Cellular circadian period length inversely correlates with HbA

The circadian system plays an essential role in regulating the timing of human metabolism. Indeed, circadian misalignment is strongly associated with high rates of metabolic disorders. The properties of the circadian oscillator can be measured in cells cultured in vitro and these cellular rhythms are highly informative of the physiological circadian rhythm in vivo. We aimed to discover whether molecular properties of the circadian oscillator are altered as a result of type 2 diabetes. We assessed molecular clock properties in dermal fibroblasts established from skin biopsies taken from nine obese and eight non-obese individuals with type 2 diabetes and 11 non-diabetic control individuals. Following in vitro synchronisation, primary fibroblast cultures were subjected to continuous assessment of circadian bioluminescence profiles based on lentiviral luciferase reporters. We observed a significant inverse correlation (ρ = -0.592; p < 0.05) between HbA We provide for the first time a potential molecular link between glycaemic control in individuals with type 2 diabetes and circadian clock machinery. This paves the way for further mechanistic understanding of circadian oscillator changes upon type 2 diabetes development in humans. RNA sequencing data and clinical phenotypic data have been deposited at the European Genome-phenome Archive (EGA), which is hosted by the European Bioinformatics Institute (EBI) and the Centre for Genomic Regulation (CRG), ega-box-1210, under accession no. EGAS00001003622.