Time dictates: emerging clinical analyses of the impact of circadian rhythms on diagnosis, prognosis and treatment of disease

Abstract

Since the advent of modern molecular tools, researchers have extensively shown that essential cellular machineries have robust circadian (roughly 24 hours) variations in their pace. This molecular rhythmicity translates directly into time-of-day-dependent variation in physiology in most organ systems, which in turn provides the mechanistic rationale for why timing on a daily basis should matter in many aspects of human health. However, these basic science findings have been slow to move from bench to bedside because clinical studies are still lacking to demonstrate the importance of timing. Therefore, it has not been clear how physicians should incorporate knowledge of natural 24-hour rhythms into routine practice. This review is a brief summary of results from recently completed clinical studies on hypertension, myocardial infarction, diabetes mellitus, and adrenal dysfunction that highlights new evidence for the emerging importance of circadian rhythms in diagnosis, prognosis and treatment of disease.

Keywords: Circadian rhythm; NSBP; dawn phenomenon; ischaemia onset time; near-physiological hormone replacement.

Fig. 1

Mean 24-h continuous glucose profiles of T2DM patients on diet alone treatment with the absence (solid curve) or with the presence of a dawn phenomenon (dashed curve), and of patients taking oral medication in the presence of a dawn phenomenon (dotted curve). Arrows show meal times. Figure adapted from reference #.

Fig. 2

Mean 24-h cortisol profiles of healthy subjects (solid curve), of patients with adrenal insufficiency treated with either conventional therapy (dotted curve) or with programmed infusion therapy (dashed curve). Dark bars represent periods of darkness. Figure adapted from reference #.