Multiple and complex pathways promote the deleterious effects of hyperglycemia in diabetes, ultimately leading to micro- and macrovascular disease. Some of the known mechanisms in diabetic vascular disease may explain the initiation of the "metabolic memory", but fall short if long periods of time are involved.Vascular research has been prolific in the past in finding links between microvascular dysfunction and subsequent macrovascular disease. Thus, this text will extend the current discussion of the "metabolic memory" by including available data from vascular research.The hypothesis proposes that structural and functional changes in the microcirculation interact within the vascular continuum with larger arteries. This interaction may lead to subsequent upstream endothelial dysfunction, atherosclerosis and vascular complications ("Micro/Macro Interaction"). The underlying microvascular structural changes may be more long-term and possibly mediate the "metabolic memory".This hypothesis, that the "not-so new" interaction between micro-and macrovasculature may promote "metabolic memory" effects extends and unifies currently discussed theories.