The researchers next turned their attention to treatment-induced metabolic dysfunction. They used the glucose kinetics test to assess arthritis-induced, prednisolone-induced and ORG 37663-induced metabolic dysfunction. The investigators found that prednisolone treatment significantly reduced insulin sensitivity in both non-arthritic and arthritic mice. Although ORG 37633 also lowered blood glucose concentrations in arthritic mice, the effect was slight when compared with placebo treatment. Treatment with prednisolone or ORG 37663 resulted in a decrease in C peptide concentrations in both arthritic and non-arthritic mice. The investigators note that although mice treated with prednisolone did develop insulin resistance, they did not experience hyperglycemia, suggesting that the mice have a highly adaptive compensatory mechanism.
In their conclusion, the authors write, “we successfully integrated the whole body glucose test in the CIA mice model, which enabled us to measure both efficacy and metabolic (adverse) effects of (experimental) GCs in a chronic in vivo inflammatory setting. Thereby, it may prove a useful translational model for compound-induced metabolic derangements in patients suffering from RA [rheumatoid arthritis] or other (auto) immune diseases. This study showed that both inflammation and glucocorticoids affect insulin secretion and sensitivity but this did not lead immediately to the development of hyperglycemia and type 2 diabetes mellitus.”(posted 10/31/14)
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
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