Insulin Resistance after Renal Transplantation

Midtvedt, Karsten; Hjelmesæth, Jøran; Hartmann, Anders; Lund, K; Paulsen, Dag; Egeland, Thore; Jenssen, Trond

doi:10.1097/01.asn.0000145435.80005.1e

Cited by 166 publications

(100 citation statements)

References 39 publications

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“…Among immunosuppressants, steroids have long been recognized to potently affect glucose tolerance by a prevalent increase of peripheral insulin resistance. However, daily prednisone doses as low as 5 mg, as in the patients studied here, may not influence insulin sensitivity at all (8). CNI seem to have a different diabetogenic mechanism from steroids, with dysfunctional insulin release being more prominent than insulin resistance (5,28 -30).…”

Section: Discussionmentioning

confidence: 94%

“…In the analysis performed by Montori et al (3), the type of immunosuppressive regimen used was found to explain 74% of the variability in incidence, with high-dose steroids being associated with the highest incidences. Aside from steroids (8), the calcineurin inhibitors (CNI) are associated with an increased risk for diabetes after transplantation, the risk being higher for tacrolimus than for cyclosporine A (CsA) (3,4,9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Glucose Metabolism in Renal Transplant Recipients

Teutonico

Schena²,

Paolo³

2005

Journal of the American Society of Nephrology

227

151

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Cyclosporine A (CsA) and tacrolimus have been associated with an increased risk for diabetes after transplantation, whereas sirolimus is deemed to be devoid of any effect on glucose metabolism. This study was performed to investigate the effect of the withdrawal of calcineurin inhibitors and the switch to sirolimus on peripheral insulin resistance and pancreatic ␤ cell response. Twenty-six patients who received a kidney transplant and discontinued CsA and were converted to sirolimus and 15 recipients of suboptimal kidneys who were treated with tacrolimus plus sirolimus for the first 3 mo after grafting and thereafter with sirolimus alone were enrolled. All patients underwent an oral glucose tolerance test and intravenous insulin tolerance test before and 6 mo after the conversion to sirolimus-alone therapy. The withdrawal of CsA or tacrolimus was associated with a significant fall of insulin sensitivity (both P ‫؍‬ 0.01) and with a defect in the compensatory ␤ cell response, as measured by the disposition index (P ‫؍‬ 0.004 and P ‫؍‬ 0.02, respectively). The increase of insulin resistance and the decrease of disposition index significantly correlated with the change of serum triglyceride concentration after the conversion to sirolimus-based therapy (R 2 ‫؍‬ 0.30, P ‫؍‬ 0.0002; and R 2 ‫؍‬ 0.19, P ‫؍‬ 0.004, respectively). Clinically, the switch to sirolimus was associated with a 30% increase of incidence of impaired glucose tolerance and with four patients' developing new-onset diabetes. In conclusion, the discontinuation of calcineurin inhibitors and their replacement by sirolimus fail to ameliorate the glycometabolic profile of kidney transplant recipients. Rather, it is associated with a worsening of insulin resistance and an inappropriately low insulin response.

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Glucose Metabolism in Renal Transplant Recipients

Teutonico

Schena²,

Paolo³

2005

Journal of the American Society of Nephrology

227

151

View full text Add to dashboard Cite

show abstract

“…In view of the widely known adverse effect of steroids on IS, glucose tolerance, and lipid profile (10,11,16,18), the positive relationship between glucocorticoid dose and adiponectin concentration may seem unexpected and difficult to explain. However, a number of previous studies support a possible positive relationship between steroids and adiponectin both in humans (5,40,41) and in rodents (42).…”

Section: Immunosuppressive Drugs and Adiponectinmentioning

confidence: 99%

“…This may be explained partly by immunosuppressive therapy (10), in particular steroids (11). Inhibition of endogenous calcineurin activity with tacrolimus or cyclosporine A (CsA) may lead to enhanced adipogenesis, which may explain the metabolic disturbances that are associated with these drugs (12).…”

mentioning

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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“…Single-center studies have demonstrated that oral prednisolone dose reduction to 5 mg daily significantly improves glucose tolerance during the first year after transplantation (Hjelmesaeth et al, 1997) while a 0.01 mg/kg/day increase in prednisolone dose is associated with a 5% risk of developing NODAT (Hjelmesaeth et al, 2001). In a small study involving 57 stable renal transplant recipients, Midtvedt and colleagues found that prednisolone dose reduction from a mean of 16 mg daily (range 10 to 30) to 9 mg (range 5 to 12.5) resulted in an average increase in insulin sensitivity index of 24% (Midtvedt et al, 2004). However, complete withdrawal of 5 mg/day of prednisolone did not influence insulin sensitivity significantly.…”

Section: Modifiable Risk Factors 421 Corticosteroid-associated Nodatmentioning

confidence: 99%