Posttransplant Diabetes Mellitus (PTDM)

The study of posttransplant diabetes mellitus (PTDM) is a primary focus of the HD & Co Research Group. At the Medical University of Vienna, the first projects and research ideas in this area started in the year 2007 under the leadership of Marcus Säemann and primarily involved our former colleagues Johannes Werzowa and Michael Haidinger, besides Manfred Hecking.

Marcus Säemann’s idea was that we should turn around the ‘watch-and-wait-for-diabetes-to-develop’ approach which was guideline-conform at that time (see PMID 12775942 for the previous consensus guidelines). Together, we found with very limited academic funding (Astellas grant for the TIP-study, see below), that basal insulin, initiated early against postoperative hyperglycemia can indeed decrease overt diabetes at 1 year post-transplant (Hecking, Haidinger et al., 2012).

The study attracted considerable attention, and inspired Akinlolu Ojo and Fu Luan (both working at the University of Michigan at that time) to submit an R01 research grant to the NIDDK, based on this idea (see below). The grant was approved and allowed conducting the ITP-NODAT study (ClinicalTrials.gov Identifier NCT03507829), involving 263 patients at 4 European centers.

Elisabeth Schwaiger, together with Amelie Kurnikowski, Simon Krenn, Leon Bergfeld, Alexander Frey, David Topitz and Michael Bergmann took on the tremendous work of retrieving all the study results from our collaborating partners (Hospital Del Mar in Barcelona [Julio Pascual], Charité Berlin [Klemens Budde], Medical University of Graz [Alexander Rosenkranz, Kathrin Eller]).

The final product of this study was an extensive analysis and will be published soon (the manuscript was allowed re-submission at JASN); an Abstract presentation at the European Association for the Study of Diabetes (EASD) from the year 2020, summarizing the ITP-NODAT study results, can be accessed here: Early postoperative basal insulin therapy for the prevention of post-transplant diabetes onset after kidney transplantation (ITP-NODAT) - Virtual Meeting | EASD.

We are deeply indebted to our great collaborators at the three centers above, and we thank C. Rodriguez-Torres for monitoring the trial.

We also heartfully thank Marcus Säemann for igniting this entire study idea and formally overseeing the trial through the year 2016. An important aspect of this study is funding: grants from Astellas and Eli/Lilly, besides the grant from NIDDK (see below).

Different studies:

vildaglitpin (Haidinger, Werzowa et al., 2014, Haidinger, Werzowa et al., 2010),
vidagliptin and pioglitazone (Werzowa, Hecking et al., 2013),
empagliflozin (Schwaiger, Burghart et al., 2019).

Pathophysiological studies:

insulin secretion versus insulin resistance (Hecking, Kainz et al., 2013a, Muller, Schwaiger et al., 2020), clamp-derived insulin sensitivity (Tura, Chemello et al., 2018).

Letters and commentaries:

(Bergfeld, Werzowa et al., 2018, Hecking, Sharif et al., 2013b)

Reviews:

(Hecking, Sharif et al., 2021, Hecking, Werzowa et al., 2013c, Werzowa, Hecking et al., 2015a, Werzowa, Saemann et al., 2015c)

Consensus meeting:

The term NODAT was later changed back to PTDM at a Vienna-based consensus meeting (Sharif, Hecking et al., 2014).

PUBLICATIONS

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation.

Haidinger M, Werzowa J, Voigt HC, Pleiner J, Stemer G, Hecking M, Döller D, Hörl WH, Weichhart T, Säemann MD

Analysis of liver function in renal transplant recipients undergoing C2-monitoring for cyclosporine.

Hecking M, Kainz A, Schillinger M, Posch C, Birsan T, Rasoul-Rockenschaub S, Böhmig GA, Schmaldienst S, Watschinger B, Hörl WH, Mühlbacher F, Säemann MD

Proceedings from an international consensus meeting on posttransplantation diabetes mellitus: recommendations and future directions.

