Is HLA-DR6 a Protective Factor Against Posttransplantation Diabetes Mellitus?

Abstract

Background Posttransplant diabetes mellitus (PTDM) has several pre- and posttransplant risk factors. Methods The incidence and risk factors of PTDM were retrospectively evaluated in 2117 kidney allograft recipients from June 1984 to March 2004. Type and dosage of immunosuppressive agents, pretransplant weight and human leukocyte antigen (HLA) phenotypes in PTDM patients were compared with 61 matched controls. Results Sixty-one cases (2.8%) developed PTDM requiring insulin or oral hypoglycemic therapy, out of which 47.5% were men and 52.5% were women, although only 35% of our overall recipients are women. Onset occurred at a mean of 489 days following transplantation. Patients receiving more than 15 mg/d prednisolone developed PTDM more often than those on less than 15 mg/d ( P = .000). Similarly PTDM was more frequent among patients who received more than 300 mg/d cyclosporine compared with those on less than 300 mg/d ( P = .015). Mean weight in PTDM cases and controls was 65 ± 13.4 kg and 57 ± 13.6 kg, respectively ( P = .005). HLA-DR6 was observed in 12.2% of nonaffected subjects but in none of the PTDM group ( P = .002). Conversely, HLA-DR8 was seen only in PTDM patients ( P = .012). In addition HLA-A26 was more common among PTDM patients ( P = .02) and HLA-DR52 more frequent in nonaffected subjects ( P = .025). Conclusion Our findings suggest that female sex, dosages of prednisolone and cyclosporine, pretransplant weight, and genetic factors are associated with an increased risk of PTDM. The rate of PTDM appeared to be independent of weight gain in the first year posttransplant. Protection against PTDM may be afforded by HLA-DR6 and possibly HLA-DR52. Conversely and higher incidence of diabetes has been associated with HLA-DR8 and HLA-A26.