60 hours of fasting and it's relationship with insulin resistance and mitochondrial function.

Skeletal muscle mitochondrial dysfunction has been linked to the development of insulin resistance and type 2 diabetes mellitus. We have suggested that muscle mitochondrial dysfunction may result from lipotoxicity: fat accumulation in skeletal muscle – as observed in insulin resistance and diabetes - could lead to impaired mitochondrial function. Interestingly, prolonged fasting (short-term ‘starvation’) also results in intramyocellular lipid accumulation and insulin resistance. Whether the mechanisms underlying are comparable, is unknown and aim of the present study.

Prolonged fasting-induced lipid accumulation accompanied by increased levels of DAG and ceramide, will interfere with insulin signaling explaining the insulin resistant glucose uptake.
High levels off FFA might cause a decreased oxidative capacity

Insulin sensitivity is assesed after 60 hours, biopsies are taken after 60 hours in basal and insulin stimulated condition.
Additional blood samples are taken after 12,36 and 60 hours.

12 healthy subjects wiil undergo in random order a 60h fast (calorie-free drinks only (S)) or a control diet (50-35-15% of energy as CHO, fat and protein (FED)). During the study, subjects stayed in a respiration chamber to measure energy expenditure and substrate oxidation. Insulin-sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Muscle biopsies and blood samples were taken after each intervention period in basal and insulin-stimulated conditions. Oxidative capacity is measured with an oxygraph.