Chrononutrition Applied to Diabetes Management: A Paradigm Shift Long Delayed

The 2017 Nobel Prize in Physiology and Medicine, awarded jointly to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their discoveries of molecular mechanisms controlling the circadian rhythm, offered the opportunity to reflect on how clockwork mechanisms in the body affect the management of diabetes (1).

Circadian rhythmicity relates to all cells in the human body and to the microbiome that coexists within its confines (2,3). Clock genes control intracellular metabolic processes, whereas tissue activity in aggregate is responsive to central clock rhythms entrained by circadian light/dark cycles (Figure 1) (2,3). The circadian system regulates energy homeostasis for the body and is vulnerable to disruption through aberrant feeding/fasting cycles (2,4). Metabolic dysfunction induced by such chrono-disruptive feeding behavior may be corrected by time-restricted feeding in synchronicity with our master resident pacemaker in the suprachiasmatic nucleus of the hypothalamus responsive to immutable celestial cues (2,5–7).

The liver is the central organ involved in nutrient processing and energy metabolism (7,8). It receives amino acids, monosaccharides, and free fatty acids from the gut, along with other trace elements and vitamins, and proceeds to discharge its duties, fabricating tissue and generating energy (7). This process is regulated by hormonal and neurological cues from other organs, most importantly the pancreas, adrenal glands, and gut, and is very much dependent on appropriate timing (3,7,9). Feeding not entrained to innate circadian rhythmicity results in metabolic aberrations and gut dysfunction (3,10,11).

Metabolic aberrations are most frequently expressed as supraphysiologic glucose and triglyceride levels (3,7,10). These affect many organs …