Table 2.

Drug-induced NODAT: potential pathogenic mechanism(s)

Immunosuppressive agent	Pathogenic mechanism(s)	Comments
Corticosteroids	↓ Peripheral insulin sensitivity Inhibit pancreatic insulin production and secretion ↑ Hepatic gluconeogenesis Promote protein degradation to free amino acids in muscle, lipolysis	Dose-dependent Impact of complete withdrawal of chronic low-dose steroids unclear Potential ↓ NODAT risk in steroid-free regimens
Cyclosporine	↓ insulin secretion (CsA < Tac) ↓ insulin synthesis ↓ β-cell density	Dose-dependent, Diabetogenic effect ↑ with ↑ steroid dose*
Tacrolimus	↓ insulin secretion (Tac > CsA) ↓ insulin synthesis	Dose-dependent, Diabetogenic effect ↑ with ↑ steroid dose*
Sirolimus	↑ Peripheral insulin resistance Impair pancreatic β-cell response	↑ Diabetogenicity when use with CNIs

Note:

^*Demonstrated in some but not all studies.

Abbreviation: CNI, calcineurin inhibitors.