PDK4 and Insulin resistance: It has been proposed that niacin-induced activation of the transcription factor FOXO1 in insulin-sensitive tissues, including the liver, skeletal muscle, heart, and adipose tissue, may be responsible for the development of insulin resistance during niacin therapy as some FOXO1 target genes (e.g., pyruvate dehydrogenase kinase Isoform 4, glucose 6-phosphatase, phosphoenolpyruvate carboxykinase, PPARγ coactivator 1, etc.)are known to regulate blood-glucose control and/or insulin sensitivity [19, 38].