Type 2 diabetes mellitus is an epidemic that threatens the health of the
Sleep-wake rhythm disorders are common in an aging population. Their link to
diabetes has recently been established
More than a decade passes by in many individuals from first risk factors to
overt type 2 diabetes
Modern European lifestyles have dramatically changed the daily rhythm of life. This daily sleep-wake cycle is called “circadian (circa = about; dian from Latin dies = day; ie.e. about one day long) rhythm”. In the modern world, physical activity, food intake and light exposure are no longer restricted to daytime hours, and sleep duration has been continuously reduced over the last century. These changes have been fuelled by social and economic demands, but developing evidence indicates that this comes at a price of increased cardiometabolic ill health. In the project EuRhythDia we aim to develop understanding of the importance of circadian regulation of metabolism in normal health, and in the development of cardiometabolic risk associated with obesity, type 2 diabetes and cardiovascular disease.
The scientific evidence linking circadian rhythm disorders to type 2 diabetes mellitus are manifold: In animal studies disruptions in those genes that are known to regulate the circadian rhythm lead to the development of a phenotype similar to human type 2 diabetes/obesity. Although there are no studies in human subjects yet that causally relate clock genes to the development of type 2 diabetes, members of our consortium have reported that inborn genetic variation in certain genes relating to the circadian clock are associated with the metabolic syndrome in man, and epidemiological data has shown that shift workers – who are known to experience disrupted circadian rhythms – are at increased risk of developing type 2 diabetes mellitus. In one study a group of 402 night shift workers were compared with 336 pure daytime workers. During 4 years of follow-up, night shift workers had a 5-fold higher probability of developing type 2 diabetes or obesity than daytime workers. In another study, a large group of 1,529 workers, among which were 309 rotating shift workers, were studied. Shift workers had a 77% higher probability of developing type 2 diabetes mellitus than non-shift workers.
Considering these findings from previous studies, there is a large group of potential risk groups within the European population. These span from night shift workers (an extreme of lifestyle associated with disrupted sleep/wake rhythms) to rotating shift workers, from juveniles who voluntarily stay up late, thereby adopt a lifestyle disrupting their circadian rhythms, to elderly people who have a high prevalence of sleeping disorders, from menopausal women affected by sleep disorders and disturbed circadian rhythms to an increasing number of long-distance travellers suffering from jet lag. This underscores the fact that a large and increasing part of the European population is affected by lifestyle conditions associated with disruptions of circadian rhythms, increasing their risk of obesity and cardiometabolic disease.
Thus, interventions to prevent the progression of insulin ristance to overt type 2 diabetes mellitus are urgently needed.
And indeed, whilst progress has been made in the pharmacological treatment of type 2 diabetes mellitus in recent years, no convincing specific strategies have been proposed for the prevention of this disease, except general recommendations regarding weight loss, regular exercise, and a healthy lifestyle. It has always been assumed that these approaches are effective because they influence energy balance in whatever manner they are applied. However, exciting recent data from experimental and clinical research strongly supports the view that weight gain, for example, disrupts the endogenous clock and that this disruption puts metabolism out of time with our energy needs creating a strong determinant of type 2 diabetes risk. This suggests that lifestyle intervention might benefit from consideration of the impact of the timing of application during the day.