Effect of dexamethasone on glucose homeostasis in normal and prediabetic subjects with a first-degree relative with type 2 diabetes mellitus.

OBJECTIVE

To determine the effect of a single 8-mg orally administered dose of dexamethasone or placebo on glucose and insulin homeostasis, during an oral glucose tolerance test (OGTT) performed before and 24 hours after the administered dose.

METHODS

In a randomized, double-blind, placebo-controlled study, we conducted experiments in subjects with normal glucose tolerance (NGT) or prediabetes, all of whom had at least one first-degree relative with type 2 diabetes mellitus. Measures of glucose and insulin homeostasis derived from an OGTT before and 24 hours after administration of dexamethasone or placebo were compared in 21 placebo-treated versus 23 dexamethasone-treated subjects with NGT as well as in 23 placebo-treated versus 20 dexamethasone-treated subjects with prediabetes.

RESULTS

Before administration of dexamethasone or placebo, area under the curve (AUC) for glucose and homeostasis model assessment of insulin resistance were higher, and the Matsuda and disposition indices were lower, in the prediabetic versus the NGT group. In both NGT and prediabetic groups treated with dexamethasone, glucose and insulin values at fasting and during OGTT were increased in comparison with placebo-treated groups at 24 hours (P = .001). Dexamethasone treatment in both study groups increased homeostasis model assessment of insulin resistance and AUC glucose and decreased the Matsuda index (P = .001). No significant changes were observed in AUC insulin/AUC glucose or homeostasis model assessment of beta-cell function after dexamethasone treatment in either the NGT or the prediabetic group. The disposition index decreased and was lowest in the prediabetic group after dexamethasone treatment.

CONCLUSION

In a study population in which all subjects had at least one first-degree relative with type 2 diabetes mellitus, those with prediabetes were more insulin resistant and had a lower disposition index than did subjects with NGT. Subjects with prediabetes also had a pronounced decrease in disposition index when challenged with a single 8-mg orally administered dose of dexamethasone.