Impending hyperglycemia in normoglycemic renal transplant recipients--an experimental predictive surrogate

beta-Cell dysfunction and insulin resistance combine to cause new-onset diabetes after transplantation. The product of these two parameters, quantitatively measured as disposition index (DI), is a mathematical constant in normoglycemia and declines in advance of impending hyperglycemia. The aim of this study was to derive a simple surrogate for the DI to expose predysglycemic abnormalities posttransplantation.

First-phase insulin secretion and sensitivity were determined by mathematical minimal model analysis of 58 frequently sampled, intravenous glucose tolerance tests in 58 non-diabetic renal transplant recipients and correlated against surrogate indexes based on fasting blood samples. Products of insulin secretion/resistance indexes were correlated against calculated DI, regression analysis performed for hyperbolic compatibility, autocorrelation studies conducted, and surrogates tested in various subgroups of renal transplant recipients to ensure robustness in a heterogeneous group.

The best correlation was achieved with "HOMA(sec) (first-phase insulin secretion)xMcAuley's index (insulin resistance)" (r=0.594, P<0.001). Regression analysis was consistent with a mathematical hyperbola (ln HOMA(sec) vs. ln McAuley's index, r=-0.639 [95% confidence interval, -1.772 to -0.950]), statistical autocorrelation was excluded (in a subset of 20 patients with repeat metabolic investigations), and the surrogate remained valid in different subgroups of transplant recipients.

Our surrogate "HOMA(sec)xMcAuley's index," requiring only fasting glucose, insulin, and triglycerides, is a simple and noninvasive surrogate for the DI. Its predictive utility for identifying impending hyperglycemia posttransplantation should be investigated further to ascertain whether its experimental nature can translate to clinical validity.