Sleep Duration, Cardiometabolic disease and Mortality: Proteomic links with incident diabetes

Background
Noncommunicable disease, in particular cardiovascular disease (CVD) and diabetes are a major cause of morbidity and mortality in the world. Short and long sleep durations are associated with adverse health outcomes, however, the biological mechanisms for these associations are not fully elucidated. The aim of this thesis is to investigate the association between sleep duration and proteomic markers, respectively, and their associations with incident diabetes, incident coronary heart disease (CHD) and mortality outcomes.

Method
Participants were from the Malmö Diet and Cancer (MDC) study, the MDC cardiovascular cohort (MDC-CC) from the Asia Cohort Consortium (ACC). Paper I investigated the sex-specific associations between sleep duration and incident diabetes and incident CHD in the MDC. Paper II investigated the association between sleep duration and Caspase-8, a proteomic marker of apoptosis, and their respective associations with incident diabetes using the MDC-CC. Paper III investigated the association between sleep duration and mortality outcomes using ACC data. Paper IV investigated the association between sleep duration, proteomic markers, and their respective associations with incident diabetes and incident CHD.

Results
Paper I: sleep durations were associated with incident CHD preceded by incident diabetes in both men and women. Paper II: sleep duration <6 hours was associated with Caspase-8; Caspase-8 was positively associated with incident diabetes and Caspase-8 modified the association between sleep duration and incident diabetes. Paper III: sleep duration was associated with mortality outcomes in both men and women. These associations were modified by age (all-cause mortality) and sex (CVD mortality). Paper IV identified 16 proteomic markers associated with sleep duration quintiles 1, 2, 4, 5 when compared to quintile 3. When combining these proteomic markers to proteomic scores, the score for sleep duration quintile 1 was associated with incident diabetes but not with incident CHD.

Discussion
This thesis suggests a pathway in which short sleep duration through inflammation and apoptotic activity is associated with incident diabetes which in turn increases the risk of future CHD.