Insulin Resistance and Insulin Deficiency in the Pathogenesis of Posttransplantation Diabetes in Man

Ekstrand, Agneta; Eriksson, Jerry; Grönhagen-Riska, C; Ahonen, Pekka; Groop, L.

doi:10.1097/00007890-199203000-00014

Cited by 136 publications

(87 citation statements)

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“…One study demonstrated that even normoglycemic transplant recipients on steroids are insulin resistant compared to controls from the general population (27). In contrast, another study showed that treatment with tacrolimus decreases insulin release, but does not affect insulin resistance (28).…”

Section: Discussionmentioning

confidence: 99%

New-Onset Diabetes After Transplantation:Results From a Double-Blind Early Corticosteroid Withdrawal Trial

Pirsch

Henning

First

et al. 2015

American Journal of Transplantation

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New-onset diabetes after transplantation (NODAT) is an important complication following kidney transplantation. Data from the 5-year early steroid withdrawal double-blind randomized trial were analyzed to determine if steroid avoidance reduced the NODAT risk. Incidence, timing and risk factors for NODAT were evaluated using eight definitions. By American Diabetes Association definition, 36.3% of patients on chronic corticosteroids (CCS) and 35.9% on early corticosteroid withdrawal (CSWD) were diagnosed with NODAT by 5 years. The definition combining fasting blood glucose !126 mg/dL on two occasions or treatment identified slightly more cases of NODAT: CCS (39.3%) and CSWD (39.4%). Through 5 years posttransplant, the proportion of NODAT patients requiring treatment were similar (CSWD 22.5% vs. CCS 21.5%); however, insulin therapy was lower with CSWD (3.7% vs. 11.6%; p ¼ 0.049). By multivariate analysis, only age, but not corticosteroid use, was a significant risk factor for NODAT for more than one definition. Numerical, but not statistically significant trends toward lower NO-DAT rates with CSWD were observed through 5 years for insulin use, HbA1c !6.0% and !6.5% on two occasions. This prospective, randomized trial of CSWD indicates that CSWD has a limited impact in reducing NODAT when compared to low-dose prednisone (5 mg/day from month 6 to 5 years).

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Section: Discussionmentioning

confidence: 99%

New-Onset Diabetes After Transplantation:Results From a Double-Blind Early Corticosteroid Withdrawal Trial

Pirsch

Henning

First

et al. 2015

American Journal of Transplantation

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“…Calcineurin inhibitors probably impair insulin release, and steroids may have negative effects on insulin action and secretion [12,13,14,15,16]. In this respect, PTDM shares features with both Type 1 and Type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

Asymptomatic cytomegalovirus infection is associated with increased risk of new-onset diabetes mellitus and impaired insulin release after renal transplantation

et al. 2004

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Aims/hypothesis. The human cytomegalovirus (CMV) may increase the risk of diabetes mellitus, but the literature is scarce. The present study was designed to test the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset diabetes after renal transplantation, and to assess the impact of asymptomatic CMV infection on OGTT-derived estimates of insulin release and insulin action. Methods. A total of 160 consecutive non-diabetic renal transplant recipients on cyclosporine (Sandimmun Neoral)-based immunosuppression were closely monitored for CMV infection during the first 3 months after transplantation. All patients underwent a 75-g OGTT at 10 weeks. Excluded from the analyses were 36 patients with symptomatic CMV infection (disease).Results. The incidence of new-onset diabetes was 6% in a control group of recipients without CMV infection (4/63) and 26% in the group with asymptomatic CMV infection (16/61). Asymptomatic CMV infection was associated with a significantly increased risk of new-onset diabetes (adjusted odds ratio: 4.00; 95% CI: 1.19 to 13.43, p=0.025). The group of patients with CMV infection had a significantly lower median insulin release than controls. Conclusions/interpretation. Our findings support the hypothesis that asymptomatic CMV infection is associated with increased risk of new-onset post-transplant diabetes mellitus, and suggest that impaired insulin release may involve one pathogenetic mechanism.

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“…Renal transplant recipients are insulin resistant when compared with age-and gender-matched control subjects (9). This may be explained partly by immunosuppressive therapy (10), in particular steroids (11).…”

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confidence: 99%

Hypoadiponectinemia Is Associated with Insulin Resistance and Glucose Intolerance after Renal Transplantation

Hjelmesæth

Flyvbjerg²,

Jenssen³

et al. 2006

Clinical Journal of the American Society of Nephrology

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The objectives of this analysis were (1) to assess whether low serum adiponectin concentrations are associated with insulin resistance, metabolic syndrome, and new-onset posttransplantation diabetes mellitus (PTDM) and (2) to examine the possible effects of immunosuppressive and antihypertensive therapies on circulating adiponectin levels after renal transplantation. A total of 172 consecutive previously nondiabetic renal transplant recipients were examined 3 mo after transplantation, the majority (n ‫؍‬ 167) with an oral glucose tolerance test. Serum adiponectin was measured by an in-house time-resolved immunofluorometric assay. Insulin secretion and insulin sensitivity were estimated by previously validated oral glucose tolerance test-derived indexes. One-and 6-yr follow-up data were available in subgroups of patients. Lower adiponectin levels were significantly associated with insulin resistance but not with insulinopenia. Patients with low adiponectin levels (first quartile) had significantly higher odds of PTDM (odds ratio [OR] 3.6; 95% confidence interval [CI] 1.1 to 12.7; P ‫؍‬ 0.049) and metabolic syndrome (OR 3.9; 95% CI 1.6 to 9.5; P ‫؍‬ 0.003) than patients in the upper (fourth) quartile. The increased risk for PTDM in patients with low adiponectin levels remained significant after adjustment for age, steroid dose, and family history of diabetes. Treatment with ␤ blockers was independently associated with lower serum adiponectin levels, and total steroid dose was associated with higher serum adiponectin levels. Low baseline adiponectin levels were also associated with significantly higher odds of PTDM at 6 yr (OR 6.9; 95% CI ‫؍‬ 1.1 to 41.8; P ‫؍‬ 0.037). Serum adiponectin levels correlate with posttransplantation insulin sensitivity and glucose tolerance. Glucocorticoids and ␤ blockers seem to have opposite effects on circulating adiponectin levels.

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Insulin Resistance and Insulin Deficiency in the Pathogenesis of Posttransplantation Diabetes in Man

Cited by 136 publications

References 0 publications

New-Onset Diabetes After Transplantation:Results From a Double-Blind Early Corticosteroid Withdrawal Trial

New-Onset Diabetes After Transplantation:Results From a Double-Blind Early Corticosteroid Withdrawal Trial

Asymptomatic cytomegalovirus infection is associated with increased risk of new-onset diabetes mellitus and impaired insulin release after renal transplantation

Hypoadiponectinemia Is Associated with Insulin Resistance and Glucose Intolerance after Renal Transplantation

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