Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

Øzbay, Lara Aygen; Møller, Niels; Juhl, Claus Bogh; Bjerre, Mette; Carstens, Jan; Rungby, Jørgen; Jørgensen, Kaj Anker

doi:10.1111/j.1365-2125.2011.04118.x

Cited by 43 publications

(32 citation statements)

References 51 publications

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“…On the other hand, new-onset diabetes after transplantation related to treatment with immunosuppressive medications is an important complication. In fact, the acute effects of intravenous calcineurin inhibitors (CsA) and TAC infusions in healthy volunteers include increased IS [22]. However, chronic use of TAC impairs insulin secretion at multiple distal sites in stimulus-secretion coupling [23].…”

Section: Discussionmentioning

confidence: 99%

Steroid Withdrawal in Pediatric Kidney Transplant Allows Better Growth, Lipids and Body Composition: A Randomized Controlled Trial

Mericq

Salas²,

Pinto³

et al. 2013

Horm Res Paediatr

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Background: Glucocorticoid immunosuppressant therapy in pediatric kidney transplant (Tx) recipients does not allow the improvement of growth after Tx. Objective: To determine the effect of early steroid withdrawal (SW) on longitudinal growth, insulin sensitivity (IS), and body composition (BC). Methods: This was a prospective, randomized, multicenter study in Tx. Insulin-like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP3), IS, and BC (DEXA/pQCT) were determined at baseline and up to 12 months after Tx. Results: A total of 30 patients were examined; 14 patients were assigned to the SW group (7 male, 7 female; 12 in Tanner stage I) and 16 patients were assigned to the steroid control (SC) group (10 male, 6 female;12 in Tanner stage I). Their chronological age was 7.8 ± 4.3 years, height was -2.3 ± 0.99 SD scores (SDS), and body mass index -0.3 ± 1.2 SDS. After 1 year, the SW group showed an increase in height SDS (+1.2 ± 0.22 vs. +0.60 ± 0.13 SDS in the SC group, p < 0.02), lower IGFBP3 (p < 0.05), cholesterol (p < 0.05), and higher high-density lipoprotein cholesterol (p < 0.05). SW patients had lower trunk fat with no differences in IS. Only in prepubertal patients, the SW group had lower glycemia (p < 0.05), very low-density lipoprotein cholesterol (p < 0.01), triglycerides (p < 0.05), triglycerides/glycemia index (TyG; p < 0.02), and better lean mass. Both groups showed an improvement in lean mass after kidney Tx. Conclusions: SW improved longitudinal growth, lipid profile, and trunk and lean fat in Tx patients. In prepubertal recipients, the decrease in TyG suggests better IS.

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Section: Discussionmentioning

confidence: 99%

Steroid Withdrawal in Pediatric Kidney Transplant Allows Better Growth, Lipids and Body Composition: A Randomized Controlled Trial

Mericq

Salas²,

Pinto³

et al. 2013

Horm Res Paediatr

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“…In 10 healthy human volunteers with normal BMI (24.7 Ϯ 0.5 kg/m 2 ), Øzbay et al (69) showed that an acute infusion of CNIs over 5 hours increased insulin sensitivity as determined by hyperinsulinemic-euglycemic clamp. A greater increase in sensitivity was observed with cyclosporine (25%) than tacrolimus (13%), but there was no change in first-phase insulin secretion or insulin pulsatility.…”

Section: Role Of Immunosuppression Agentsmentioning

confidence: 99%

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

Shivaswamy

Boerner

Larsen³

2015

Endocrine Reviews

249

203

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and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM. (Endocrine Reviews 37: 37-61, 2016)

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“…Corticosteroids, for example, induce insulin resistance in a dose-dependent manner by decreased beta-cell insulin production, increased gluconeogenesis, and decreased peripheral glucose utilization [38]. Calcineurin inhibitors inhibit insulin synthesis and secretion by pancreatic beta-cells [39]. mTOR inhibitors block B-cell proliferation, theoretically increasing the risk for diabetes, but also increases GLUT-4 signaling in insulin-responsive cells [40].…”

Section: Diabetesmentioning

confidence: 99%

An Update of Liver Transplantation for Nonalcoholic Steatohepatitis

Thomason

Charlton

2015

Curr Hepatology Rep

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Nonalcoholic steatohepatitis (NASH), obesity, and the metabolic syndrome are highly prevalent before and after liver transplantation, with NASH currently the second most common indication. This review considers established and new aspects of liver transplantation for NASH. NASH is one of many sequelae of obesity and most frequently occurs on a background of the metabolic syndrome. While recurrence of steatosis is common, recurrence of NASH with advanced stages of fibrosis is unusual, with graft loss due to recurrence of NASH cirrhosis occurring with a frequency of less than 5 %. In contrast, the components of the metabolic syndrome, which are important predictors of posttransplant outcomes, are nearly ubiquitous following liver transplantation and are exacerbated by factors such as immunosuppression. As many aspects of the metabolic syndrome are modifiable, screening for and treating complications of obesity and minimization of immunosuppression are cornerstones of optimizing outcomes for transplant recipients with NASH. The optimal approach to immunosuppression, the role of bariatric surgery, and nutritional and pharmacotherapy of NASH in liver transplant recipients are evolving rapidly. Overall, a minimalist approach to immunosuppression is advised.

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Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

Cited by 43 publications

References 51 publications

Steroid Withdrawal in Pediatric Kidney Transplant Allows Better Growth, Lipids and Body Composition: A Randomized Controlled Trial

Steroid Withdrawal in Pediatric Kidney Transplant Allows Better Growth, Lipids and Body Composition: A Randomized Controlled Trial

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

An Update of Liver Transplantation for Nonalcoholic Steatohepatitis

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