This review aims to summarize the knowledge about the relationship between circadian rhythms and their influence on the development of type 2 diabetes mellitus (T2DM) and metabolic syndrome. Circadian rhythms are controlled by internal molecular feedback loops that synchronize the organism with the external environment. These loops are affected by genetic and epigenetic factors. Genetic factors include polymorphisms and mutations of circadian genes. The expression of circadian genes is regulated by epigenetic mechanisms that change from prenatal development to old age. Epigenetic modifications are influenced by the external environment. Most of these modifications are affected by our own life style. Irregular circadian rhythm and low quality of sleep have been shown to increase the risk of developing T2DM and other metabolic disorders. Here, we attempt to provide a wide description of mutual relationships between epigenetic regulation, circadian rhythm, aging process and highlight new evidences that show possible therapeutic advance in the field of chrono-medicine which will be more important in the upcoming years.

Defects of the SHOX gene (short stature homeobox-containing gene), localized in the pseudoautosomal region 1 (PAR1) have been associated with Léri–Weill dyschondrosteosis (LWD; MIM ID: 127300) (heterozygous microdeletion or causal point mutation), Langer syndrome (MIM ID: 249700) (homozygous defect), and idiopathic short stature (ISS; MIM ID: 300589). The same pathological phenotype can be caused by an aberration in flanking regulatory sequences of SHOX gene (f.e. Flanagan et al.2002). Defects of the SHOX gene or its regulatory sequences are the origin of LWD in about 70% of patients (Kosho et al.1999; Ogata et al.2002; Hirschfeldova et al.2012) and in about 3% of ISS patients (f.e. Rappold et al.2002). What we do not know is the role of common SHOX gene sequence variants and a small common ∼4.9-kb deletion (MLPA kit P018 SHOX, probe L05101) ∼200 kb downstream of SHOX gene near its known regulatory sequences (f.e. Benito-Sanz et al.2006; Hirschfeldova et al. ...