Endocrine Abstracts

Life on earth is governed by the continuous 24-hour cycle of light and dark. Organisms have adapted to this environment with clear diurnal rhythms in their physiology and metabolism enabling them to anticipate predictable environmental fluctuations over the day and to optimise the timing of relevant biological processes to this cycle. It is of considerable interest that the normal diurnal variation in these processes is lost in the presence of insulin resistance, obesity and diabetes. It is widely appreciated that disruption of an individual’s normal relationship to the 24hour day by shift work schedules contributes to an increased prevalence of metabolic risk factors and an increased risk of obesity, diabetes and cardiovascular disease. Taken together this strongly suggests that disruption of normal diurnal physiological rhythms is of considerable importance in the pathophysiology of the metabolic syndrome and diabetes.

Diurnal rhythms are regulated by molecular circadian clocks and current evidence suggests that interactions between the central and peripheral molecular clocks are important in metabolic, adipocyte and vascular function. Disrupting this process through mutations in the core clock genes or by interfering with the environmental zeitgebers that entrain the central clock appear to modulate the function of cells and tissues leading to the development of the metabolic syndrome and diabetes in animal models.

We have investigated a role for Clock in humans and demonstrated that common polymorphisms in Clock are associated with obesity and the metabolic syndrome in man in several studies. Our data is supported by work from other groups showing that the expression of several of the clock genes in adipose tissue are associated with features of the metabolic syndrome in man and that associations exist between Clock polymorphisms, obesity and non alcoholic fatty liver disease in man, and that Bmal1 polymorphisms are associated with susceptibility to hypertension and Type 2 diabetes in man. Clock polymorphisms have also previously been associated with disturbed sleep patterns, which may in part explain the observation linking sleep disturbance to the metabolic syndrome. Taken together this strongly suggests that disruption of the molecular clock is important in the development of the metabolic syndrome and diabetes.

Note: Due to a technical fault this abstract does not appear in the printed version.