Background Impaired glucose homeostasis is a key feature in the development of a variety of metabolic diseases including type 2 diabetes (T2D), metabolic syndrome facets, and ageing. The cornerstone for treatment of risk-factors for insulin resistance remains diet and exercise prescription (prior to medicating), however these have poor rates of adherence. As such, there remains a need to identify safe and effective interventions which could help to combat insulin resistance. The leucine metabolite, beta-hydroxy beta-methylbutrate (HMB), is a bio-active nutraceutical with anabolic properties and contentious effects on insulin sensitivity in animal models (1,2). Therefore the aim of this study was to evaluate the impact of HMB adjuvant to an oral glucose challenge upon plasma glucose/insulin kinetics in older and younger men. Methods Groups of 10 younger (18-35y) and 10 older (65-85y) healthy men were recruited. Subjects underwent two 3-hour 75g oral glucose tolerance tests (OGTT’s), spaced >7d apart. During one OGTT, glucose was administered with 3g oral HMB and during the other OGTT glucose was administered alone in a randomised-order. Blood was drawn periodically for the quantification of blood glucose (YSI) and plasma insulin (ELISA). Statistical analysis was performed via 2-way ANOVA by age and treatment, with Sidak’s multiple comparison post-hoc testing. Data is presented as mean (SD). Significance was set at p<0.05. Results In younger men, HMB reduced the insulin area-under-the-curve (AUC) (4158 (SD:2753) vs. 5836 (4451) mU/L/180min; p=0.02) with no difference in glucose AUC (1127 (147) vs. (1142 (122) mmol/Lx180min; p=0.8). This led to a trend towards an increase in the Cederholm index of insulin sensitivity (62.7 (13.9) vs. 55.1 (11.0); p=0.08)) with HMB. In older men, HMB had no effect on the insulin (5712 (2488) vs. 5980 (2854) mU/Lx180min; p=0.88) or glucose (1426 (194) vs. (1409 (180) mmol/Lx180min; p=0.84) AUC, and as such there was no difference in their Cederholm index (57.9 (14.2) vs. 55.6 (10.7); p=0.72). Conclusions HMB improved insulin sensitivity following a single glucose load in young men; however this does not appear to be sustained into older age, limiting the potential for HMB as a supplement to combat insulin resistance (given the incidence of this rises sharply with advancing age). Nonetheless, the positive effects in younger people indicate the possibility that HMB may form a potential treatment for younger ‘at-risk’/T2D populations.