Sharif A, Hecking M, de Vries AP, Porrini E, Hornum M, Rasoul-Rockenschaub S, Berlakovich G, Krebs M, Kautzky-Willer A, Schernthaner G, Marchetti P, Pacini G, Ojo A, Takahara S, Larsen JL, Budde K, Eller K, Pascual J, Jardine A, Bakker SJ, Valderhaug TG,

Antidiabetic therapy in post kidney transplantation diabetes mellitus.

Werzowa J, Säemann M, Haidinger M, Krebs M, Hecking M

Efficacy and safety of vildagliptin in new-onset diabetes after kidney transplantation--a randomized, double-blind, placebo-controlled trial.

Haidinger M, Werzowa J, Hecking M, Antlanger M, Stemer G, Pleiner J, Kopecky C, Kovarik JJ, Döller D, Pacini G, Säemann MD

The diagnosis of posttransplantation diabetes mellitus: meeting the challenges.

Werzowa J, Hecking M, Haidinger M, Döller D, Sharif A, Tura A, Säemann MD

Comparison of glycemic control and variability in patients with type 2 and posttransplantation diabetes mellitus.

Werzowa J, Pacini G, Hecking M, Fidler C, Haidinger M, Brath H, Thomas A, Säemann MD, Tura A

Assessment of beta-cell function and insulin secretion in subjects that underwent renal transplantation.

Tura A, Hecking M, Wolzt M, Saemann MD, Pacini G

Early basal insulin therapy decreases new-onset diabetes after renal transplantation.

Hecking M, Haidinger M, Döller D, Werzowa J, Tura A, Zhang J, Tekoglu H, Pleiner J, Wrba T, Rasoul-Rockenschaub S, Mühlbacher F, Schmaldienst S, Druml W, Hörl WH, Krebs M, Wolzt M, Pacini G, Port FK, Säemann MD

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation.

Haidinger M, Werzowa J, Voigt HC, Pleiner J, Stemer G, Hecking M, Döller D, Hörl WH, Weichhart T, Säemann MD

Clinical trials for treatment of NODAT: time to collaborate.

Sharif A, de Vries AP, Porrini E, Hecking M, Saemann M,

Novel views on new-onset diabetes after transplantation: development, prevention and treatment.

Hecking M, Werzowa J, Haidinger M, Hörl WH, Pascual J, Budde K, Luan FL, Ojo A, de Vries AP, Porrini E, Pacini G, Port FK, Sharif A, Säemann MD,

Vildagliptin and pioglitazone in patients with impaired glucose tolerance after kidney transplantation: a randomized, placebo-controlled clinical trial.

Werzowa J, Hecking M, Haidinger M, Lechner F, Döller D, Pacini G, Stemer G, Pleiner J, Frantal S, Säemann MD

Glucose metabolism after renal transplantation.

Hecking M, Kainz A, Werzowa J, Haidinger M, Döller D, Tura A, Karaboyas A, Hörl WH, Wolzt M, Sharif A, Roden M, Moro E, Pacini G, Port FK, Säemann MD

Comment on: Chakkera et al. Can new-onset diabetes after kidney transplant be prevented? Diabetes Care 2013;36:1406-1412.

Hecking M, Sharif A, Port FK, Säemann MD

Glucose Metabolism After Kidney Transplantation: Insulin Release and Sensitivity With Tacrolimus- Versus Belatacept-Based Immunosuppression.

Müller MM, Schwaiger E, Kurnikowski A, Haidinger M, Ristl R, Tura A, Pacini G, Werzowa J, Hecking M

Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics.

Hecking M, Sharif A, Eller K, Jenssen T

Cardiovascular events associate with diabetes status rather than with early basal insulin treatment for the prevention of post-transplantation diabetes mellitus.

Topitz D, Schwaiger E, Frommlet F, Werzowa J, Hecking M

A randomized controlled trial-based algorithm for insulin-pump therapy in hyperglycemic patients early after kidney transplantation.

Werzowa JM, Säemann MD, Mohl A, Bergmann M, Kaltenecker CC, Brozek W, Thomas A, Haidinger M, Antlanger M, Kovarik JJ, Kopecky C, Song PXK, Budde K, Pascual J, Hecking M

Correspondence regarding the impact of kidney transplantation on insulin sensitivity.

