Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients

Ammon Handisurya, Corinna Kerscher, Andrea Tura, Harald Herkner, Berit Anna Payer, Mattias Mandorfer, Johannes Werzowa, Wolfgang Winnicki, Thomas Reiberger, Alexandra Kautzky-Willer, Giovanni Pacini, Marcus Säemann, Alice Schmidt, Ammon Handisurya, Corinna Kerscher, Andrea Tura, Harald Herkner, Berit Anna Payer, Mattias Mandorfer, Johannes Werzowa, Wolfgang Winnicki, Thomas Reiberger, Alexandra Kautzky-Willer, Giovanni Pacini, Marcus Säemann, Alice Schmidt

Abstract

Background: Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients.

Methods: In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR).

Results: After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression.

Conclusions: HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen.

Trial registration: ClinicalTrials.gov NCT02108301.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Trend flow chart.
Fig 1. Trend flow chart.
Fig 2. Metabolic parameters before and three…
Fig 2. Metabolic parameters before and three months after conversion.
Determination of plasma glucose (A), serum insulin (B) and C-peptide (C) levels by OGTTs performed prior to (full symbols) and three months after (blank symbols) the conversion from taxrolimus to cyclosporine A. Data are expressed as median (IQR). + indicates p

Fig 3. Correlation analyses.

Scatter plots showing…

Fig 3. Correlation analyses.

Scatter plots showing the correlation between tacrolimus trough levels and fasting…

Fig 3. Correlation analyses.
Scatter plots showing the correlation between tacrolimus trough levels and fasting insulin levels before conversion from tacrolimus to cyclosporine A.
Fig 3. Correlation analyses.
Fig 3. Correlation analyses.
Scatter plots showing the correlation between tacrolimus trough levels and fasting insulin levels before conversion from tacrolimus to cyclosporine A.

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