Change in glucose metabolism after long-term treatment with deflazacort and betamethasone

Abstract

Summary.We have compared the long-term effects of different corticosteroids on glucose metabolism by carring out a 75 g oral glucose tolerance test in 27 subjects before and after the administration of deflazacort or betamethasone for two months in random balanced sequence. Fasting plasma glucose and insulin concentrations were significantly higher after betamethasone, whereas deflazacort increased only fasting plasma insulin.After oral glucose there were significant increases in blood glucose and insulin after betamethasone compared with deflazacort. These results suggest that the degree of glucose intolerance and insulin resistance depends on the steroid used and on the dose given, although long-term treatment with deflazacort has a smaller effect on glucose metabolism than betamethasone.Key words: Glucocorticoids, Glucose metabolism; deflazacort, betamethasone, insulin resistance Glucocorticoids cause gtucose intolerance in healthy subjects [1-5] by enhancing liver production and reducing peripheral utilization. This is accompanied by hyperinsulinaemia and is regarded as a condition of insulin resistance [6], characterized by a postreceptor defect of insulin action [7]. However, both glucose intolerance and insulin resistance in response to glucocorticoids depend not only on the dose and duration of treatment but also on the type of compound used [8,9]. Deflazacort is less diabetogenic than prednisone in healthy subjects [10], in those with a positive family history of NIDDM [11], and those with IDDM [12]. Furthermore, a single dose of betamethasone has a significantly greater effect than prednisone and deflazacort on the response to oral glucose loading in healthy subjects [13].We have compared the effects of betamethasone and deflazacort, both given for 2 months, on glucose tolerance in non-diabetic patients. Materials, methods, and subjectsWe studied 27 patients requiring steroids for different disorders (Table 1) who had not taken other steroids. They were classified as non-diabetic according to the NDDG criteria [14] after an oral glucose tolerance test (75 g of glucose). 2"he test was repeated about 60 and 120 days after the start of treatment with deflazacort (mean duration 60 (2) days), followed or preceded by betamethasone (mean duration 61 (2) days), according to a balanced random design. The dosages were the least required to control the patient's symptoms and the average time required to titrate an affective clinical dose at the beginning of the first treatment period was 3.03 (0.41) days (3.07 (0.64) for deflazacort, 2.9 (0.53) for betamethasone). The dosage equivalents were chosen arbitrarily on the basis of bioequivalence, calculated from studies of endogenous adrenal suppression [2], in order to produce equal anti-inflammatory and glucogenic effects of the two drugs.The final dose was given 24 h before the two tests. Since indefinite treatment was necessary, there was no washout period and we did not assess the reversibility of the results on withdrawal. Measures related to the course of these...

Serum glucose, insulin and C-peptide response to oral glucose after intravenous administration of hydrocortisone and methylprednisolone in man

“…These findings indicate that glucose intolerance induced by a single i.v. injection of glucocorticoids is dependent not only on the type of steroid, but also on the dose administered, confirming previous results obtained using the oral route (Bruno et al 1992). Second, insulin resistance was more evident for MP than HC and mean insulin values were significantly higher after MP than HC, both fasting or expressed as areas under the insulin curve.…”

Twenty‐four‐hour profiles of plasma glucose, insulin, C‐peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short‐term, medium‐dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action

“…This contrasts with our findings where our subjects with NGT did not demonstrate any tendency towards prednisone‐induced suppression of insulin secretion, suggesting that the ability to compensate for the decrease in insulin action with corresponding increases in insulin secretion may be related to the severity of the underlying β‐cell defect and higher doses of prednisolone used. Whether our findings can be generalized to other forms of GCs is not clear, but it is noteworthy that bethamethasone 31 and dexamethasone 32 have been previously shown to induce greater glucose intolerance and insulin resistance than prednisone and deflazacort 31,33 in healthy humans.…”

Deflazacort

“…Lower dose shown is for children Bruno et al (1992) (http://www.bnf.org/Index.htm). The dose equivalence to prednisolone is 1:1.2 (deflazacort 6 mg: prednisolone 5 mg).…”