Contrary to our hypothesis, short-term dexamethasone treatment did not significantly change levels of TNF alpha, ghrelin, leptin or adiponectin, despite a treatment-related hyperinsulinaemic response . The implication is that GC-mediated insulin resistance does not result from nor elicit major changes in these metabolically active hormones. Data here pertain only to insulin resistance associated with short-term exogenous glucocorticoid treatment, since other etiologies of insulin resistance may result from fundamentally different mechanisms.
Dexamethasone-induced insulin resistance remains a complex mechanism  that is suggested to involve changes in whole body free fatty acid turnover, plasma insulin concentrations  and alterations in both insulin signal transduction  and glucose transporters  Both leptin and adiponectin promote catabolic energy generating processes, such as the mobilisation of triglycerides stores to promote fatty acid oxidation . In line with our earlier report of a lack of effect on fasting NEFA levels , data here argue against a role of aberrant NEFA regulation as a mechanism of glucocorticoid-induced insulin resistance. Also, while whole body lipolysis is different between men and women  there is no gender variation in dexamethasone induced insulin resistance . Hence, this disordered NEFA metabolism reported with dexamethasone-induced insulin resistance may be consequential of changes involving signal transduction and glucose transport.
Circulating levels of TNF alpha show a coordinated increase with obesity during the course of gestational diabetes , and at a physiological level, this adipocytokine alters insulin signal transduction  and secretion . Moreover, adiposity correlates with plasma levels of pro-inflammatory cytokines such as TNF alpha and the systemic acute phase protein C-reactive protein (CRP). In this study we have already reported that dexamethasone therapy resulted in a decrease in CRP levels . Circulating CRP levels are suggested to relate to adipose derived mediators such as leptin and TNFα, and positively correlate with measures of obesity in otherwise healthy adults [24, 25]. In the present analysis we found no association between absolute levels or dexamethasone-related changes in CRP with metabolically active hormone levels.
It is important to place our findings in the context of other studies examining the impact of glucocorticoids on metabolically active hormones and cytokines. Specifically, some human studies suggest that glucocorticoids may decrease ghrelin levels  and increase leptin levels . However, one group reported that fasting obliterated the increase in leptin in response to exogenous glucocorticoids  which may account for the lack of a rise in leptin concentrations with glucocorticoid treatment in our subjects. In longer-term studies, the impact of glucocorticoids on metabolically active cytokines and hormones may be mediated by changes that accompany more chronic glucocorticoid effects, such as obesity , rather than by direct glucocorticoid effects. While it is conceivable that a larger sample size, longer treatment duration, or non-fasting blood assays might have generated positive findings, the highly significant change in insulin sensitivity we observed with dexamethasone reassures us that our study design allowed for detection of major alterations in metabolic cytokines and hormones. Furthermore, the since all subjects who received dexamethasone had undetectable post-treatment cortisol levels, we know that our negative findings were not a result of noncompliance with the intervention. Based on these factors, we suspect that any effects of short-term glucocorticoids on circulating levels of metabolic cytokines and adipokines are likely small, if indeed present at all.
In summary, this randomised placebo-controlled study provides insight into the effects of glucocorticoids, without interference from pathological disease states that are commonly manifest amongst patients on GC therapy. Short-term dexamethasone therapy did not significantly change circulating concentrations of metabolically active hormones, despite increasing insulin resistance.