Bergfeld L, Werzowa J, Säemann M, Hecking M

Empagliflozin in posttransplantation diabetes mellitus: A prospective, interventional pilot study on glucose metabolism, fluid volume, and patient safety.

Schwaiger E, Burghart L, Signorini L, Ristl R, Kopecky C, Tura A, Pacini G, Wrba T, Antlanger M, Schmaldienst S, Werzowa J, Säemann MD, Hecking M

Considerations for SGLT2 inhibitor use in post-transplantation diabetes.

Hecking M, Jenssen T

Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial.

Kurnikowski A, Nordheim E, Schwaiger E, Krenn S, Harreiter J, Kautzky-Willer A, Leutner M, Werzowa J, Tura A, Budde K, Eller K, Pascual J, Krebs M, Jenssen TG, Hecking M

Corrigendum to 'Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial' [American Journal of Transplantation 22 (2022)2880-2891].

Kurnikowski A, Nordheim E, Schwaiger E, Krenn S, Harreiter J, Kautzky-Willer A, Leutner M, Werzowa J, Tura A, Budde K, Eller K, Pascual J, Krebs M, Jenssen TG, Hecking M

Continuous glucose monitoring for the prediction of posttransplant diabetes mellitus and impaired glucose tolerance on day 90 after kidney transplantation-A prospective proof-of-concept study.

Eleftheriadis G, Naik MG, Osmanodja B, Liefeldt L, Choi M, Halleck F, Schrezenmeier E, Eckardt KU, Pigorsch M, Tura A, Kurnikowski A, Hecking M, Budde K

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial.

Kurnikowski A, Werzowa J, Hödlmoser S, Krenn S, Paschen C, Mussnig S, Tura A, Harreiter J, Krebs M, Song PXK, Eller K, Pascual J, Budde K, Hecking M, Schwaiger E

Immunosuppressive drug combinations after kidney transplantation and post-transplant diabetes: A systematic review and meta-analysis.

Oliveras L, Coloma A, Lloberas N, Lino L, Favà A, Manonelles A, Codina S, Couceiro C, Melilli E, Sharif A, Hecking M, Guthoff M, Cruzado JM, Pascual J, Montero N

Glucometabolism in Kidney Transplant Recipients with and without Posttransplant Diabetes: Focus on Beta-Cell Function.

Kurnikowski A, Salvatori B, Krebs M, Budde K, Eller K, Pascual J, Morettini M, Göbl C, Hecking M, Tura A

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial.

Schwaiger E, Krenn S, Kurnikowski A, Bergfeld L, Pérez-Sáez MJ, Frey A, Topitz D, Bergmann M, Hödlmoser S, Bachmann F, Halleck F, Kron S, Hafner-Giessauf H, Eller K, Rosenkranz AR, Crespo M, Faura A, Tura A, Song PXK, Port FK, Pascual J, Budde K, Ristl R,

ALL PUBLICATIONS

GRANTS

2008 - 2010

Treat-to-target trial of basal insulin in post-transplant hyperglycemia (TIP): efficacy and safety of a novel protocol in renal transplant recipients receiving a tacrolimus-based immunosuppression.

Proposal written by: Manfred Hecking
Amount granted: € 49.500

by: Astellas

2009 - 2010

Transplant-Associated Hyperglycemia (TAHG): An Exploratory Study.

Proposal written by: Manfred Hecking
Amount granted: € 7.200,–

by: Takeda

2010 - 2020

Insulin Therapy for the Prevention of New-Onset Diabetes after Transplantation (ITP-NODAT).

Proposal written by: Manfred Hecking, Marcus Säemann
Amounts granted: € 311.012

by: NIH-NIDDK via University of Michigan

2012 - 2020

Sensor-Augmented Insulin Pump Therapy against Post-transplant Hyperglycemia: A Semi-Closed Loop System to Prevent New-Onset Diabetes after Renal Transplantation.