.2±0.4%; P<0.01) as well as decrements in the areas under the OGTT 2,308±156 vs. 1,937±127 mmol/l; P<0.05) and MTT glucose curves (4694±449 vs. 4057±437 mmol/l; P<0.05). In addition, the area under the insulin curve for the oral glucose tolerance test showed a significant increase from 27,438±4,488 to 41,946±6,048 pmol/l ( P<0.05). Total and LDL cholesterol were also significantly decreased (6.4±0.9 vs. 5.0±0.6 mmol/l and 3.8±0.7 vs. 2.7±0.4 mmol/l, respectively, P<0.05). Fasting leptin values decreased by 23% despite an increase in body weight. Troglitazone is effective in the treatment of glucocorticoid-induced diabetes as manifested by lower measures of glycemia, HgbA1c, and post-prandial glucose values, while the doses of other diabetes medications remained unchanged or were reduced. The insulin-sensitizing drug also produced a marked increase in endogenous insulin secretion in response to glucose, lower total and LDL cholesterol, and decreased fasting leptin despite weight gain. Thiazolidinediones may improve diabetes-related parameters by antagonizing pathways of glucocorticoid-induced insulin resistance and by reversing adverse effects of glucocorticoids on beta cell function.

Roles of insulin resistance and beta-cell dysfunction in dexamethasone-induced diabetes.

The roles of insulin resistance and beta-cell dysfunction in glucocorticoid-induced diabetes were determined in Wistar and Zucker (fa/fa) rats. All Wistar rats treated with 5 mg/kg per d of dexamethasone for 24 d exhibited increased beta-cell mass and basal and arginine-stimulated insulin secretion, indicating insulin resistance, but only 16% became diabetic. The insulin response to 20 mM glucose was normal in the perfused pancreas of all normoglycemic dexamethasone-treated rats but absent in every diabetic rat. Immunostainable high Km beta-cell transporter, GLUT-2, was present in approximately 100% of beta-cells of normoglycemic rats, but in only 25% of beta cells of diabetic rats. GLUT-2 mRNA was not reduced. All Zucker (fa/fa) rats treated with 0.2-0.4 mg/kg per d of dexamethasone for 24 d became diabetic and glucose-stimulated insulin secretion was absent in all. High Km glucose transport in islets was 50% below nondiabetic controls. Only 25% of beta cells of diabetic rats were GLUT-2-positive compared with approximately 100% in controls. Total pancreatic GLUT-2 mRNA was increased twofold suggesting a posttranscriptional abnormality. We conclude that dexamethasone induces insulin resistance, whether or not it induces hyperglycemia. Whenever hyperglycemia is present, GLUT-2-positive beta cells are reduced, high Km glucose transport into beta cells is attenuated and the insulin response to glucose is absent.

Glucocorticoid-Induced Central Diabetes Insipidus in a Case of Malignant Lymphoma.

A 37-year-old man was diagnosed as malignant lymphoma infiltrating in the central nervous system with hypopituitrism and secondary glucocorticoid deficiency. In this case, plasma arginine vasopressin (AVP) increased, but glucocorticoid administration decreased plasma AVP and increased urine volume with a reduction in urinary osmolality, indicative of the presence of glucocorticoid-induced diabetes insipidus. At the terminal stage, plasma AVP did not increase in response to the withdrawal of glucocorticoid and urine volume remained decreased, suggesting the presence of masked diabetes insipidus. Autopsy showed an infiltration of lymphoid cells around the cerebral ventricles and necrosis in the hypothalamo-hypophyseal system. These findings suggested that glucocorticoid might centrally play an important role in the regulation of AVP release, and its deficiency potentiated AVP release.