Endocrine Abstracts

Despite well-established sex differences in blood glucose homeostasis, female mice are highly underrepresented in preclinical diabetes research. Reasons for this may be the milder diabetic phenotype often seen in female mice and/or the assumption that the estrus cycle causes excessive variability in blood glucose concentrations. During this workshop talk we will discuss these points and the importance of accounting for sex differences. Using continuous glucose monitoring technology, we have quantified variation in normal non-fasted blood glucose concentrations in male mice and in female mice in either proestrus/estrus or metestrus/diestrus. We have shown that variation in blood glucose concentrations in male mice consistently exceeded that of female mice, irrespective of stage of estrus. Male mice show a more robust response to the glucose tolerance test than female mice. It has been argued that this heightened response to glucose is required to detect effects of drugs. We investigated the effect of metformin in improving glucose tolerance in both sexes and used the data to carry out sample size calculations. Although the drug effect was smaller in female mice, due to lower variability, the number of mice needed to detect significant differences in females did not differ from males. Not only is it relevant to understand how sex differences may affect data, in some circumstances this may become an important factor in understanding disease processes. To this end, we have studied a model of diabetes with clear sex differences (the KINGS mouse) and consider what this can inform us about diabetes development. Overall, we will consider sex differences in the context of preclinical diabetes research. We will discuss what differences exist, when these differences should be embraced rather than ignored and methods to ensure both sexes are represented in pre-clinical studies.