The circadian clock system (from Latin “circa diem”, about a day) allows most of the organisms on Earth to anticipate periodical changes of geophysical time. Nearly all the cells in our body comprise molecular clocks that regulate and adjust metabolic functions to a 24-hour cycle of day-night changes. Increasing evidence indicates that misalignment between external stimuli and internal clocks stemming from irregular working schedules, frequent time zone changes, or ageing, have a significant impact on the development of metabolic diseases in human beings, including type 2 diabetes (T2D). Importantly, the organism needs a functional coupling between clocks that are located in different organs in order to function as a whole. Hence, inter-organ circadian desynchrony may also perturb glucose homeostasis. Transplantation of metabolic organs carrying functional clocks to the host with dysfunctional oscillators (associated with aging and/or metabolic disease) represents a model of such inter-organ circadian misalignment due to circadian autonomy of the graft. We hypothesize that circadian autonomy of metabolic organs from rest of the body clocks may lead to circadian misalignment between metabolic tissues, contributing to the pathogenesis of T2D, including post-transplant diabetes mellitus (PTDM).