??-Cell Dysfunction Rather Than Insulin Resistance Is the Main Contributing Factor for the Development of Postrenal Transplantation Diabetes Mellitus

Nam, J. H.; Mun, Junwon; Kim, S. I.; Kang, Sun Woo; Choi, Kyu Hun; Park, Kwangwoo; Ahn, Chul Woo; S., B.; Song, Young Duk; Lim, Shin-Il; Kim, K. R.; Lee, Hyun Chul; Huh, Kap Bum

doi:10.1097/00007890-200105270-00011

Cited by 155 publications

(113 citation statements)

References 35 publications

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“…The VDR polymorphism is also reported to affect insulin secretion (30 -32). Their results and the results of this study are consistent with our previous reports (10,15), in that a defect in insulin secretion plays a more crucial role than increased insulin resistance in the pathogenesis of PTDM.…”

Section: Discussionsupporting

confidence: 94%

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

Kang

Kim

et al. 2008

Diabetes

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OBJECTIVE—Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients, and insulin secretory defects play an important role in the pathogenesis of PTDM. The R325W (rs13266634) nonsynonymous polymorphism in the islet-specific zinc transporter protein gene, SLC30A8, has been reported to be associated with type 2 diabetes and possibly with a defect in insulin secretion. This study investigated the association between genetic variations in the SLC30A8 gene and PTDM in renal allograft recipients. RESEARCH DESIGN AND METHODS—A total of 624 unrelated renal allograft recipients without previously diagnosed diabetes were enrolled. Rs13266634 was genotyped in the cohort, which consisted of 174 posttransplantation diabetic patients and 450 non-posttransplantation diabetic subjects. The genotyping of the SLC30A8 polymorphism was performed using real-time PCR. RESULTS—The prevalence of PTDM was 33.8% in patients carrying the R/R genotype, 26.8% in patients with the R/W genotype, and 19.8% in patients with the W/W genotype. There was a strong association between the number of W-alleles and PTDM risk reduction (P for trend = 0.007). Patients with at least one T-allele showed a decreased risk of PTDM compared with those with the R/R genotype (R/W, risk ratio [RR] 0.78, P = 0.126; W/W, RR 0.52, P = 0.007). The effect of the SLC30A8 genotype remained significant after adjustments for age, sex, body weight gain, and type of immunosuppressant (R/W, hazard ratio [HR] 0.77, P = 0.114; W/W, HR 0.58, P = 0.026). CONCLUSIONS—These data provide evidence that the SLC30A8 rs13266634 gene variation is associated with protection from the development of PTDM in renal allograft recipients.

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Section: Discussionsupporting

confidence: 94%

“…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.…”

mentioning

confidence: 99%

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

Kang

Kim

et al. 2008

Diabetes

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“…In the current study, the 39% incidence of PTDM at 1 year was very high and was even higher than the 23.7% we reported in our previous CsA-based study (6). In the previous study, we used the World Health Organization (WHO) criteria to define NGT (both FPG and 2-h postload glucose Ͻ7.8 mmol/l) and PTDM (FPG Ն7.8 mmol/l or 2-h postload glucose Ն11.0 mmol/l), whereas, in the current study, we defined NGT and PTDM according to American Diabetes Association criteria (8).…”

Section: Incidences Of Different Categories Of Ptdmcontrasting

confidence: 77%

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

Hur

Kim

et al. 2007

Diabetes Care

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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...

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“…The development and progression of PTD and its associated complications may be delayed by readily available interventions that are proved to be beneficial, such that early detection is likely to be important. IGT is also common posttransplantation with reported prevalence rates as high as 35% at 10 wk posttransplantation, 31 to 45% at 1 yr posttransplantation, and 13% at 6 yr posttransplantation (1,21,22). In the general population, asymptomatic IGT is an independent risk factor for all-cause mortality and of cardiovascular mortality in some studies (9 -11,23-25).…”

Section: Ptd and Igt In Rtrmentioning

confidence: 99%

Should an Oral Glucose Tolerance Test Be Performed Routinely in All Renal Transplant Recipients?

Armstrong

Prins

Beller

et al. 2006

Clinical Journal of the American Society of Nephrology

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Posttransplantation diabetes (PTD) contributes to cardiovascular disease and graft loss in renal transplant recipients (RTR). Current recommendations advise fasting blood glucose (FBG) as the screening and diagnostic test of choice for PTD. This study sought to determine (1) the predictive power of FBG with respect to 2-h blood glucose (2HBG) and (2) the prevalence of PTD using FBG and 2HBG compared with that using FBG alone, in prevalent RTR. A total of 200 RTR (mean age 52 yr; 59% male; median transplant duration 6.6 yr) who were >6 mo posttransplantation and had no known history of diabetes were studied. Patients with FBG <126 mg/dl (7.0 mmol/L; n ‫؍‬ 188) underwent an oral glucose tolerance test (OGTT). Receiver operating characteristic analyses evaluated the optimal level of FBG predictive of PTD (2HBG >200 mg/dl [11.1 mmol/L]) and impaired glucose tolerance (IGT; 2HBG 140 to 200 mg/dl [7.8 to 11.0 mmol/L]). An abnormal OGTT was reported in 79 (42%) nondiabetic RTR: PTD (n ‫؍‬ 22) and IGT (n ‫؍‬ 57). The optimal FBG that was predictive of PTD was 101 mg/dl (5.6 mmol/L; area under the curve 0.70; sensitivity 64%, specificity 67%, positive predictive value 20%, negative predictive value 93%). The optimal FBG that was predictive of IGT was less well defined (area under the curve 0.54). The prevalence of PTD was higher by OGTT than by FBG alone (17 versus 6%; P < 0.001). FBG may not be the optimal screening or diagnostic tool for PTD or IGT in RTR. Consideration should be given to introducing the OGTT as a routine posttransplantation investigation, although the implications of a pathologic OGTT are still to be determined in this population.

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??-Cell Dysfunction Rather Than Insulin Resistance Is the Main Contributing Factor for the Development of Postrenal Transplantation Diabetes Mellitus

Cited by 155 publications

References 35 publications

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

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

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

Should an Oral Glucose Tolerance Test Be Performed Routinely in All Renal Transplant Recipients?

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