Glycogen is a highly branched polymer of glucose, functioning as a blood-glucose buffer. It comprises relatively small b-particles, which may be joined as larger aggregate a-particles. The size distributions from size-exclusion chromatography (SEC, also known as GPC) of liver glycogen from non-diabetic and diabetic mice show that diabetic mice have impaired a-particle formation, shedding new light on diabetes. SEC data also suggest the type of bonding holding b-particles together in a-particles. SEC characterisation of liver glycogen at various time points in a day/night cycle indicates that liver glycogen is initially synthesised as b-particles, and then joined by an unknown process to form a-particles. These a-particles are more resistant to degradation, presumably because of their lower surface area-to-volume ratio. These findings have important implications for new drug targets for diabetes management.