NR1H4 and type 2 diabetes mellitus: Patients with T2DM appear to have elevated serum BA concentrations in both the fed/fasting states, irrespective of the intensity of insulin therapy (Fig. 15).366–369 This is thought to occur due to hyperglycemic-induced FXR-independent hyperacetylation of the CYP7A1 promoter allowing for increased expression.370 In addition to an expanded BA pool size, BA-centric mechanisms reinforce the key T2DM characteristics of impaired insulin sensitivity and overactive gluconeogenesis.