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.

Posttransplant diabetes mellitus (PTDM) and prediabetes represent serious complications after kidney transplantation and are associated with increased cardiovascular morbidity and mortality. We assessed the predictive performance of continuous glucose monitoring (CGM) compared with plasma glucose and hemoglobin A1c in 46 kidney transplant recipients (KTRs) without known preexisting diabetes mellitus. CGM (14-day recording duration) was performed on days 8, 30, 45, 60, 90, and 180 posttransplant. Eight patients (17%) developed PTDM and nine (20%) impaired glucose tolerance (IGT), as diagnosed by oral glucose tolerance test (oGTT)-derived 2-hour plasma glucose (2hPG) or glucose-lowering therapy on day 90. CGM-readouts percent of time >140 mg/dL (%TAR (140 mg/dL)) and percent of time >180 mg/dL (%TAR (180 mg/dL)) showed excellent in-sample test characteristics regarding PTDM from day 8 onward (days 8-90 receiver operating characteristic area under the curve: 0.88-0.99) and regarding PTDM/IGT with the commencement of maintenance immunosuppression from day 30 onward (days 30-90 receiver operating characteristic area under the curve: 0.88-0.91). Exploratory CGM-%TAR (140 mg/dL)-screening thresholds of 31.8% on day 8 and 13.2% on day 30 yielded sensitivities/specificities of 88%/83% for PTDM and 94%/78% for PTDM/IGT on day 90, respectively. Although our findings need to be replicated in studies with larger sample sizes, CGM bears promising potential to facilitate clinical practice and research regarding PTDM.

International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Assessment of bioimpedance spectroscopy devices: a comparative study and error analysis of gold-plated copper electrodes.

Objective. Bioimpedance spectroscopy (BIS) is a non-invasive diagnostic tool to derive fluid volume compartments from frequency dependent voltage drops in alternating currents by extrapolating to the extracellular resistance (R0) and intracellular resistance (Ri). Here we tested whether a novel BIS device with reusable and adhesive single-use electrodes produces results which are (in various body positions) equivalent to an established system employing only single-use adhesive electrodes.Approach. Two BIS devices ('Cella' and the 'Body Composition Monitor' [BCM]) were compared using four dedicated resistance testboxes and by measuring 40 healthy volunteers.Invivocomparisons included supine wrist-to-ankle (WA) reference measurements and wrist-to-wrist (WW) measurements with pre-gelled silver/silver-chloride (Ag/AgCl) electrodes and WW measurements with reusable gold-plated copper electrodes.Main results. Coefficient of variation were <1% for all testbox measurements with both BIS devices. Accuracy was within ±1% of true resistance variability, a threshold which was only exceeded by the Cella device for all resistances in a testbox designed with a lowR0/Riratio.Invivo, WA-BIS differed significantly between BIS devices (p< 0.001). Reusable WW electrodes exhibited larger resistances than WW-BIS with Ag/AgCl electrodes (R0: 738.36 and 628.69 Ω;Ri: 1508.18 and 1390 Ω) and the relative error varied from 7.6% to 31.1% (R0) and -15.6% to 37.3% (Ri).Significance. Both BIS devices produced equivalent resistances measurements but different estimates of body composition bothinsilicoand in WA setupsinvivo, suggesting that the devices should not be used interchangeably. Employing WW reusable electrodes as opposed to WA and WW measurement setups with pre-gelled Ag/AgCl electrodes seems to be associated with measurement variations that are too large for safe clinical use. We recommend further investigations of measurement errors originating from electrode material and current path.

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

Posttransplant diabetes mellitus (PTDM) is a common complication after kidney transplantation. Pathophysiologically, whether beta-cell dysfunction rather than insulin resistance may be the predominant defect in PTDM has been a matter of debate. The aim of the present analysis was to compare glucometabolism in kidney transplant recipients with and without PTDM. To this aim, we included 191 patients from a randomized controlled trial who underwent oral glucose tolerance tests (OGTTs) 6 months after transplantation. We derived several basic indices of beta-cell function and insulin resistance as well as variables from mathematical modeling for a more robust beta-cell function assessment. Mean ± standard deviation of the insulin sensitivity parameter PREDIM was 3.65 ± 1.68 in PTDM versus 5.46 ± 2.57 in NON-PTDM. Model-based glucose sensitivity (indicator of beta-cell function) was 68.44 ± 57.82 pmol∙min-1∙m-2∙mM-1 in PTDM versus 143.73 ± 112.91 pmol∙min-1∙m-2∙mM-1 in NON-PTDM, respectively. Both basic indices and model-based parameters of beta-cell function were more than 50% lower in patients with PTDM, indicating severe beta-cell impairment. Nonetheless, some defects in insulin sensitivity were also present, although less marked. We conclude that in PTDM, the prominent defect appears to be beta-cell dysfunction. From a pathophysiological point of view, patients at high risk for developing PTDM may benefit from intensive treatment of hyperglycemia over the insulin secretion axis.

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

Rationale & Objectives: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia. Study Design: Open-label randomized parallel 3-arm design. Settings & Participants: In total, 85 kidney transplant recipients without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin, or control. Interventions: Insulin was to be initiated at afternoon capillary blood glucose level of ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose level of ≥200 mg/dL (11.1 mmol/L; control). Outcomes: Hemoglobin A1c (HbA1c) levels at 3 months post-transplant (primary endpoint). PTDM assessed using oral glucose tolerance test at 12 and 24 months. Results: CSII therapy lasted until median day 18 and maximum day 88. The median HbA1c value at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (P = 0.70) and 5.4% (36 mmol/mol) in the basal insulin group (P = 0.02). At months 12 and 24, the odds for PTDM were similar compared with the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group (0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups. Limitations: This study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol, and concerns regarding reliability of HbA1c measurements. Conclusions: CSII therapy was not superior at reducing HbA1c levels at month 3 or PTDM prevalence at months 12 and 24 compared with the control or basal insulin group.

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

Post-transplant diabetes mellitus (PTDM) is a frequent complication after kidney transplantation (KT). This systematic review investigated the effect of different immunosuppressive regimens on the risk of PTDM. We performed a systematic literature search in MEDLINE and CENTRAL for randomized controlled trials (RCTs) that included KT recipients with any immunosuppression and reported PTDM outcomes up to 1 October 2023. The analysis included 125 RCTs. We found no differences in PTDM risk within induction therapies. In de novo KT, there was an increased risk of developing PTDM with tacrolimus versus cyclosporin (RR 1.71, 95%CI [1.38-2.11]). No differences were observed between tacrolimus+mammalian target of rapamycin inhibitor (mTORi) and tacrolimus+MMF/MPA, but there was a tendency towards a higher risk of PTDM in the cyclosporin+mTORi group (RR 1.42, 95%CI [0.99-2.04]). Conversion from cyclosporin to an mTORi increased PTDM risk (RR 1.89, 95%CI [1.18-3.03]). De novo belatacept compared with a calcineurin inhibitor resulted in 50% lower risk of PTDM (RR 0.50, 95%CI [0.32-0.79]). Steroid avoidance resulted in 31% lower PTDM risk (RR 0.69, 95%CI [0.57-0.83]), whereas steroid withdrawal resulted in no differences. Immunosuppression should be decided on an individual basis, carefully weighing the risk of future PTDM and rejection.