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
Epidemiological evidence indicates that obesity-related insulin resistance predates the development of frank type 2 diabetes by up to 20 years, but that during this important period, risk of cardiovascular disease begins to emerge. As individuals cycle from insulin resistance with normal fasting blood glucose levels to beta cell failure and frank hyperglycaemia, further increases in cardiovascular risk occur and, following the emergence of type 2 diabetes, the risk of microvascular complications develops. This understanding is important because the long prodromal phase before diabetes appears provides opportunities for lifestyle interventions to ameliorate disease progression. In addition, this model supports the view that clustering of cardiometabolic risk prior to the development of diabetes increases cardiovascular disease, whilst hyperglycaemia, when diabetes appears, further increases cardiovascular risk and additionally increases microvascular complications of diabetes.
Type 2 diabetes is a lifestyle disease; therefore, the causal chain of events leading to the manifestation of type 2 diabetes after several decades of prodomal states can best be interrupted at its very beginning:
lifestyle —> circadian rhythm disruption —> metabolic and vascular dysfunction —> overt diabetes and cardiovascular disease
Lifestyle intervention in the context of this project is meant to re-adjust the circadian clock and thereby improve metabolic state. One well-known means of shifting the phase of circadian rhythms is light therapy, using daylight-like light sources. One of the project partners – Lumie – will provide daylight sources for interventional studies to investigate the effect of this lifestyle intervention on circadian rhythm phasing, glucose metabolism and insulin resistance.
Another often used type of lifestyle recommendation is physical exercise. Many different strategies have been tested to improve cardiometabolic health by physical exercise. We will aim to assess the effects of timed exercise intervention, by comparing the influence of morning exercise versus evening exercise both in shift workers and in prediabetic subjects.
It is often assumed that the effects of light exposure on circadian rhythms are mediated by melatonin, a hormone secreted by the pituitary gland in the brain during the dark phase. We will test whether timed administration of melatonin will improve circadian rhythm phasing and glucose metabolism in subjects at-risk.
These studies undertaken with funds by the European Union will help to better understand some novel molecular links between environmental factors, work life, and diabetes mellitus type 2.