These disparate results may be ascribed to the difficulty of controlling confounding variables in a human population; for example, obese and diabetic individuals generally consume more diet soft drinks and APM containing products than Life Science Reagents non-diabetics. For this reason, we chose to examine the impact of chronic, low-dose APM consumption in a lean and diet-induced obese animal model where confounding variables could be strictly controlled. Results of the present study show APM to differentially affect measures associated with metabolic disease. There is no doubt that APM reduces the energy density of the foods or beverages it is added to. However, there is interest in whether this reduction results in lower overall energy intake, body mass and adiposity. Analysis of energy consumption in this study showed APM consuming animals to reduce their energy intake by,17 and 25% for lean and HF fed animals respectively. This reduction in energy intake occurred in spite of identical diet composition within groups, as APM was only administered in the drinking water. Reductions in energy intake with APM resulted in lower body mass in both CH and HF. In spite of this, there were discrepant effects of APM on body fat; the percentage increased in CHA, yet resulted in a lower body fat gain in HFA compared to their respective water consuming controls. To gain insight into the impact of these alterations on metabolic health, an OGTT and ITT were performed. Fasting hyperglycemia was evident with APM ingestion regardless of diet. Furthermore, the AUC for glucose during the ITT was elevated in APM rats in both the CH and HF diet conditions. By administering a high physiological insulin bolus, we were able to show a reduced ability of animals to clear endogenous glucose with APM, either due to a reduction in peripheral insulin sensitivity or an impaired insulin-mediated suppression of net hepatic glucose output. Given the OGTT results showed no difference with APM, the latter hypothesis is likely correct. To explore the potential mechanism by which APM affects metabolism, gut microbiota and serum metabolomics analyses were performed. Increasing evidence points to a significant interaction between the gut microbiome, the metabolomic profile and the development of metabolic disease states. We found HFW, but not HFA, to be associated with a more obesity and diabetes-associated microbiota profile as defined by a higher Firmicutes:Bacteroidetes ratio. This indicates that APM treatment may have provided a protective effect against HF-induced changes in microbial phenotype, although this is likely a simplistic view given that high throughput sequencing now allows for greater insight down to the species level.