Risk Factors Associated With the Onset and Progression of Posttransplantation Diabetes in Renal Allograft Recipients

Abstract

OBJECTIVE -The aim of this study was to assess the incidence of posttransplantation diabetes mellitus (PTDM) in renal allograft recipients and to investigate factors contributing to the onset and progression of PTDM and its underlying pathogenic mechanism(s).RESEARCH DESIGN AND METHODS -A total of 77 patients with normal glucose tolerance (NGT) were enrolled in this study. An oral glucose tolerance test was performed 1 week before transplantation and repeated at 1 and 7 years after transplantation.RESULTS -The overall incidence of PTDM was 39% at 1 year and 35.1% at 7 years posttransplantation. The incidence for each category of PTDM was as follows: persistent PTDM (P-PTDM) (patients who developed diabetes mellitus within 1 year of transplantation and remained diabetic during 7 years), 23.4%; transient PTDM (T-PTDM) (patients who developed diabetes mellitus during the 1st year after transplantation but eventually recovered to have NGT), 15.6%; late PTDM (L-PTDM) (patients who developed diabetes mellitus later than 1 year after transplantation), 11.7%; and non-PTDM during 7 years (N-PTDM 7 ) (patients who did not develop diabetes mellitus during 7 years), 49.3%. Older age (Ն40 years) at transplantation was a higher risk factor for P-PTDM, whereas a high BMI (Ն25 kg/m 2 ) and impaired fasting glucose (IFG) at 1 year posttransplantation were higher risk factors for L-PTDM. Impaired insulin secretion rather than insulin resistance was significantly associated with the development of Pand L-PTDM.CONCLUSIONS -Impaired insulin secretion may be the main mechanism for the development of PTDM. Older age at transplantation seems to be associated with P-PTDM, whereas a high BMI and IFG at 1 year after transplantation were associated with L-PTDM. Diabetes Care 30:609 -615, 2007P osttransplantation diabetes mellitus (PTDM) is a major complication after kidney transplantation and can lead to a wide range of complications including graft loss, increased mortality, increased number of rejections, and increased risk of cardiovascular disease (1-4). A recent meta-analysis of observational studies and randomized, controlled trials showed that the incidence of PTDM during the 1st year after transplantation varied from 2 to 50% (5). There have been several previous reports on PTDM in Korean patients, albeit for a short period of observation. We reported previously that the incidence of PTDM was 23.7% in 114 patients treated with cyclosporine A (CsA) at 9 -12 months after transplantation (6), whereas Cho et al. (7) reported that it was 57.1% in 21 patients treated with tacrolimus at 6 months after transplantation in Korea.PTDM and type 2 diabetes are similar in many ways. One example is that the onset of both can be insidious (8); individuals may experience glucose intolerance and remain asymptomatic for years before symptoms manifest clinically (9,10). Furthermore, PTDM is not always permanent and may resolve within weeks or months, sometimes without treatment (11). Although several recent reports on a consensus definition of PTDM ha...

A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients

“…The rest of the patients were assigned to the nonposttransplantation diabetic group. According to our previous study (15), cases of persistent PTDM (patients who developed diabetes within 1 year posttransplantation and remained diabetic) and late PTDM (patients who developed diabetes after 1 year posttransplantation) were assigned to the posttransplantation diabetic group. Transient PTDM cases (patients who developed diabetes within 1 year posttransplantation but eventually recovered to normoglycemia without medication) were classified as non-PTDM.…”

“…Although many studies have reported that insulin resistance is important to the pathophysiology of PTDM, a defect in insulin secretion may also play a role in the development of PTDM (10,15). Insulin is stored in pancreatic ␤-cells as zinc-insulin crystals.…”

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion

“…Disturbance of insulin secretion has been suggested to be a pathophysiological event that contributes to the development of PTDM. 9,10 The role of ZnT-8 in pancreatic b-cells is also not well characterized. However, ZnT-8 is a plausible candidate factor for modification of glucose metabolism in PTDM because it was shown to colocalize with insulin vesicles in b-cells, and ablation of the gene had a negative effect on insulin secretion in animal experiments.…”

Management of Diabetes in Organ Transplant Patients

“…신장이식 환자에서도 40세 이상일 경우 이식 후 당뇨병의 발생이 증가하는 것으로 알려져 있고 [8,9], 이식 당시 나이가 60세 이상이면 젊은 사람에 비해 이식 후 당 뇨병이 2.6배 더 많이 발생한다는 보고가 있다 [10]. 또한 40세 이상의 높은 연령대는 이식 후 발생한 당뇨병이 정상 혈당으로 회복되지 않고 지속되는 중요한 고 위험 인자이 다 [11].…”

“…Calcineurin억제제는 인슐린 저항성을 증가시 키는 부분도 있지만 췌장의 베타세포에 독성을 나타내어 인슐린 분비능을 저하시킴으로써 혈당을 상승시키는 부분 이 더 중요할 수 있다 [31]. 본 연구진이 7년간 추적관찰한 결과 한국인 신장이식환자에서는 인슐린 분비 결함이 인 슐린저항성의 증가보다 이식 후 당뇨병 발병에 더 중요한 다는 결과를 얻어 보고한바 있다 [11].…”