A) New Onset DIABETES MELLITUS (DM) - Less Than 1% to 46% 1) Several Case Reports of Diabetic

Hyperglycemia 1) INCIDENCE a) New onset DIABETES MELLITUS (DM) - less than 1% to 46% 1) Several case reports of diabetic KETOACIDOSIS and HYPEROSMOLAR COMA have been reported in patients treated with corticosteroids (Braithwaite et al, 1998). 2) In a case-controlled study (n=11,855), the estimated relative risk for developing hyperglycemia which requires treatment was 2.2 in patients receiving a corticosteroid compared with non-users. As the average daily dosage of corticosteroid increased, the risk for hyperglycemia also increased. Using standardized dosage equivalents of hydrocortisone, the odds ratio for developing hyperglycemia was 1.77 for a dosage of 1 to 39 mg/day compared to 10.34 for a dosage of 120 mg/day or more (Chan et al, 1996). 2) OUTCOME a) Severe (mortality reported). 1) Isolated cases of fatalities were reported in patients with ketoacidosis or hyperosmolar coma; however, the majority of patients can continue the corticosteroid with treatment of hyperglycemia (Braithwaite et al, 1998). 3) ONSET/DURATION a) EARLIEST ONSET 1) New onset DM usually within the first 6 weeks. a) Metabolic emergencies may occur earlier or later (Braithwaite et al, 1998). b) DURATION OF SYMPTOMS (with treatment) 1) Once the insulin dosage is adjusted to achieve good glycemic control, patients become asymptomatic (Braithwaite et al, 1998). 4) MONITORING PARAMETERS a) Hyperglycemic symptoms: Patients should be instructed that if excessive thirst, frequent urination, fatigue, or weight loss occur, they should contact their physician (Braithwaite et al, 1998). b) Fasting blood glucose - every 1 to 2 weeks during initiation of corticosteroid (Braithwaite et al, 1998). c) Preprandial urine for glucose (second-voided) - twice daily initially and then 3 times per week after the first 4 weeks (Braithwaite et al, 1998). 5) CLINICAL MANAGEMENT a) PROPHYLACTIC MEASURES 1) For patients with poorly controlled DM, control preferably with insulin should be achieved before initiating a corticosteroid (Hoogwerf & Danese, 1999; Braithwaite et al, 1998). b) PHARMACOLOGIC 1) The following treatment guidelines assume use of a moderate-to-high dose glucocorticoid that is the equivalent of prednisone 30 mg/day or higher. a) New onset DM - When SHORT DURATION CORTICOSTEROID THERAPY (ie, rapidly tapering therapy for less than 2 weeks or single injection) is planned, preprandial blood glucose concentrations of 120 to 200 mg/dL are acceptable, and treatment of hyperglycemia is usually not necessary (Braithwaite et al, 1998). When LONG DURATION CORTICOSTEROID THERAPY (ie, more than 4 weeks) is planned, target ranges for glycemic control should be the same as for the general diabetic population (ie, 80 to 120 mg/dL premeal, 100 to 140 mg/dL at bedtime). In general, sulfonylureas do NOT adequately control glucocorticoid-induced diabetes. When high-dose glucocorticoids are started, blood glucose tends to rise despite addition of a sulfonylurea; therefore, insulin therapy is usually needed (Braithwaite et al, 1998). b) Pre-existing DM - When SHORT DURATION CORTICOSTEROID THERAPY (ie, rapidly tapering therapy for less than 2 weeks or single injection) is planned, preprandial blood glucose concentrations of 120 to 200 mg/dL are acceptable; therefore, most patients can continue current therapy. If hyperglycemia becomes problematic, regular insulin supplements before meals may be used (Braithwaite et al, 1998). When INTERMEDIATE DURATION CORTICOSTEROID THERAPY (ie, short-term therapy with high fixed dose or 2-to 4-weeks of therapy) is planned, good glycemic control should be achieved before starting the glucocorticoid. In these patients, good glycemic control generally requires rapid upward adjustment of daily insulin doses. Generally, a mixture of an intermediate/regular insulin is given in the morning and evening with premeal supplements of regular insulin. The daily intermediate/regular insulin dosage is adjusted until glycemic control is achieved (Braithwaite et al, 1998). When LONG DURATION CORTICOSTEROID THERAPY (ie, more than 4 weeks) is planned, target ranges for glycemic control should be the same as for the general diabetic population (ie, 80 to 120 mg/dL premeal, 100 to 140 mg/dL at bedtime). If before initiation of the corticosteroid the premeal blood glucose is above 140 mg/dL, many patients will require insulin therapy. When high-dose glucocorticoids are started, blood glucose tends to rise despite addition of a sulfonylurea; therefore, insulin therapy is usually required (Braithwaite et al, 1998). 6) PREDISPOSING RISK FACTORS a) DOSE-RELATED 1) Yes (Hoogwerf & Danese, 1999; Braithwaite et al, 1998). b) DURATION-RELATED 1) Yes (Braithwaite et al, 1998). c) AGE GROUP 1) Older patients (Hoogwerf & Danese, 1999). d) ETHNIC GROUP 1) Ethnic minorities (Hoogwerf & Danese, 1999). e) DISEASE STATES 1) Impaired fasting glucose tolerance, impaired glucose tolerance, family history of DM, or history of gestational DM (Braithwaite et al, 1998). 7) PROBABLE MECHANISM a) Pharmacologic (extension of the expected effects of a drug) 1) Corticosteroids cause peripheral insulin resistance (Hoogwerf & Danese, 1999; Braithwaite et al, 1998). Corticosteroids also cause gluconeogenesis, and with prolonged therapy, pancreatic release of glucagon increases which promotes glycogenolysis (Hoogwerf & Danese, 1999; Gilman et al, 1990; Olefsky & Kimmerling, 1976; Azarnoff, 1975; Spenney et al, 1969; Blereau & Weingarten, 1964; Short, 1964). 8) DOCUMENTATION a) QUALITY 1) Fair 9) CASE REPORTS a) Precipitation of hyperosmolar DIABETES was reported in a 62-year-old woman while receiving alternate-day prednisone therapy (60 mg every other day) for 8 months. The patient also received hydrochlorothiazide for 4 months. A precipitating event or previous abnormal glucose tolerance tests were not identified. However, the patient had a family history of diabetes (Lohr, 1984). b) Hyperglycemic COMA secondary to prednisone administration has been reported (Pierce & O'Brien, 1969). A 72-year-old female received prednisone 60 to 80 mg daily over a period of 3 months for idiopathic autoimmune hemolytic anemia. The patient developed glycosuria with symptoms of thirst, lethargy, and vomiting after 1 month of therapy. The patient collapsed and gradually became comatose. Urine specific gravity was 1.030 with 3+ sugar. Blood glucose was 1256 mg%. The patient recovered following IV fluids and insulin in a period of 72 hours.