Determinants of insulin resistance in renal transplant recipients

Insulin resistance is considered to play an important role in the development of cardiovascular disease, which limits long-term renal transplant survival. Renal transplant recipients are more insulin-resistant compared with healthy controls. It is not known to date which factors relate to this excess insulin resistance. Therefore, we investigated which factors are related to insulin resistance long-term after renal transplantation.

All renal transplant recipients at our outpatient clinic with a functioning graft for more than one year were invited to participate. We excluded diabetic recipients. Recipient, donor, and transplant characteristics were collected as putative determinants. We used fasting insulin, homeostasis model assessment index, and McAuley's index as valid estimates of insulin resistance. Linear regression models were created to investigate independent determinants of all indexes.

A total of 483 recipients (57% male, 50+/-12 years) were analyzed at a median (interquartile range) time of 6.0 (2.6-11.6) years posttransplant. The most consistent determinants across all three indices were body mass index (P<0.001), waist-to-hip ratio (P<0.001), and prednisolone dose (P<0.05). Independent associations were present for total cholesterol (P<0.001), high-density lipoprotein cholesterol (P<0.001), creatinine clearance (P<0.05), recipient age (P<0.001), and gender (P< or =0.002). No independent associations were present for transplant-related factors such as acute rejection treatment or cytomegalovirus seropositivity.

Our results indicate that obesity, distribution of obesity, and prednisolone treatment are the predominant determinants of insulin resistance long term after transplantation. Insulin resistance after renal transplantation could be managed favorably by weight and prednisolone dose reduction, which may reduce cardiovascular disease.