New-onset diabetes mellitus after kidney transplantation: Current status and future directions

Table 1 Risk factors for new-onset diabetes after transplantation

Non-modifiable	Modifiable
Advanced age	Obesity
African American, Hispanic, or South Asian descent	Sedentary lifestyle
Genetic, e.g., HLA B27	Metabolic syndrome
Adult polycystic kidney disease	Viral infections, e.g., HCV, cytomegalovirus
Previous glucose intolerance, e.g., during pregnancy, steroid therapy for renal or non-renal disease	Corticosteroids
Male donor	Calcineurin-inhibitors (tacrolimus > cyclosporine)
Deceased donor	Sirolimus
	Acute rejection

HCV: Hepatitis C virus; HLA: Human leukocyte antigen.

Table 2 Potential pathogenic mechanisms for drug-induced new-onset diabetes mellitus after transplantation

Immunosuppressive drug	Mechanism for new-onset diabetes after transplantation
Corticosteroids	Increased gluconeogenesis Increased insulin resistance Reduced glycogenesis Decreased insulin release Impaired pancreatic beta cell function
Calcineurin-inhibitors (cyclosporine, tacrolimus)	Reduced glucose uptake Decreased insulin release Reduced insulin gene expression Direct pancreatic beta cell toxicity
Sirolimus	Hypertriglyceridemia ? Decreased pancreatic beta cell proliferation

?: Requires further investigation.

Table 3 Management strategies for new-onset diabetes after transplantation

Prevention strategies	Management strategies
Identification of risk factors (Table 1) with pre-transplant counseling	Regular blood glucose monitoring with appropriate follow-up
Pre- and post-transplant screening: random blood glucose, fasting blood glucose, 2-h oral glucose tolerance test with appropriate follow-up	Multi-disciplinary care
Lifestyle modification: weight control, diet, exercise (subject to dialysis-imposed restrictions)	Lifestyle modification: weight control, diet, exercise
Rapid corticosteroid reduction or avoidance	Rapid corticosteroid reduction
Selective calcineurin-inhibitor use (e.g., cyclosporine instead of tacrolimus)	Conversion of cyclosporine to tacrolimus
? Newer immunosuppressive agents (e.g., alemtuzumab, belatacept)	Oral hypoglycemic agents: metformin, sulfonylureas, meglitinides, dipeptidyl peptidase-4 antagonists (alone and/or in combination)
? Magnesium oxide	Insulin
? Statins	Monitoring for complications

?: Requires further investigation.