Different levels of circadian (de)synchrony -- where does it hurt?

A network of cellular timers ensures the maintenance of homeostasis by temporal modulation of physiological processes across the day. These so-called circadian clocks are synchronized to geophysical time by external time cues (or zeitgebers). In modern societies, natural environmental cycles are disrupted by artificial lighting, around-the-clock availability of food or shiftwork. Such contradictory zeitgeber input promotes chronodisruption, i.e., the perturbation of internal circadian rhythms, resulting in adverse health outcomes. While this phenomenon is well described, it is still poorly understood at which level of organization perturbed rhythms impact on health and wellbeing. In this review, we discuss different levels of chronodisruption and what is known about their health effects. We summarize the results of disrupted phase coherence between external and internal time vs. misalignment of tissue clocks amongst each other, i.e., internal desynchrony. Last, phase incoherence can also occur at the tissue level itself. Here, alterations in phase coordination can emerge between cellular clocks of the same tissue or between different clock genes within the single cell. A better understanding of the mechanisms of circadian misalignment and its effects on physiology will help to find effective tools to prevent or treat disorders arising from modern-day chronodisruptive environments.

Leptin and the GA genotype of rs2167270 of the LEP gene increase the risk of prediabetes.

Prediabetes is a precursor stage that frequently develops to definitive type 2 diabetes mellitus (T2DM). Therefore, identifying individuals with prediabetes can allow for early intervention measures that delay or prevent disease progression to T2DM. Several biochemical changes appear to be associated with prediabetes, including an increase in the serum levels of leptin. In Jordan, this association has not been previously investigated. In the present study, the serum levels of leptin were measured in 122 prediabetes subjects and 122 controls. Furthermore, the genotypes of three single nucleotide polymorphisms in the LEP gene (rs7799039, rs2167270 and rs791620) were investigated for their association with prediabetes using PCR-restriction fragment length polymorphism. The results revealed a significant increase in serum leptin levels in the prediabetes group. It was also shown that the GA genotype and the A allele of rs2167270 were significantly associated with an increased risk of prediabetes (P<0.05). These findings were shown to be independent of body mass index, waist circumference and serum glucose levels. To the best of our knowledge, the present study is the first in Jordan to have reported an association between serum leptin levels and the GA genotype of rs2167270 with an increased risk of prediabetes, identified both in the univariate and multivariate models.

Association of Adiponectin and rs1501299 of the ADIPOQ Gene with Prediabetes in Jordan.

Type 2 diabetes mellitus (T2DM) is a worldwide health problem caused by resistance to insulin action. This chronic debilitating diseaseis preceded by a stage, known as prediabetes, in which a healthy lifestyle can delay the disease. The discovery of biochemical changes in prediabetes is important to identify individuals at risk of developing T2DM and in explaining disease pathogenesis. Adiponectin is secreted by fat cells and is linked with insulin resistance. Adiponectin levels are dysregulated in prediabetic subjects. This relationship had not been tested in Jordan. We recruited 130 subjects with prediabetes and 130 control subjects. We measured serum levels of adiponectin and genotyped subjects for three single nucleotide polymorphisms (SNPs) in the ADIPOQ gene; rs266729, rs1501299 and rs2241766. In multivariate analysis, we found that serum adiponectin lowers the risk of prediabetes (p = 0.002; odds ratio (OR), 0.764; 95% confidence interval (CI), 0.646⁻0.905). The rs1501299 SNP of the ADIPOQ gene was associated with prediabetes in our population (p = 0.041). Specifically, in multivariate analysis, the GT genotype of rs1501299 increased the risk of prediabetes (p = 0.010; OR, 2.350; 95% CI, 1.231⁻4.486) as well as the TT genotype (p = 0.006; OR, 4.774; 95% CI, 1.551⁻14.693). Our findings indicate that serum adiponectin and SNPs in the ADIPOQ gene are associated with prediabetes in Jordan.